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Cancer drug shortages spur worry, rationing, and tough choices
CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.
“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.
This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”
This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.
“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.
Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.
The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients.
The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.
Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.
In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”
She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).
“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.
At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.
“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.
Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.
In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.
In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.
Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”
Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.
“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”
Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.
“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.
“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said.
She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.
Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.
“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”
Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.
The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.
“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”
Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.
Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.
On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.
In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.
As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.
However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.
“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.
In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”
Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.
“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.
CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.
“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.
This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”
This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.
“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.
Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.
The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients.
The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.
Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.
In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”
She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).
“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.
At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.
“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.
Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.
In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.
In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.
Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”
Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.
“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”
Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.
“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.
“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said.
She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.
Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.
“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”
Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.
The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.
“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”
Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.
Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.
On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.
In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.
As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.
However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.
“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.
In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”
Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.
“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.
CHICAGO – Oncologist Denise Yardley, MD, isn’t used to expressing uncertainty when she tells patients about what’s in store for them in terms of drug treatment. But things are dramatically different now amid a severe national shortage of carboplatin and cisplatin, two common and crucial cancer drugs.
“There’s a regimen I’m thinking about,” Dr. Yardley told a new patient recently, “but we’ll have to wait until you finish your staging evaluation to see whether I can deliver this. Another regimen that’s a little more toxic is my second choice.” And, she added, the alternative chemotherapy treatment – anthracycline instead of carboplatin – requires a longer treatment period.
This ambiguity is hardly ideal, said Dr. Yardley, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville. “It’s another factor in being overwhelmed in a first-time visit and wanting to know the details about what your treatment is going to look like. You’re not walking out knowing exactly what you’re going to take or the exact timing so you can start mapping out your calendar and work schedule.”
This kind of scenario is becoming all too familiar this spring, according to oncologists who gathered at the annual meeting of the American Society of Clinical Oncology (ASCO). In interviews, these physicians said the limited supply of multiple cancer drugs – including the chemotherapies carboplatin and cisplatin – is having an unprecedented negative effect since their use is so widespread in cancer care.
“Every patient could get impacted. That’s why we need to address this sooner rather than later,” said oncologist Aditya Baria, MBBS, MPH, director of the Breast Cancer Research Program at Massachusetts General Hospital, Boston.
Shortages of cancer drugs are not unusual. Three-quarters of oncology pharmacists at 68 organizations surveyed from 2019 to 2020 said shortages prompted treatment delays, reduced doses, or alternative regimens. But the current shortages are having a much wider impact.
The National Comprehensive Cancer Network recently reported that 93% of 27 member institutions surveyed in late May are short on carboplatin, and 70% have reported a shortage of cisplatin. Plus, 20% of 19 centers said they weren’t able to continue carboplatin regimens for all patients.
The drugs are mainstays of multiple types of treatment for a long list of cancer types including lung, breast, gynecologic, and many others.
Several scenarios are possible when the drugs are in short supply, said Dr. Yardley, who noted that the shortage is more severe than any she’s seen in her medical career of more than 3 decades. Patients may need to be switched to regimens with more side effects, even when they’re in the middle of a treatment, she said. Or patients might have to go longer between treatments.
In some cases, Dr. Yardley said, the shortage is forcing patients to go without an important component of a larger combination therapy regimen. “The Keynote 522 neoadjuvant regimen for triple-negative breast cancer has carboplatin given with Taxol [paclitaxel] and Keytruda [pembrolizumab]. We are just deleting the carboplatin.”
She added that carboplatin is part of the following so-called TCHP regimen for HER2+ early-stage breast cancer: Taxotere (docetaxel), carboplatin, Herceptin (trastuzumab), and Perjeta (pertuzumab).
“You can delete [carboplatin] or consider substituting cyclophosphamide for carboplatin,” she said. But she cautioned the Keynote 522 and TCHP regimens haven’t been tested without carboplatin in curative-intent trials.
At Duke University in Durham, N.C., doses of carboplatin for many patients are being lowered by a third to the level that’s commonly used for older and frail patients, said oncologist Arif Kamal, MD, MBA, MHS, who works at the academic center and is the chief patient officer at the American Cancer Society.
“We don’t know if [the lower doses will negatively affect cancer patients’ outcomes]. What’s amazing is how many patients [are understanding about having to take smaller amounts of the chemotherapy],” he said.
Medical organizations are offering guidance. The Society of Gynecologic Oncology, for example, in late April recommended that oncologists increase intervals between chemotherapy treatments when appropriate, round down vial sizes to ensure “efficient use,” and eliminate or minimize use of cisplatin and carboplatin in certain platinum-resistant cancers.
In early June, ASCO published guidance regarding alternatives to cisplatin, carboplatin, and 5-fluorouracil, which is also in short supply, in gastrointestinal cancer. As the guidance notes, some alternatives are more untested or more toxic than ideal treatments.
In addition, ASCO has a webpage devoted to news and resources about shortages of cancer drugs. It offers drug availability updates, general guidance, and breast cancer guidance. ASCO also offers ethical guidance about handling drug shortages.
Patients in clinical trials and those who hope to join them are especially vulnerable to the drug shortage, oncologists interviewed for this story said. Cisplatin and carboplatin are the backbones of many clinical trials, Dr. Yardley said. “When you can’t supply a drug in one of the [trial] arms, that puts the whole trial on pause.”
Even clinics that have managed to find adequate supplies of the drugs are planning for when they run out.
“Our institution and other institutions are trying to come up with a rationing protocol, deciding which patients are going to get access, and which ones have reasonable alternatives,” radiation oncologist Corey Speers MD, PhD, of University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, said in an interview. “In some settings, there really isn’t an effective alternative. Or the alternatives are tens of thousands of dollars more expensive.”
Oncologists also noted that cisplatin and carboplatin aren’t the only cancer drugs in short supply.
“Methotrexate is critically low, and 5FU [fluorouracil] is critically low,” Dr. Yardley said, referring to drugs that each treat several types of cancer. According to the May NCNN survey, 67% of respondents reported low supplies of methotrexate, and 26% said they were low on 5FU.
“Viscous lidocaine is a component of many supportive care mouth rinses for the stomatitis caused by our drugs but is not available at all,” Dr. Yardley said.
She added that there are also low supplies of fludarabine, which is used to treat chronic lymphocytic lymphom; clofarabine, which is used to treat acute lymphoblastic leukemia; and rasburicase, which is used to treat high levels of uric acid in patients on chemotherapy.
Dr. Speers said his institution is facing a shortage of capecitabine, which is used to treat several types of cancer.
“Numerous trials have demonstrated the improved, safety, efficacy, and convenience of oral capecitabine. With the shortage we’re having to use infusional 5FU, which not only is less convenient but also ends up being more costly and requires infusion room space or continuous infusion pumps. This impacts our ability to treat cancer patients,” he said. “Our capacity is becoming more limited to accommodate these added patients, and we have to use infusional formulations of a drug that previously was readily available via an oral formulation. Patients and caregivers now have to come to the cancer center for appointments and infusions that previously weren’t needed as they could take an oral pill.”
Dr. Speers added that his institution is rationing methotrexate. “We are now prioritizing patients being treated with curative intent and adjusting protocols to use the lowest allowable doses to conserve supply,” he said.
The roots of the platinum chemotherapy drug shortage link back to the India-based Intas Pharmaceuticals company, a major manufacturer of cisplatin and carboplatin. According to Kellyann Zuzulo, spokeperson for Accord Healthcare, an Instas U.S. subsidiary, a facility inspection in December 2022 prompted a decision to temporarily stop making the drugs. The inspection identified multiple problems.
“Intas and Accord are working with the FDA on a plan to return to manufacturing,” Ms. Zuzulo said in an interview. “This will allow for continued production of products that will be prioritized based on medical necessity. A date has not yet been confirmed in which the facility will return to manufacturing for cisplatin, carboplatin or any other products.”
Ms. Zuzulo said the company is not a health care provider and cannot offer advice to patients about alternatives.
Other companies that make cisplatin and carboplatin have also reported shortages. In interviews, representatives for Fresenius Kabi and Pfizer said the companies have limited supplies because of increased demand – not because of manufacturing problems.
On June 12, the American Society of Health-System Pharmacists (ASHP) reported that carboplatin remains in short supply, with all five companies that sell the drug listed as having limited or back-ordered supplies. Cisplatin is also in short supply, the organization reported in a June 9 update, although some is available.
In a June 12 update on methotrexate, ASHP said manufacturing delays at Accord have caused a shortage, and other companies are running low due to increased demand.
As for the future, Congress and the Biden administration, according to a report by Bloomberg, are trying to figure out what to do regarding shortages of cheap generic drugs such as cisplatin and carboplatin. The FDA is exploring a partnership with a Chinese drugmaker to make cisplatin, NBC News reported.
However, fixes will be challenging, according to former FDA commissioner and Pfizer board member, Scott Gottlieb, MD.
“This generic business, particularly for these complex drugs, these complex formulations, is not a healthy business right now. Yet it’s a vital business from a public standpoint,” he told CBS News.
In an interview, Dr. Kamal said that there is even talk about boosting the prices of cheap generic drugs “to ensure that there’s enough incentive for multiple manufacturers to be involved.”
Dr. Kamal said he is crossing his fingers that cutting chemotherapy doses at his clinic doesn’t result in worse outcomes for his patients.
“Right now, I think dropping someone by 25% or 30% is okay. And for some patients, particularly in a curative setting, we try to keep them at as much as 100% as possible. But there’s just a lot of unknowns,” he said.
AT ASCO 2023
ACS officer provides ASCO highlights: Targeting hidden cancer, AI in oncology
And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.
Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.
Below are lightly edited excerpts from a conversation with Dr. Kamal:
Question: What are some of most groundbreaking studies released at ASCO?
Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.
For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).
Q: How do these findings add to current knowledge?
A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.
Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.
Q: What else struck you as especially important research?
A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.
This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.
Even in these smaller, early tumors, osimertinib makes a difference.
Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?
A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.
If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.
That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.
Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?
A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.
Q: How can AI be helpful to medical providers considering its limitations?
A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.
Q: Will AI threaten the careers of oncologists?
A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.
Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.
Dr. Kamal has no disclosures.
And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.
Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.
Below are lightly edited excerpts from a conversation with Dr. Kamal:
Question: What are some of most groundbreaking studies released at ASCO?
Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.
For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).
Q: How do these findings add to current knowledge?
A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.
Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.
Q: What else struck you as especially important research?
A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.
This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.
Even in these smaller, early tumors, osimertinib makes a difference.
Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?
A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.
If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.
That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.
Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?
A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.
Q: How can AI be helpful to medical providers considering its limitations?
A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.
Q: Will AI threaten the careers of oncologists?
A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.
Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.
Dr. Kamal has no disclosures.
And it didn’t just sparkle because of the sequined Taylor Swift fans clogging the nearby streets during the meeting.
Arif Kamal, MD, MBA, MHS, who is also an oncologist at Duke University, Durham, N.C., said he was impressed by a pair of landmark studies released at the meeting that show hidden cancer can be targeted with “really remarkable outcomes.” He also highlighted sessions that examined the role of artificial intelligence (AI) in oncology, during an interview.
Below are lightly edited excerpts from a conversation with Dr. Kamal:
Question: What are some of most groundbreaking studies released at ASCO?
Answer: One is an interim analysis of the NATALEE trial, which involved patients with early-stage hormone receptor-positive, HER2-negative (HR+/HER2–) breast tumors. This phase 3 randomized trial compared maintenance therapy with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor ribociclib (Kisqali) plus endocrine therapy with an aromatase inhibitor to endocrine therapy alone in patients with node-positive or node-negative and stage II or III HR+/HER– breast cancer.
For a long time, the standard care in these patients has been to use endocrine therapy alone. This is the first big trial to show that upstream usage of additional therapy in early stages is also beneficial for disease-free survival. The 3-year invasive disease-free survival rate was 90.4% in the rebociclib-endocrine therapy group vs. 87.1% for patients who received only endocrine therapy (P = .0014).
Q: How do these findings add to current knowledge?
A: Typically, we let people get metastatic disease before we use CDK4/6 inhibitors. These findings show that systemic treatment beyond endocrine therapy will be helpful in cases where you’ve got smaller disease that has not spread yet.
Even in patients with node-negative breast cancer, micrometastatic disease is clearly there, because the medication killed the negative lymph nodes.
Q: What else struck you as especially important research?
A: The NATALEE findings match what we saw in another study – the ADAURA trial, which looked at adjuvant osimertinib in non–small-cell lung cancer patients with EGFR-mutated, stage IB to IIIA disease – cancer that has not spread to the lymph nodes.
This is another example where you have a treatment being used in earlier-stage disease that’s showing really remarkable outcomes. The study found that 5-year overall survival was 88% in an osimertinib group vs. 78% in a placebo group (P < .001). This is a disease where, in stage IB, we wouldn’t even necessarily give these patients treatment at all, other than surgical resection of the tumor and maybe give them a little bit of chemotherapy.
Even in these smaller, early tumors, osimertinib makes a difference.
Q: As a whole, what are these studies telling us about cancer cells that can’t be easily detected?
A: To find a disease-free survival benefit with adding ribociclib in a stage II, stage III setting, particularly in node-negative disease, is remarkable because it says that the cells in hiding are bad actors, and they are going to cause trouble. The study shows that medications can find these cells and reverse that risk of bad outcomes.
If you think about the paradigm of cancer, that’s pretty remarkable because the ADAURA trial does the same thing: You do surgery for [early-stage] lung cancers that have not spread to the lymph nodes and you figure, “Well, I’ve got it all, right? The margins are real big, healthy, clean.” And yet, people still have recurrences, and you ask the same question: “Can any medicine find those few cells, the hundreds of cells that are still left somewhere in hiding?” And the answer is again, yes. It’s changing the paradigm of our understanding of minimal residual disease.
That’s why there’s so much interest in liquid biopsies. Let’s say that after treatment we don’t see any cancer radiologically, but there’s a signal from a liquid biopsy [detecting residual cancer]. These two trials demonstrate that there’s something we can do about it.
Q: There were quite a few studies about artificial intelligence released at ASCO. Where do we stand on that front?
A: We’re just at the beginning of people thinking about the use of generative AI for clinical decision support, clinical trial matching, and pathology review. But AI, at least for now, still has the issue of making up things that aren’t true. That’s not something patients are going to be okay with.
Q: How can AI be helpful to medical providers considering its limitations?
A: AI is going to be very good at the data-to-information transition. You’ll start seeing people use AI to start clinical notes for them and to match patients to the best clinical trials for them. But fundamentally, the clinician’s role will continue to be to check facts and offer wisdom.
Q: Will AI threaten the careers of oncologists?
A: The body of knowledge about oncology is growing exponentially, and no one can actually keep up. There’s so much data that’s out there that needs to be turned into usable information amid a shortage of oncologists. At the same time, the prevalence of cancer is going up, even though mortality is going down.
Synthesis of data is what oncologists are waiting for from AI. They’ll welcome it as opposed to being worried. That’s the sentiment I heard from my colleagues.
Dr. Kamal has no disclosures.
AT ASCO 2023
Breast cancer experts and other HCPs disagree on treatment strategies for early BC
The discrepancy suggests that many providers aren’t aware of the findings of recent landmark trials that formed the basis of the panel’s opinions, said study coauthor Denise A. Yardley, MD, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville, in an interview. The findings, based on responses to a treatment decision tool, were presented in a poster at the annual meeting of the American Society of Clinical Oncology.
Study methods and results
For the new study, researchers analyzed how 547 providers – and the panel – responded to 10 case scenarios in high-risk HER2– early breast cancer between June 2022 and January 2023.
Among the providers surveyed, 72% identified as physicians, including oncologists, hematologists/oncologists, surgery oncologists, radiation oncologists, and pathologists. One percent said they were nurse practitioners or physician assistants, 7% said they were pharmacists, 1% were nurses, and the specific roles of the remaining 19% were unknown, but included medical students, according to Dr. Yardley, who is a breast cancer oncologist.
The study authors developed the free decision tool – available via the medical education company Clinical Care Options – to help oncologists navigate new treatment options for high-risk HER2– early breast cancer. The Food and Drug Administration has recently approved drugs such as abemaciclib, olaparib, and pembrolizumab for the condition.
Health care providers enter details into the tool about their patients along with their intended treatment plans. The tool then shows them recommendations for treatment from a panel of five oncologists with expertise in oncology. The members of the panel based their perspectives on the findings of the KEYNOTE-522 (pembrolizumab), OlympiA (olaparib), and monarchE (abemaciclib) trials.
The oncologists with expertise in breast cancer, who provided recommendations in March 2022, generally agreed about the best treatments, Dr. Yardley said.
The other health care providers surveyed didn’t agree with the breast cancer experts about the best treatment 58.8% of the time.
For example, one scenario describes a HR+, HER2– patient with no deleterious BRCA mutation – or unknown status – who fits the monarchE high-risk criteria. All the breast cancer experts on the panel recommended abemaciclib and endocrine therapy. But 203 providers supported a variety of strategies: endocrine therapy alone (9%), chemotherapy followed by endocrine therapy (49%), and olaparib and endocrine therapy (2%). Only 37% opted for abemaciclib and endocrine therapy, and 4% were uncertain.
Another scenario describes a patient with triple-negative breast cancer with no residual disease after neoadjuvant chemotherapy. All the experts agreed on a strategy of no adjuvant therapy plus observation. Forty percent of 25 providers agreed with this approach, but 24% were uncertain, 12% chose pembrolizumab, and 24% chose capecitabine.
In many cases, providers chose more intensive treatment options than the experts did, Dr. Yardley said.
Overtreatment in cancer is often a reflex for oncologists, she said, although “we’re learning to deescalate these treatment algorithms where there is really no benefit [to extra treatment].”
“It’s a challenge for some of these oncologists who are busy and dealing with multiple solid tumor types to keep up with the nuances of a rapidly changing field,” Dr. Yardley noted.
Many community oncologists aren’t specialists in one type of cancer and must try to keep up with treatment recommendations regarding multiple types, she continued.
Decision tool’s value explained
According to the study, 32% of providers changed their treatment choices in clinical practice after they learned about the expert perspectives via the decision tool; 46% said the expert opinions confirmed that their choices were best practice.
The value of the tool is its ability to help providers make better decisions about patient care, Dr. Yardley said. “There seems to be a need for this kind of support.”
In an interview, University of Pittsburgh Medical Center oncologist Adam M. Brufsky, MD, PhD – who wasn’t involved with the study – said he was surprised by the amount of disagreement between the expert and provider perspectives on treatment. However, he noted that community oncologists – unlike the breast cancer experts – often don’t see just one type of cancer.
“You just have to know so much now as an oncologist,” Dr. Brufsky said. He recommended that colleagues take advantage of decision support tools, such as cancer treatment pathways.
The study was funded by AstraZeneca, Lilly, and Merck Sharp & Dohme. Dr. Yardley has no disclosures, and disclosure information from other authors was not available. Dr. Brufsky discloses consulting support from AstraZeneca, Lilly, and Merck and grants from AstraZeneca.
The discrepancy suggests that many providers aren’t aware of the findings of recent landmark trials that formed the basis of the panel’s opinions, said study coauthor Denise A. Yardley, MD, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville, in an interview. The findings, based on responses to a treatment decision tool, were presented in a poster at the annual meeting of the American Society of Clinical Oncology.
Study methods and results
For the new study, researchers analyzed how 547 providers – and the panel – responded to 10 case scenarios in high-risk HER2– early breast cancer between June 2022 and January 2023.
Among the providers surveyed, 72% identified as physicians, including oncologists, hematologists/oncologists, surgery oncologists, radiation oncologists, and pathologists. One percent said they were nurse practitioners or physician assistants, 7% said they were pharmacists, 1% were nurses, and the specific roles of the remaining 19% were unknown, but included medical students, according to Dr. Yardley, who is a breast cancer oncologist.
The study authors developed the free decision tool – available via the medical education company Clinical Care Options – to help oncologists navigate new treatment options for high-risk HER2– early breast cancer. The Food and Drug Administration has recently approved drugs such as abemaciclib, olaparib, and pembrolizumab for the condition.
Health care providers enter details into the tool about their patients along with their intended treatment plans. The tool then shows them recommendations for treatment from a panel of five oncologists with expertise in oncology. The members of the panel based their perspectives on the findings of the KEYNOTE-522 (pembrolizumab), OlympiA (olaparib), and monarchE (abemaciclib) trials.
The oncologists with expertise in breast cancer, who provided recommendations in March 2022, generally agreed about the best treatments, Dr. Yardley said.
The other health care providers surveyed didn’t agree with the breast cancer experts about the best treatment 58.8% of the time.
For example, one scenario describes a HR+, HER2– patient with no deleterious BRCA mutation – or unknown status – who fits the monarchE high-risk criteria. All the breast cancer experts on the panel recommended abemaciclib and endocrine therapy. But 203 providers supported a variety of strategies: endocrine therapy alone (9%), chemotherapy followed by endocrine therapy (49%), and olaparib and endocrine therapy (2%). Only 37% opted for abemaciclib and endocrine therapy, and 4% were uncertain.
Another scenario describes a patient with triple-negative breast cancer with no residual disease after neoadjuvant chemotherapy. All the experts agreed on a strategy of no adjuvant therapy plus observation. Forty percent of 25 providers agreed with this approach, but 24% were uncertain, 12% chose pembrolizumab, and 24% chose capecitabine.
In many cases, providers chose more intensive treatment options than the experts did, Dr. Yardley said.
Overtreatment in cancer is often a reflex for oncologists, she said, although “we’re learning to deescalate these treatment algorithms where there is really no benefit [to extra treatment].”
“It’s a challenge for some of these oncologists who are busy and dealing with multiple solid tumor types to keep up with the nuances of a rapidly changing field,” Dr. Yardley noted.
Many community oncologists aren’t specialists in one type of cancer and must try to keep up with treatment recommendations regarding multiple types, she continued.
Decision tool’s value explained
According to the study, 32% of providers changed their treatment choices in clinical practice after they learned about the expert perspectives via the decision tool; 46% said the expert opinions confirmed that their choices were best practice.
The value of the tool is its ability to help providers make better decisions about patient care, Dr. Yardley said. “There seems to be a need for this kind of support.”
In an interview, University of Pittsburgh Medical Center oncologist Adam M. Brufsky, MD, PhD – who wasn’t involved with the study – said he was surprised by the amount of disagreement between the expert and provider perspectives on treatment. However, he noted that community oncologists – unlike the breast cancer experts – often don’t see just one type of cancer.
“You just have to know so much now as an oncologist,” Dr. Brufsky said. He recommended that colleagues take advantage of decision support tools, such as cancer treatment pathways.
The study was funded by AstraZeneca, Lilly, and Merck Sharp & Dohme. Dr. Yardley has no disclosures, and disclosure information from other authors was not available. Dr. Brufsky discloses consulting support from AstraZeneca, Lilly, and Merck and grants from AstraZeneca.
The discrepancy suggests that many providers aren’t aware of the findings of recent landmark trials that formed the basis of the panel’s opinions, said study coauthor Denise A. Yardley, MD, of Tennessee Oncology and Sarah Cannon Research Institute in Nashville, in an interview. The findings, based on responses to a treatment decision tool, were presented in a poster at the annual meeting of the American Society of Clinical Oncology.
Study methods and results
For the new study, researchers analyzed how 547 providers – and the panel – responded to 10 case scenarios in high-risk HER2– early breast cancer between June 2022 and January 2023.
Among the providers surveyed, 72% identified as physicians, including oncologists, hematologists/oncologists, surgery oncologists, radiation oncologists, and pathologists. One percent said they were nurse practitioners or physician assistants, 7% said they were pharmacists, 1% were nurses, and the specific roles of the remaining 19% were unknown, but included medical students, according to Dr. Yardley, who is a breast cancer oncologist.
The study authors developed the free decision tool – available via the medical education company Clinical Care Options – to help oncologists navigate new treatment options for high-risk HER2– early breast cancer. The Food and Drug Administration has recently approved drugs such as abemaciclib, olaparib, and pembrolizumab for the condition.
Health care providers enter details into the tool about their patients along with their intended treatment plans. The tool then shows them recommendations for treatment from a panel of five oncologists with expertise in oncology. The members of the panel based their perspectives on the findings of the KEYNOTE-522 (pembrolizumab), OlympiA (olaparib), and monarchE (abemaciclib) trials.
The oncologists with expertise in breast cancer, who provided recommendations in March 2022, generally agreed about the best treatments, Dr. Yardley said.
The other health care providers surveyed didn’t agree with the breast cancer experts about the best treatment 58.8% of the time.
For example, one scenario describes a HR+, HER2– patient with no deleterious BRCA mutation – or unknown status – who fits the monarchE high-risk criteria. All the breast cancer experts on the panel recommended abemaciclib and endocrine therapy. But 203 providers supported a variety of strategies: endocrine therapy alone (9%), chemotherapy followed by endocrine therapy (49%), and olaparib and endocrine therapy (2%). Only 37% opted for abemaciclib and endocrine therapy, and 4% were uncertain.
Another scenario describes a patient with triple-negative breast cancer with no residual disease after neoadjuvant chemotherapy. All the experts agreed on a strategy of no adjuvant therapy plus observation. Forty percent of 25 providers agreed with this approach, but 24% were uncertain, 12% chose pembrolizumab, and 24% chose capecitabine.
In many cases, providers chose more intensive treatment options than the experts did, Dr. Yardley said.
Overtreatment in cancer is often a reflex for oncologists, she said, although “we’re learning to deescalate these treatment algorithms where there is really no benefit [to extra treatment].”
“It’s a challenge for some of these oncologists who are busy and dealing with multiple solid tumor types to keep up with the nuances of a rapidly changing field,” Dr. Yardley noted.
Many community oncologists aren’t specialists in one type of cancer and must try to keep up with treatment recommendations regarding multiple types, she continued.
Decision tool’s value explained
According to the study, 32% of providers changed their treatment choices in clinical practice after they learned about the expert perspectives via the decision tool; 46% said the expert opinions confirmed that their choices were best practice.
The value of the tool is its ability to help providers make better decisions about patient care, Dr. Yardley said. “There seems to be a need for this kind of support.”
In an interview, University of Pittsburgh Medical Center oncologist Adam M. Brufsky, MD, PhD – who wasn’t involved with the study – said he was surprised by the amount of disagreement between the expert and provider perspectives on treatment. However, he noted that community oncologists – unlike the breast cancer experts – often don’t see just one type of cancer.
“You just have to know so much now as an oncologist,” Dr. Brufsky said. He recommended that colleagues take advantage of decision support tools, such as cancer treatment pathways.
The study was funded by AstraZeneca, Lilly, and Merck Sharp & Dohme. Dr. Yardley has no disclosures, and disclosure information from other authors was not available. Dr. Brufsky discloses consulting support from AstraZeneca, Lilly, and Merck and grants from AstraZeneca.
AT ASCO 2023
What’s best for patients who are dying of anorexia?
SAN FRANCISCO – The patient at a Florida eating disorder clinic said she was eating plenty even though she acknowledged purging once a week. But her vitals told a different story: Her body mass index (BMI) was 12.2, down from 14.8 a couple of years before – a dangerously low value.
While the woman agreed that she needed to gain weight, she refused advice to pursue residential or inpatient treatment. This left her team with a big dilemma: Should they force her into care because she wouldn’t eat? Was that even possible under the law? Did she have the capacity to make decisions about her future? What other alternatives were there?
Determining the best course of action in cases like this is anything but simple, Dr. Cacodcar said. To make matters more complicated, .
“At least in my state of Florida, we know that it can be very, very hard to get patients expert care,” said Dr. Cacodcar. And, she said, it can be even tougher for certain types of patients, such as those that are LGBTQ and those who have severe illness but don’t meet the criteria.
As Dr. Cacodcar noted, the APA released new practice guidelines regarding eating disorders earlier this year, marking their first update since 2006. The guidelines highlight research that suggests nearly 1% – 0.8% – of the U.S. population will develop AN over their lifetimes. Recent studies also suggest that eating disorder numbers rose during the pandemic, with one analysis finding that patients under inpatient care doubled in 2020.
“Mortality rates are high for anorexia nervosa, up to 10 times higher than matched controls,” Dr. Cacodcar said. “It has the highest mortality rate of the psychiatric diseases with the exception of opioid use disorder.”
As for outcomes, she pointed to a 2019 study that surveyed 387 parents who had children with eating disorders, mostly AN. Only 20% made a full recovery. “The farther you get out from the onset of anorexia, the less likely you are to achieve recovery,” Dr. Cacodcar said. “A lot of the control behaviors become very automatic.”
Determining capacity
In some cases of AN, psychiatrists must determine whether they have the capacity to make decisions about treatment, said Gabriel Jerkins, MD, a chief resident of psychiatry at the University of Florida. At issue is “the ability of the individual to comprehend the information being disclosed in regard to their condition, as well as the nature and potential risks and benefits of the proposed treatment alternatives. They include of course, no treatment at all.”
“We know psychiatric conditions can limit one’s ability to appreciate consequence,” he said.
One option is to seek to institutionalize patients with severe AN because they are a danger to themselves. Clinicians opted to not do this in the case of the patient profiled by Dr. Cacodcar, the one with the BMI of 12.2 who didn’t want inpatient or residential care. (A 5-foot-8 person with a BMI of 12.2 would weigh 80 pounds.)
“The main reason we did not hospitalize her is because an appropriate level of care was not going to be readily available,” Dr. Cacodcar said, and her treatment would have been substandard.
Fortunately, the woman did return after a couple of months and accept residential care. No facility in Florida was willing to accept her because of her low BMI, but she did find one in North Carolina, where she stayed for 2 months. She’s doing well, and her BMI is now 21, Dr. Cacodcar said.
The patient’s story shows that involuntary hospitalization “is not necessarily the best course of action,” Dr. Cacodcar said. “It wasn’t necessarily going to be in the patient’s best interest.”
In another case, a 22-year-old woman had severe AN. She had been a gymnast and dancer, Dr. Jerkins said, “and I include that here only because of how commonly we see that kind of demographic information in patients with anorexia nervosa.”
Her BMI was 17.5, and clinicians discussed feeding her through a feeding tube. She still had “no insight that her symptoms were related to an underlying eating disorder,” Dr. Jerkins said, raising questions about her capacity. “Is it sufficient that the patient understand that she’s underweight?”
Ultimately, he said, she received a feeding tube at a time when her BMI had dropped to 16.3. She suffered from an infection but ultimately she improved and has stabilized at a BMI of around 19, he said.
“I do wonder if allowing her to have some control of how to pursue treatment in this case was therapeutic in a way,” he said, especially since matters of control are deeply ingrained in AN.
A former physical trainer, the patient had a BMI of 17.6. The University of Florida’s eating disorder clinic sent her to an out-of-state residential program, but she was discharged when her blood glucose dipped dangerously low as she compulsively exercised. Her BMI dipped to 16.2.
Dr. Schmidt had the patient involuntarily committed upon her return, but she went home after 12 days with no change in her weight. Ultimately, the patient was referred to an eating disorder center in Colorado for medical stabilization where she was given a feeding tube. But her medical situation was so dire that she was discharged to her home, where she went on hospice and died.
“I’m not arguing for or against the term ‘terminal anorexia.’ But this case does make me think about it,” said Dr. Schmidt. She was referring to a controversial term used by some clinicians to refer to patients who face inevitable death from AN. “Unfortunately,” wrote the authors of a recent report proposing a clinical definition, “these patients and their carers often receive minimal support from eating disorders health professionals who are conflicted about terminal care, and who are hampered and limited by the paucity of literature on end-of-life care for those with anorexia nervosa.”
SAN FRANCISCO – The patient at a Florida eating disorder clinic said she was eating plenty even though she acknowledged purging once a week. But her vitals told a different story: Her body mass index (BMI) was 12.2, down from 14.8 a couple of years before – a dangerously low value.
While the woman agreed that she needed to gain weight, she refused advice to pursue residential or inpatient treatment. This left her team with a big dilemma: Should they force her into care because she wouldn’t eat? Was that even possible under the law? Did she have the capacity to make decisions about her future? What other alternatives were there?
Determining the best course of action in cases like this is anything but simple, Dr. Cacodcar said. To make matters more complicated, .
“At least in my state of Florida, we know that it can be very, very hard to get patients expert care,” said Dr. Cacodcar. And, she said, it can be even tougher for certain types of patients, such as those that are LGBTQ and those who have severe illness but don’t meet the criteria.
As Dr. Cacodcar noted, the APA released new practice guidelines regarding eating disorders earlier this year, marking their first update since 2006. The guidelines highlight research that suggests nearly 1% – 0.8% – of the U.S. population will develop AN over their lifetimes. Recent studies also suggest that eating disorder numbers rose during the pandemic, with one analysis finding that patients under inpatient care doubled in 2020.
“Mortality rates are high for anorexia nervosa, up to 10 times higher than matched controls,” Dr. Cacodcar said. “It has the highest mortality rate of the psychiatric diseases with the exception of opioid use disorder.”
As for outcomes, she pointed to a 2019 study that surveyed 387 parents who had children with eating disorders, mostly AN. Only 20% made a full recovery. “The farther you get out from the onset of anorexia, the less likely you are to achieve recovery,” Dr. Cacodcar said. “A lot of the control behaviors become very automatic.”
Determining capacity
In some cases of AN, psychiatrists must determine whether they have the capacity to make decisions about treatment, said Gabriel Jerkins, MD, a chief resident of psychiatry at the University of Florida. At issue is “the ability of the individual to comprehend the information being disclosed in regard to their condition, as well as the nature and potential risks and benefits of the proposed treatment alternatives. They include of course, no treatment at all.”
“We know psychiatric conditions can limit one’s ability to appreciate consequence,” he said.
One option is to seek to institutionalize patients with severe AN because they are a danger to themselves. Clinicians opted to not do this in the case of the patient profiled by Dr. Cacodcar, the one with the BMI of 12.2 who didn’t want inpatient or residential care. (A 5-foot-8 person with a BMI of 12.2 would weigh 80 pounds.)
“The main reason we did not hospitalize her is because an appropriate level of care was not going to be readily available,” Dr. Cacodcar said, and her treatment would have been substandard.
Fortunately, the woman did return after a couple of months and accept residential care. No facility in Florida was willing to accept her because of her low BMI, but she did find one in North Carolina, where she stayed for 2 months. She’s doing well, and her BMI is now 21, Dr. Cacodcar said.
The patient’s story shows that involuntary hospitalization “is not necessarily the best course of action,” Dr. Cacodcar said. “It wasn’t necessarily going to be in the patient’s best interest.”
In another case, a 22-year-old woman had severe AN. She had been a gymnast and dancer, Dr. Jerkins said, “and I include that here only because of how commonly we see that kind of demographic information in patients with anorexia nervosa.”
Her BMI was 17.5, and clinicians discussed feeding her through a feeding tube. She still had “no insight that her symptoms were related to an underlying eating disorder,” Dr. Jerkins said, raising questions about her capacity. “Is it sufficient that the patient understand that she’s underweight?”
Ultimately, he said, she received a feeding tube at a time when her BMI had dropped to 16.3. She suffered from an infection but ultimately she improved and has stabilized at a BMI of around 19, he said.
“I do wonder if allowing her to have some control of how to pursue treatment in this case was therapeutic in a way,” he said, especially since matters of control are deeply ingrained in AN.
A former physical trainer, the patient had a BMI of 17.6. The University of Florida’s eating disorder clinic sent her to an out-of-state residential program, but she was discharged when her blood glucose dipped dangerously low as she compulsively exercised. Her BMI dipped to 16.2.
Dr. Schmidt had the patient involuntarily committed upon her return, but she went home after 12 days with no change in her weight. Ultimately, the patient was referred to an eating disorder center in Colorado for medical stabilization where she was given a feeding tube. But her medical situation was so dire that she was discharged to her home, where she went on hospice and died.
“I’m not arguing for or against the term ‘terminal anorexia.’ But this case does make me think about it,” said Dr. Schmidt. She was referring to a controversial term used by some clinicians to refer to patients who face inevitable death from AN. “Unfortunately,” wrote the authors of a recent report proposing a clinical definition, “these patients and their carers often receive minimal support from eating disorders health professionals who are conflicted about terminal care, and who are hampered and limited by the paucity of literature on end-of-life care for those with anorexia nervosa.”
SAN FRANCISCO – The patient at a Florida eating disorder clinic said she was eating plenty even though she acknowledged purging once a week. But her vitals told a different story: Her body mass index (BMI) was 12.2, down from 14.8 a couple of years before – a dangerously low value.
While the woman agreed that she needed to gain weight, she refused advice to pursue residential or inpatient treatment. This left her team with a big dilemma: Should they force her into care because she wouldn’t eat? Was that even possible under the law? Did she have the capacity to make decisions about her future? What other alternatives were there?
Determining the best course of action in cases like this is anything but simple, Dr. Cacodcar said. To make matters more complicated, .
“At least in my state of Florida, we know that it can be very, very hard to get patients expert care,” said Dr. Cacodcar. And, she said, it can be even tougher for certain types of patients, such as those that are LGBTQ and those who have severe illness but don’t meet the criteria.
As Dr. Cacodcar noted, the APA released new practice guidelines regarding eating disorders earlier this year, marking their first update since 2006. The guidelines highlight research that suggests nearly 1% – 0.8% – of the U.S. population will develop AN over their lifetimes. Recent studies also suggest that eating disorder numbers rose during the pandemic, with one analysis finding that patients under inpatient care doubled in 2020.
“Mortality rates are high for anorexia nervosa, up to 10 times higher than matched controls,” Dr. Cacodcar said. “It has the highest mortality rate of the psychiatric diseases with the exception of opioid use disorder.”
As for outcomes, she pointed to a 2019 study that surveyed 387 parents who had children with eating disorders, mostly AN. Only 20% made a full recovery. “The farther you get out from the onset of anorexia, the less likely you are to achieve recovery,” Dr. Cacodcar said. “A lot of the control behaviors become very automatic.”
Determining capacity
In some cases of AN, psychiatrists must determine whether they have the capacity to make decisions about treatment, said Gabriel Jerkins, MD, a chief resident of psychiatry at the University of Florida. At issue is “the ability of the individual to comprehend the information being disclosed in regard to their condition, as well as the nature and potential risks and benefits of the proposed treatment alternatives. They include of course, no treatment at all.”
“We know psychiatric conditions can limit one’s ability to appreciate consequence,” he said.
One option is to seek to institutionalize patients with severe AN because they are a danger to themselves. Clinicians opted to not do this in the case of the patient profiled by Dr. Cacodcar, the one with the BMI of 12.2 who didn’t want inpatient or residential care. (A 5-foot-8 person with a BMI of 12.2 would weigh 80 pounds.)
“The main reason we did not hospitalize her is because an appropriate level of care was not going to be readily available,” Dr. Cacodcar said, and her treatment would have been substandard.
Fortunately, the woman did return after a couple of months and accept residential care. No facility in Florida was willing to accept her because of her low BMI, but she did find one in North Carolina, where she stayed for 2 months. She’s doing well, and her BMI is now 21, Dr. Cacodcar said.
The patient’s story shows that involuntary hospitalization “is not necessarily the best course of action,” Dr. Cacodcar said. “It wasn’t necessarily going to be in the patient’s best interest.”
In another case, a 22-year-old woman had severe AN. She had been a gymnast and dancer, Dr. Jerkins said, “and I include that here only because of how commonly we see that kind of demographic information in patients with anorexia nervosa.”
Her BMI was 17.5, and clinicians discussed feeding her through a feeding tube. She still had “no insight that her symptoms were related to an underlying eating disorder,” Dr. Jerkins said, raising questions about her capacity. “Is it sufficient that the patient understand that she’s underweight?”
Ultimately, he said, she received a feeding tube at a time when her BMI had dropped to 16.3. She suffered from an infection but ultimately she improved and has stabilized at a BMI of around 19, he said.
“I do wonder if allowing her to have some control of how to pursue treatment in this case was therapeutic in a way,” he said, especially since matters of control are deeply ingrained in AN.
A former physical trainer, the patient had a BMI of 17.6. The University of Florida’s eating disorder clinic sent her to an out-of-state residential program, but she was discharged when her blood glucose dipped dangerously low as she compulsively exercised. Her BMI dipped to 16.2.
Dr. Schmidt had the patient involuntarily committed upon her return, but she went home after 12 days with no change in her weight. Ultimately, the patient was referred to an eating disorder center in Colorado for medical stabilization where she was given a feeding tube. But her medical situation was so dire that she was discharged to her home, where she went on hospice and died.
“I’m not arguing for or against the term ‘terminal anorexia.’ But this case does make me think about it,” said Dr. Schmidt. She was referring to a controversial term used by some clinicians to refer to patients who face inevitable death from AN. “Unfortunately,” wrote the authors of a recent report proposing a clinical definition, “these patients and their carers often receive minimal support from eating disorders health professionals who are conflicted about terminal care, and who are hampered and limited by the paucity of literature on end-of-life care for those with anorexia nervosa.”
AT APA 2023
Treatment-resistant depression? Don’t forget about MAOIs
SAN FRANCISCO – University of California, San Diego, psychiatrist Stephen M. Stahl, MD, PhD, has heard the scary stories about monoamine oxidase inhibitors (MAOIs): Patients supposedly need to be on restrictive diets free of culinary joys like cheese, beer, and wine; they can’t take cold medicines; and they can just forget about anesthesia for dental work or surgery.
Wrong, wrong, and wrong, Dr. Stahl told an audience at the annual meeting of the American Psychiatric Association. While the venerable antidepressants can transform the lives of patients with treatment-resistant depression, he said, .
“These are good options,” he said. “Everybody who prescribes these today, without exception, has seen patients respond after nothing else has – including ECT (electroconvulsive therapy).”
Still, MAOIs, which were first developed in the 1950s, remain little-used in the United States. While an average of six selective serotonin reuptake inhibitors (SSRIs) are prescribed every second in the United States each day, Dr. Stahl said, “there are only a few hundred MAOI prescribers for a few thousand patients.”
The main barrier to the use of the drugs is unfamiliarity, he said. Despite their low profile, they’re appropriate to use after failures of monotherapy with SSRIs/serotonin and norepinephrine reuptake inhibitors (SNRIs) and augmentation with atypical antipsychotics. And they can be used in conjunction with ketamine/esketamine and ECT, which are other options for treatment-resistant depression, he said.
As for the myths about MAOIs, Dr. Stahl said the drugs can indeed interact with tyramine, which is found in foods like cheese, beer, and wine. The interaction can lead to potentially fatal hypertensive crises, Dr. Stahl said, noting that patients should avoid aged cheeses, tap and unpasteurized beer, soy products, and certain other foods. (Patients taking 6 mg transdermal or low-dose oral selegiline can ignore these restrictions.)
But canned beer, certain wines, yogurt, fresh American cheese, mozzarella/pizza chain cheese, cream cheese, and fresh or processed meat/poultry/fish are fine, he said. “Selectively, you can have a pretty high tyramine diet,” he added, although it’s a good idea for patients to have a blood pressure monitor at home.
As for cold medicines, sympathomimetic decongestants and stimulants should be used cautiously with blood pressure monitoring or not at all, he said, but those with codeine or expectorants are OK. Dextromethorphan, a weak serotonin reuptake inhibitor in some cough medicine, should be avoided. However, antihistamines other than chlorpheniramine/brompheniramine are OK to use, he added, and they may be the ideal choice for cold relief.
As for anesthesia, he cautioned that local anesthetics with epinephrine and general anesthesia can disrupt blood pressure. Choose a local anesthetic that does not contain vasoconstrictors, he said, and if surgery with general anesthesia is needed, “you can wash [the MAOI] out if you want” ahead of time.
Benzodiazepines, mivacurium, rapacuronium, morphine, or codeine can be used cautiously, he said, in urgent or elective surgery in a patient on an MAOI.
As for other myths, he said tricyclic antidepressants and related drugs aren’t as troublesome as psychiatrists may assume. Clomipramine and imipramine should be avoided. But other tricyclic antidepressants can be used with caution.
As for painkillers, he said it’s not true that they must be avoided, although MAIOs shouldn’t be taken with meperidine, fentanyl, methadone, tramadol, or tapentadol. Other painkillers, including over-the-counter products like aspirin, NSAIDs, and acetaminophen, should be used with caution, he said. And expert guidance is advised for use of hydromorphone, morphine, oxycodone, or oxymorphone.
In the big picture, he noted, myths are so prevalent “that you have more calls from patients – and other doctors, dentists, and anesthesiologists – about MAO inhibitors then you will ever have about any other drug there.”
Columbia University, New York, psychiatrist Jonathan W. Stewart, MD, also spoke at the presentation on MAIOs at the APA conference. He recommended that colleagues consider the drugs if two or more antidepressants that work in different ways fail to provide relief after 4 weeks at a sufficient dose. Start low with one pill a day, he recommended, and seek full remission – no depressed mood – instead of simply “better.”
Ultimately, he said, “we do patients a disservice” if MAOIs aren’t considered in the appropriate patients.
Dr. Stahl discloses grant/research support (Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn, Daiichi Sankyo-Brazil Eisai, Eli Lilly, Harmony, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent), consultant/advisor support (Acadia, Alkermes, Allergan, AbbVie, Axsome, Clearview, Done, Eisai Pharmaceuticals, Gedeon Richter, Intra-Cellular Therapies, Karuna, Levo, Lundbeck, Neurocrine, Neurawell, Otsuka, Relmada, Sage, Sunovion, Supernus, Taliaz, Teva, Tris Pharma, and VistaGen), speakers bureau payments (Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva), and options in Genomind, Lipidio, Neurawell and Delix. Dr. Stewart discloses unspecified relationships with Eli Lilly, Pfizer, Merck, Boeringer- Ingleheim, Bristol-Myers, Sinolfi-Aventis, Amilyn, Novartis, Organon, GlaxoSmithKlein, Shire, and Somerset.
SAN FRANCISCO – University of California, San Diego, psychiatrist Stephen M. Stahl, MD, PhD, has heard the scary stories about monoamine oxidase inhibitors (MAOIs): Patients supposedly need to be on restrictive diets free of culinary joys like cheese, beer, and wine; they can’t take cold medicines; and they can just forget about anesthesia for dental work or surgery.
Wrong, wrong, and wrong, Dr. Stahl told an audience at the annual meeting of the American Psychiatric Association. While the venerable antidepressants can transform the lives of patients with treatment-resistant depression, he said, .
“These are good options,” he said. “Everybody who prescribes these today, without exception, has seen patients respond after nothing else has – including ECT (electroconvulsive therapy).”
Still, MAOIs, which were first developed in the 1950s, remain little-used in the United States. While an average of six selective serotonin reuptake inhibitors (SSRIs) are prescribed every second in the United States each day, Dr. Stahl said, “there are only a few hundred MAOI prescribers for a few thousand patients.”
The main barrier to the use of the drugs is unfamiliarity, he said. Despite their low profile, they’re appropriate to use after failures of monotherapy with SSRIs/serotonin and norepinephrine reuptake inhibitors (SNRIs) and augmentation with atypical antipsychotics. And they can be used in conjunction with ketamine/esketamine and ECT, which are other options for treatment-resistant depression, he said.
As for the myths about MAOIs, Dr. Stahl said the drugs can indeed interact with tyramine, which is found in foods like cheese, beer, and wine. The interaction can lead to potentially fatal hypertensive crises, Dr. Stahl said, noting that patients should avoid aged cheeses, tap and unpasteurized beer, soy products, and certain other foods. (Patients taking 6 mg transdermal or low-dose oral selegiline can ignore these restrictions.)
But canned beer, certain wines, yogurt, fresh American cheese, mozzarella/pizza chain cheese, cream cheese, and fresh or processed meat/poultry/fish are fine, he said. “Selectively, you can have a pretty high tyramine diet,” he added, although it’s a good idea for patients to have a blood pressure monitor at home.
As for cold medicines, sympathomimetic decongestants and stimulants should be used cautiously with blood pressure monitoring or not at all, he said, but those with codeine or expectorants are OK. Dextromethorphan, a weak serotonin reuptake inhibitor in some cough medicine, should be avoided. However, antihistamines other than chlorpheniramine/brompheniramine are OK to use, he added, and they may be the ideal choice for cold relief.
As for anesthesia, he cautioned that local anesthetics with epinephrine and general anesthesia can disrupt blood pressure. Choose a local anesthetic that does not contain vasoconstrictors, he said, and if surgery with general anesthesia is needed, “you can wash [the MAOI] out if you want” ahead of time.
Benzodiazepines, mivacurium, rapacuronium, morphine, or codeine can be used cautiously, he said, in urgent or elective surgery in a patient on an MAOI.
As for other myths, he said tricyclic antidepressants and related drugs aren’t as troublesome as psychiatrists may assume. Clomipramine and imipramine should be avoided. But other tricyclic antidepressants can be used with caution.
As for painkillers, he said it’s not true that they must be avoided, although MAIOs shouldn’t be taken with meperidine, fentanyl, methadone, tramadol, or tapentadol. Other painkillers, including over-the-counter products like aspirin, NSAIDs, and acetaminophen, should be used with caution, he said. And expert guidance is advised for use of hydromorphone, morphine, oxycodone, or oxymorphone.
In the big picture, he noted, myths are so prevalent “that you have more calls from patients – and other doctors, dentists, and anesthesiologists – about MAO inhibitors then you will ever have about any other drug there.”
Columbia University, New York, psychiatrist Jonathan W. Stewart, MD, also spoke at the presentation on MAIOs at the APA conference. He recommended that colleagues consider the drugs if two or more antidepressants that work in different ways fail to provide relief after 4 weeks at a sufficient dose. Start low with one pill a day, he recommended, and seek full remission – no depressed mood – instead of simply “better.”
Ultimately, he said, “we do patients a disservice” if MAOIs aren’t considered in the appropriate patients.
Dr. Stahl discloses grant/research support (Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn, Daiichi Sankyo-Brazil Eisai, Eli Lilly, Harmony, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent), consultant/advisor support (Acadia, Alkermes, Allergan, AbbVie, Axsome, Clearview, Done, Eisai Pharmaceuticals, Gedeon Richter, Intra-Cellular Therapies, Karuna, Levo, Lundbeck, Neurocrine, Neurawell, Otsuka, Relmada, Sage, Sunovion, Supernus, Taliaz, Teva, Tris Pharma, and VistaGen), speakers bureau payments (Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva), and options in Genomind, Lipidio, Neurawell and Delix. Dr. Stewart discloses unspecified relationships with Eli Lilly, Pfizer, Merck, Boeringer- Ingleheim, Bristol-Myers, Sinolfi-Aventis, Amilyn, Novartis, Organon, GlaxoSmithKlein, Shire, and Somerset.
SAN FRANCISCO – University of California, San Diego, psychiatrist Stephen M. Stahl, MD, PhD, has heard the scary stories about monoamine oxidase inhibitors (MAOIs): Patients supposedly need to be on restrictive diets free of culinary joys like cheese, beer, and wine; they can’t take cold medicines; and they can just forget about anesthesia for dental work or surgery.
Wrong, wrong, and wrong, Dr. Stahl told an audience at the annual meeting of the American Psychiatric Association. While the venerable antidepressants can transform the lives of patients with treatment-resistant depression, he said, .
“These are good options,” he said. “Everybody who prescribes these today, without exception, has seen patients respond after nothing else has – including ECT (electroconvulsive therapy).”
Still, MAOIs, which were first developed in the 1950s, remain little-used in the United States. While an average of six selective serotonin reuptake inhibitors (SSRIs) are prescribed every second in the United States each day, Dr. Stahl said, “there are only a few hundred MAOI prescribers for a few thousand patients.”
The main barrier to the use of the drugs is unfamiliarity, he said. Despite their low profile, they’re appropriate to use after failures of monotherapy with SSRIs/serotonin and norepinephrine reuptake inhibitors (SNRIs) and augmentation with atypical antipsychotics. And they can be used in conjunction with ketamine/esketamine and ECT, which are other options for treatment-resistant depression, he said.
As for the myths about MAOIs, Dr. Stahl said the drugs can indeed interact with tyramine, which is found in foods like cheese, beer, and wine. The interaction can lead to potentially fatal hypertensive crises, Dr. Stahl said, noting that patients should avoid aged cheeses, tap and unpasteurized beer, soy products, and certain other foods. (Patients taking 6 mg transdermal or low-dose oral selegiline can ignore these restrictions.)
But canned beer, certain wines, yogurt, fresh American cheese, mozzarella/pizza chain cheese, cream cheese, and fresh or processed meat/poultry/fish are fine, he said. “Selectively, you can have a pretty high tyramine diet,” he added, although it’s a good idea for patients to have a blood pressure monitor at home.
As for cold medicines, sympathomimetic decongestants and stimulants should be used cautiously with blood pressure monitoring or not at all, he said, but those with codeine or expectorants are OK. Dextromethorphan, a weak serotonin reuptake inhibitor in some cough medicine, should be avoided. However, antihistamines other than chlorpheniramine/brompheniramine are OK to use, he added, and they may be the ideal choice for cold relief.
As for anesthesia, he cautioned that local anesthetics with epinephrine and general anesthesia can disrupt blood pressure. Choose a local anesthetic that does not contain vasoconstrictors, he said, and if surgery with general anesthesia is needed, “you can wash [the MAOI] out if you want” ahead of time.
Benzodiazepines, mivacurium, rapacuronium, morphine, or codeine can be used cautiously, he said, in urgent or elective surgery in a patient on an MAOI.
As for other myths, he said tricyclic antidepressants and related drugs aren’t as troublesome as psychiatrists may assume. Clomipramine and imipramine should be avoided. But other tricyclic antidepressants can be used with caution.
As for painkillers, he said it’s not true that they must be avoided, although MAIOs shouldn’t be taken with meperidine, fentanyl, methadone, tramadol, or tapentadol. Other painkillers, including over-the-counter products like aspirin, NSAIDs, and acetaminophen, should be used with caution, he said. And expert guidance is advised for use of hydromorphone, morphine, oxycodone, or oxymorphone.
In the big picture, he noted, myths are so prevalent “that you have more calls from patients – and other doctors, dentists, and anesthesiologists – about MAO inhibitors then you will ever have about any other drug there.”
Columbia University, New York, psychiatrist Jonathan W. Stewart, MD, also spoke at the presentation on MAIOs at the APA conference. He recommended that colleagues consider the drugs if two or more antidepressants that work in different ways fail to provide relief after 4 weeks at a sufficient dose. Start low with one pill a day, he recommended, and seek full remission – no depressed mood – instead of simply “better.”
Ultimately, he said, “we do patients a disservice” if MAOIs aren’t considered in the appropriate patients.
Dr. Stahl discloses grant/research support (Acadia, Allergan/AbbVie, Avanir, Boehringer Ingelheim Braeburn, Daiichi Sankyo-Brazil Eisai, Eli Lilly, Harmony, Indivior, Intra-Cellular Therapies, Ironshore, Neurocrine, Otsuka, Pear Therapeutics, Sage, Shire Sunovion, Supernus, and Torrent), consultant/advisor support (Acadia, Alkermes, Allergan, AbbVie, Axsome, Clearview, Done, Eisai Pharmaceuticals, Gedeon Richter, Intra-Cellular Therapies, Karuna, Levo, Lundbeck, Neurocrine, Neurawell, Otsuka, Relmada, Sage, Sunovion, Supernus, Taliaz, Teva, Tris Pharma, and VistaGen), speakers bureau payments (Acadia, Lundbeck, Neurocrine, Otsuka, Servier, Sunovion, and Teva), and options in Genomind, Lipidio, Neurawell and Delix. Dr. Stewart discloses unspecified relationships with Eli Lilly, Pfizer, Merck, Boeringer- Ingleheim, Bristol-Myers, Sinolfi-Aventis, Amilyn, Novartis, Organon, GlaxoSmithKlein, Shire, and Somerset.
AT APA 2023
Psychiatrists: Don’t fear clozapine in treatment-resistant schizophrenia
SAN FRANCISCO – A trio of psychiatrists urged colleagues at the annual meeting of the American Psychiatric Association to embrace the venerable antipsychotic clozapine in patients with treatment-resistant schizophrenia. They cautioned that clinicians may overestimate the true risk of the adverse effect of neutropenia in minority populations.
“Although clozapine is known to be a life-improving and even potentially lifesaving treatment, it remains underutilized in the U.S.,” said Claire C. Holderness, MD, a psychiatrist at Columbia University Irving Medical Center, New York. “It’s been estimated that between 35% and 40% of all patients with schizophrenia should be considered for a clozapine trial. However, only 4%-5% of patients with schizophrenia in the U.S. have ever received clozapine. This is in sharp contrast to other industrialized countries where approximately 20% or more of patients with schizophrenia are treated with clozapine.”
According to Dr. Holderness, research has shown that clozapine is even less likely to be prescribed to racial and ethnic minorities. A 2022 systematic review, for example, found that Black patients in the United States had between one-third and two-thirds the odds of being treated with the drug, compared with White patients after adjustment for potential confounders such as demographics. Hispanic/Latino patients were also less likely than Whites to be prescribed the drug.
As Dr. Holderness put it, the drug “been shown to be more effective in treatment-resistant schizophrenia than any other antipsychotic medication. Clozapine is also the most cost-effective treatment for treatment-resistant schizophrenia.” So why does this disparity exist despite clozapine’s benefits?
A 2018 systematic review of barriers to the drug’s usage identified several factors: “mandatory blood testing, fear of serious side-effects and lack of adherence by the patients, difficulty in identifying suitable patients, service fragmentation, and inadequate training in or exposure to using clozapine.” A 2016 British study, meanwhile, looked at the reasons that 45% of 316 patients stopped clozapine before 2 years. More than half of these patients stopped because of adverse effects.
Risk of neutropenia
At the APA presentation, psychiatrist Laura Clarke, MD, also of Columbia University Irving Medical Center, noted that there’s concern about one adverse effect in particular: neutropenia, or an abnormally low white blood cell count. Clozapine, she said, has a boxed warning about severe neutropenia that can lead to death.
However, she cautioned that white blood cell counts can be misleading. Some people in non-White ethnic groups have a condition known as benign ethnic neutropenia: their white blood cell counts are abnormal by the standards of people of European heritage, but they’re otherwise healthy. “These individuals do not show an increased risk of infections, and their response to infection is similar to those without them,” she said.
As many as 25%-50% of people of African ancestry may have benign ethnic neutropenia, making their blood levels appear abnormally low. Others with higher levels of the condition include certain Middle Eastern ethnicities and other ethnic groups with darker skin.
In these patents, “clinicians may avoid prescribing clozapine out of the mistaken concern that it can worsen neutropenia,” Dr. Clarke said. In fact, benign ethnic neutropenia “does not increase the risk of clozapine-induced severe neutropenia.”
Dr. Clarke highlighted drug use guidelines from the Clozapine Risk Evaluation and Mitigation Strategy, a Food and Drug Administration–mandated safety program designed to prevent severe neutropenia in patients taking clozapine. The guidelines note that the recommended absolute neutrophil count monitoring algorithm differs when patients are diagnosed with benign ethnic neutropenia.
T. Scott Stroup, MD, MPH, a psychiatrist at Columbia University, New York, urged his colleagues to consider clozapine early on in treatment-resistant schizophrenia. “Don’t go through three, four, or five antipsychotics. Even after trying two, I’d encourage people to [try clozapine].”
However, he acknowledged that “not everyone believes that. Many of my colleagues think that, before you try clozapine, you should have a trial of long-acting injectable medications to rule out pseudo–treatment resistance. I don’t totally agree with that, but I’ve more or less lost that battle,” he added.
In the big picture, Dr. Stroup said, clozapine “is good when other things aren’t working efficacy wise.”
Dr. Holderness and Dr. Clarke have no disclosures. Dr. Stroup discloses grants from the National Institutes of Health and royalties from APA Publishing and UpToDate.
SAN FRANCISCO – A trio of psychiatrists urged colleagues at the annual meeting of the American Psychiatric Association to embrace the venerable antipsychotic clozapine in patients with treatment-resistant schizophrenia. They cautioned that clinicians may overestimate the true risk of the adverse effect of neutropenia in minority populations.
“Although clozapine is known to be a life-improving and even potentially lifesaving treatment, it remains underutilized in the U.S.,” said Claire C. Holderness, MD, a psychiatrist at Columbia University Irving Medical Center, New York. “It’s been estimated that between 35% and 40% of all patients with schizophrenia should be considered for a clozapine trial. However, only 4%-5% of patients with schizophrenia in the U.S. have ever received clozapine. This is in sharp contrast to other industrialized countries where approximately 20% or more of patients with schizophrenia are treated with clozapine.”
According to Dr. Holderness, research has shown that clozapine is even less likely to be prescribed to racial and ethnic minorities. A 2022 systematic review, for example, found that Black patients in the United States had between one-third and two-thirds the odds of being treated with the drug, compared with White patients after adjustment for potential confounders such as demographics. Hispanic/Latino patients were also less likely than Whites to be prescribed the drug.
As Dr. Holderness put it, the drug “been shown to be more effective in treatment-resistant schizophrenia than any other antipsychotic medication. Clozapine is also the most cost-effective treatment for treatment-resistant schizophrenia.” So why does this disparity exist despite clozapine’s benefits?
A 2018 systematic review of barriers to the drug’s usage identified several factors: “mandatory blood testing, fear of serious side-effects and lack of adherence by the patients, difficulty in identifying suitable patients, service fragmentation, and inadequate training in or exposure to using clozapine.” A 2016 British study, meanwhile, looked at the reasons that 45% of 316 patients stopped clozapine before 2 years. More than half of these patients stopped because of adverse effects.
Risk of neutropenia
At the APA presentation, psychiatrist Laura Clarke, MD, also of Columbia University Irving Medical Center, noted that there’s concern about one adverse effect in particular: neutropenia, or an abnormally low white blood cell count. Clozapine, she said, has a boxed warning about severe neutropenia that can lead to death.
However, she cautioned that white blood cell counts can be misleading. Some people in non-White ethnic groups have a condition known as benign ethnic neutropenia: their white blood cell counts are abnormal by the standards of people of European heritage, but they’re otherwise healthy. “These individuals do not show an increased risk of infections, and their response to infection is similar to those without them,” she said.
As many as 25%-50% of people of African ancestry may have benign ethnic neutropenia, making their blood levels appear abnormally low. Others with higher levels of the condition include certain Middle Eastern ethnicities and other ethnic groups with darker skin.
In these patents, “clinicians may avoid prescribing clozapine out of the mistaken concern that it can worsen neutropenia,” Dr. Clarke said. In fact, benign ethnic neutropenia “does not increase the risk of clozapine-induced severe neutropenia.”
Dr. Clarke highlighted drug use guidelines from the Clozapine Risk Evaluation and Mitigation Strategy, a Food and Drug Administration–mandated safety program designed to prevent severe neutropenia in patients taking clozapine. The guidelines note that the recommended absolute neutrophil count monitoring algorithm differs when patients are diagnosed with benign ethnic neutropenia.
T. Scott Stroup, MD, MPH, a psychiatrist at Columbia University, New York, urged his colleagues to consider clozapine early on in treatment-resistant schizophrenia. “Don’t go through three, four, or five antipsychotics. Even after trying two, I’d encourage people to [try clozapine].”
However, he acknowledged that “not everyone believes that. Many of my colleagues think that, before you try clozapine, you should have a trial of long-acting injectable medications to rule out pseudo–treatment resistance. I don’t totally agree with that, but I’ve more or less lost that battle,” he added.
In the big picture, Dr. Stroup said, clozapine “is good when other things aren’t working efficacy wise.”
Dr. Holderness and Dr. Clarke have no disclosures. Dr. Stroup discloses grants from the National Institutes of Health and royalties from APA Publishing and UpToDate.
SAN FRANCISCO – A trio of psychiatrists urged colleagues at the annual meeting of the American Psychiatric Association to embrace the venerable antipsychotic clozapine in patients with treatment-resistant schizophrenia. They cautioned that clinicians may overestimate the true risk of the adverse effect of neutropenia in minority populations.
“Although clozapine is known to be a life-improving and even potentially lifesaving treatment, it remains underutilized in the U.S.,” said Claire C. Holderness, MD, a psychiatrist at Columbia University Irving Medical Center, New York. “It’s been estimated that between 35% and 40% of all patients with schizophrenia should be considered for a clozapine trial. However, only 4%-5% of patients with schizophrenia in the U.S. have ever received clozapine. This is in sharp contrast to other industrialized countries where approximately 20% or more of patients with schizophrenia are treated with clozapine.”
According to Dr. Holderness, research has shown that clozapine is even less likely to be prescribed to racial and ethnic minorities. A 2022 systematic review, for example, found that Black patients in the United States had between one-third and two-thirds the odds of being treated with the drug, compared with White patients after adjustment for potential confounders such as demographics. Hispanic/Latino patients were also less likely than Whites to be prescribed the drug.
As Dr. Holderness put it, the drug “been shown to be more effective in treatment-resistant schizophrenia than any other antipsychotic medication. Clozapine is also the most cost-effective treatment for treatment-resistant schizophrenia.” So why does this disparity exist despite clozapine’s benefits?
A 2018 systematic review of barriers to the drug’s usage identified several factors: “mandatory blood testing, fear of serious side-effects and lack of adherence by the patients, difficulty in identifying suitable patients, service fragmentation, and inadequate training in or exposure to using clozapine.” A 2016 British study, meanwhile, looked at the reasons that 45% of 316 patients stopped clozapine before 2 years. More than half of these patients stopped because of adverse effects.
Risk of neutropenia
At the APA presentation, psychiatrist Laura Clarke, MD, also of Columbia University Irving Medical Center, noted that there’s concern about one adverse effect in particular: neutropenia, or an abnormally low white blood cell count. Clozapine, she said, has a boxed warning about severe neutropenia that can lead to death.
However, she cautioned that white blood cell counts can be misleading. Some people in non-White ethnic groups have a condition known as benign ethnic neutropenia: their white blood cell counts are abnormal by the standards of people of European heritage, but they’re otherwise healthy. “These individuals do not show an increased risk of infections, and their response to infection is similar to those without them,” she said.
As many as 25%-50% of people of African ancestry may have benign ethnic neutropenia, making their blood levels appear abnormally low. Others with higher levels of the condition include certain Middle Eastern ethnicities and other ethnic groups with darker skin.
In these patents, “clinicians may avoid prescribing clozapine out of the mistaken concern that it can worsen neutropenia,” Dr. Clarke said. In fact, benign ethnic neutropenia “does not increase the risk of clozapine-induced severe neutropenia.”
Dr. Clarke highlighted drug use guidelines from the Clozapine Risk Evaluation and Mitigation Strategy, a Food and Drug Administration–mandated safety program designed to prevent severe neutropenia in patients taking clozapine. The guidelines note that the recommended absolute neutrophil count monitoring algorithm differs when patients are diagnosed with benign ethnic neutropenia.
T. Scott Stroup, MD, MPH, a psychiatrist at Columbia University, New York, urged his colleagues to consider clozapine early on in treatment-resistant schizophrenia. “Don’t go through three, four, or five antipsychotics. Even after trying two, I’d encourage people to [try clozapine].”
However, he acknowledged that “not everyone believes that. Many of my colleagues think that, before you try clozapine, you should have a trial of long-acting injectable medications to rule out pseudo–treatment resistance. I don’t totally agree with that, but I’ve more or less lost that battle,” he added.
In the big picture, Dr. Stroup said, clozapine “is good when other things aren’t working efficacy wise.”
Dr. Holderness and Dr. Clarke have no disclosures. Dr. Stroup discloses grants from the National Institutes of Health and royalties from APA Publishing and UpToDate.
AT APA 2023
Higher buprenorphine doses help OUD patients stay in treatment
SAN FRANCISCO – . Eighty-five percent of patients who were titrated up to 32 mg remained in treatment for 1 year vs. 22% of those who never went higher than 16 mg, and those on higher doses stayed in treatment 3.83 times longer than those who didn’t.
“Simply put, we demonstrated better retention in treatment if patients were given higher buprenorphine doses when they complained of opioid craving,” said Andrew Gilbert, a medical student at California Northstate University, Elk Grove, Calif. He is lead author of a poster presented at the 2023 annual meeting of the American Psychiatric Association.
There’s an ongoing debate over ideal doses of buprenorphine (Suboxone), an opioid that’s used to help treat withdrawal symptoms in users of drugs such as heroin and fentanyl. Some sources recommend lower doses. The Substance Abuse and Mental Health Administration, for example, says “ideally, average dosing does not exceed 16 mg” in a guide to the drug’s usage, referring to the sublingual form. (A long-lasting injectable is also available.) Drugs.com says 24 mg is the maximum, and “higher doses have not shown a clinical advantage.
However, some emergency departments have begun providing doses up to 28 mg or higher amid the increased use of the powerful opioid fentanyl. “There are mountains of evidence demonstrating the safety of higher doses at 32 mg, and even several-fold higher than that,” study coauthor Phillip Summers MD, MPH, medical director of the harm-reduction organization Safer Alternatives Thru Networking and Education, Sacramento, Calif., said in an interview. “The question is: Is there clinical benefit to these higher doses?”
‘Significantly higher’ retention
For the new study, researchers tracked 328 patients who were treated for opioid use disorder at the Transitions Buprenorphine Clinic of Sacramento from 2010 to 2017. They were followed until 2022. Their average age was 36, 37.2% were female, 75.0% were White, and 24.1% had a history of overdose.
Clinicians titrated up the doses of buprenorphine to address withdrawal and craving. Five patients never went past 4 mg, and two of them stayed in treatment for a year. Nine of 19 who went up to 8 mg stayed in treatment for 1 year, and 4 of 21 did among those who reached 12 mg.
“Our data suggest that the highest rate of patient dropout is at the beginning of treatment, and that there is significantly higher treatment retention in patients on greater than 24 mg or higher of buprenorphine,” the researchers wrote.
Mr. Gilbert said clinicians start at 8 mg the first day in patients who haven’t taken buprenorphine before, then they go to 16 mg the second day. “We then reevaluate in at least 1 week, oftentimes sooner if the patient’s opioid craving is uncontrolled, and determine if 16 mg is too low, too high, or the correct dosage for the patient.”
If a dose of over 32 mg is needed, clinicians turn to the long-lasting injectable form of the drug, study coauthor Neil Flynn MD, MPH, former medical director of the Transitions Buprenorphine Clinic of Sacramento, said in an interview. “We controlled craving with this form for every patient that did not have opioid craving relief with 32 mg. We believe this form achieved opioid craving cessation due to increased buprenorphine blood levels and increased ratio of unmetabolized buprenorphine to metabolized buprenorphine in our patients.”
According to Dr. Summers, it’s clear that too-low doses hurt the recovery process. “If we prescribe subtherapeutic doses of buprenorphine, our patients will experience opioid craving, which leads to treatment dropout and most likely to relapse. Higher doses of buprenorphine are more likely to cease opioid cravings, leading patients to remain in treatment for longer periods of time.”
Mr. Gilbert said buprenorphine has few side effects, which include decreased libido and hot flashes in both men and women. Testosterone therapy can relieve these symptoms in men, he said, but “unfortunately, we do not have any good medications for reversing this side effect in women. Further research should investigate eliminating this side effect in women.”
Mr. Gilbert declined to comment on the extra cost of higher doses since that is outside the scope of the study.
Medication is the ‘star’
In an interview, addiction specialist Dave Cundiff, MD, MPH, of Ilwaco, Wash., praised the study and agreed with its conclusions about the value of high doses of buprenorphine.
“They’re confirming what the science has already shown, but the world does not accept,” he said, adding that “for opioid use disorder, the medication is the star of the show, although counseling is a necessary adjunct for some patients.”
Dr. Cundiff said he’s coauthored a pending review article that finds that studies support higher doses of buprenorphine.
MaryAnne Murray, DNP, EdD, MBA, a psychiatric mental health nurse practitioner who’s married to Dr. Cundiff, said in an interview that the evolution of the opioid epidemic supports the use of higher doses. “The old way we used to do with heroin users was to wait until they’re in moderate withdrawal, and then start up buprenorphine, usually slowly. With fentanyl, it takes longer, and the wait is often less bearable – unbearable for many people.”
Transitions Buprenorphine Clinic of Sacramento funded the study. The authors, Dr. Cundiff, and Dr. Murray have no disclosures.
SAN FRANCISCO – . Eighty-five percent of patients who were titrated up to 32 mg remained in treatment for 1 year vs. 22% of those who never went higher than 16 mg, and those on higher doses stayed in treatment 3.83 times longer than those who didn’t.
“Simply put, we demonstrated better retention in treatment if patients were given higher buprenorphine doses when they complained of opioid craving,” said Andrew Gilbert, a medical student at California Northstate University, Elk Grove, Calif. He is lead author of a poster presented at the 2023 annual meeting of the American Psychiatric Association.
There’s an ongoing debate over ideal doses of buprenorphine (Suboxone), an opioid that’s used to help treat withdrawal symptoms in users of drugs such as heroin and fentanyl. Some sources recommend lower doses. The Substance Abuse and Mental Health Administration, for example, says “ideally, average dosing does not exceed 16 mg” in a guide to the drug’s usage, referring to the sublingual form. (A long-lasting injectable is also available.) Drugs.com says 24 mg is the maximum, and “higher doses have not shown a clinical advantage.
However, some emergency departments have begun providing doses up to 28 mg or higher amid the increased use of the powerful opioid fentanyl. “There are mountains of evidence demonstrating the safety of higher doses at 32 mg, and even several-fold higher than that,” study coauthor Phillip Summers MD, MPH, medical director of the harm-reduction organization Safer Alternatives Thru Networking and Education, Sacramento, Calif., said in an interview. “The question is: Is there clinical benefit to these higher doses?”
‘Significantly higher’ retention
For the new study, researchers tracked 328 patients who were treated for opioid use disorder at the Transitions Buprenorphine Clinic of Sacramento from 2010 to 2017. They were followed until 2022. Their average age was 36, 37.2% were female, 75.0% were White, and 24.1% had a history of overdose.
Clinicians titrated up the doses of buprenorphine to address withdrawal and craving. Five patients never went past 4 mg, and two of them stayed in treatment for a year. Nine of 19 who went up to 8 mg stayed in treatment for 1 year, and 4 of 21 did among those who reached 12 mg.
“Our data suggest that the highest rate of patient dropout is at the beginning of treatment, and that there is significantly higher treatment retention in patients on greater than 24 mg or higher of buprenorphine,” the researchers wrote.
Mr. Gilbert said clinicians start at 8 mg the first day in patients who haven’t taken buprenorphine before, then they go to 16 mg the second day. “We then reevaluate in at least 1 week, oftentimes sooner if the patient’s opioid craving is uncontrolled, and determine if 16 mg is too low, too high, or the correct dosage for the patient.”
If a dose of over 32 mg is needed, clinicians turn to the long-lasting injectable form of the drug, study coauthor Neil Flynn MD, MPH, former medical director of the Transitions Buprenorphine Clinic of Sacramento, said in an interview. “We controlled craving with this form for every patient that did not have opioid craving relief with 32 mg. We believe this form achieved opioid craving cessation due to increased buprenorphine blood levels and increased ratio of unmetabolized buprenorphine to metabolized buprenorphine in our patients.”
According to Dr. Summers, it’s clear that too-low doses hurt the recovery process. “If we prescribe subtherapeutic doses of buprenorphine, our patients will experience opioid craving, which leads to treatment dropout and most likely to relapse. Higher doses of buprenorphine are more likely to cease opioid cravings, leading patients to remain in treatment for longer periods of time.”
Mr. Gilbert said buprenorphine has few side effects, which include decreased libido and hot flashes in both men and women. Testosterone therapy can relieve these symptoms in men, he said, but “unfortunately, we do not have any good medications for reversing this side effect in women. Further research should investigate eliminating this side effect in women.”
Mr. Gilbert declined to comment on the extra cost of higher doses since that is outside the scope of the study.
Medication is the ‘star’
In an interview, addiction specialist Dave Cundiff, MD, MPH, of Ilwaco, Wash., praised the study and agreed with its conclusions about the value of high doses of buprenorphine.
“They’re confirming what the science has already shown, but the world does not accept,” he said, adding that “for opioid use disorder, the medication is the star of the show, although counseling is a necessary adjunct for some patients.”
Dr. Cundiff said he’s coauthored a pending review article that finds that studies support higher doses of buprenorphine.
MaryAnne Murray, DNP, EdD, MBA, a psychiatric mental health nurse practitioner who’s married to Dr. Cundiff, said in an interview that the evolution of the opioid epidemic supports the use of higher doses. “The old way we used to do with heroin users was to wait until they’re in moderate withdrawal, and then start up buprenorphine, usually slowly. With fentanyl, it takes longer, and the wait is often less bearable – unbearable for many people.”
Transitions Buprenorphine Clinic of Sacramento funded the study. The authors, Dr. Cundiff, and Dr. Murray have no disclosures.
SAN FRANCISCO – . Eighty-five percent of patients who were titrated up to 32 mg remained in treatment for 1 year vs. 22% of those who never went higher than 16 mg, and those on higher doses stayed in treatment 3.83 times longer than those who didn’t.
“Simply put, we demonstrated better retention in treatment if patients were given higher buprenorphine doses when they complained of opioid craving,” said Andrew Gilbert, a medical student at California Northstate University, Elk Grove, Calif. He is lead author of a poster presented at the 2023 annual meeting of the American Psychiatric Association.
There’s an ongoing debate over ideal doses of buprenorphine (Suboxone), an opioid that’s used to help treat withdrawal symptoms in users of drugs such as heroin and fentanyl. Some sources recommend lower doses. The Substance Abuse and Mental Health Administration, for example, says “ideally, average dosing does not exceed 16 mg” in a guide to the drug’s usage, referring to the sublingual form. (A long-lasting injectable is also available.) Drugs.com says 24 mg is the maximum, and “higher doses have not shown a clinical advantage.
However, some emergency departments have begun providing doses up to 28 mg or higher amid the increased use of the powerful opioid fentanyl. “There are mountains of evidence demonstrating the safety of higher doses at 32 mg, and even several-fold higher than that,” study coauthor Phillip Summers MD, MPH, medical director of the harm-reduction organization Safer Alternatives Thru Networking and Education, Sacramento, Calif., said in an interview. “The question is: Is there clinical benefit to these higher doses?”
‘Significantly higher’ retention
For the new study, researchers tracked 328 patients who were treated for opioid use disorder at the Transitions Buprenorphine Clinic of Sacramento from 2010 to 2017. They were followed until 2022. Their average age was 36, 37.2% were female, 75.0% were White, and 24.1% had a history of overdose.
Clinicians titrated up the doses of buprenorphine to address withdrawal and craving. Five patients never went past 4 mg, and two of them stayed in treatment for a year. Nine of 19 who went up to 8 mg stayed in treatment for 1 year, and 4 of 21 did among those who reached 12 mg.
“Our data suggest that the highest rate of patient dropout is at the beginning of treatment, and that there is significantly higher treatment retention in patients on greater than 24 mg or higher of buprenorphine,” the researchers wrote.
Mr. Gilbert said clinicians start at 8 mg the first day in patients who haven’t taken buprenorphine before, then they go to 16 mg the second day. “We then reevaluate in at least 1 week, oftentimes sooner if the patient’s opioid craving is uncontrolled, and determine if 16 mg is too low, too high, or the correct dosage for the patient.”
If a dose of over 32 mg is needed, clinicians turn to the long-lasting injectable form of the drug, study coauthor Neil Flynn MD, MPH, former medical director of the Transitions Buprenorphine Clinic of Sacramento, said in an interview. “We controlled craving with this form for every patient that did not have opioid craving relief with 32 mg. We believe this form achieved opioid craving cessation due to increased buprenorphine blood levels and increased ratio of unmetabolized buprenorphine to metabolized buprenorphine in our patients.”
According to Dr. Summers, it’s clear that too-low doses hurt the recovery process. “If we prescribe subtherapeutic doses of buprenorphine, our patients will experience opioid craving, which leads to treatment dropout and most likely to relapse. Higher doses of buprenorphine are more likely to cease opioid cravings, leading patients to remain in treatment for longer periods of time.”
Mr. Gilbert said buprenorphine has few side effects, which include decreased libido and hot flashes in both men and women. Testosterone therapy can relieve these symptoms in men, he said, but “unfortunately, we do not have any good medications for reversing this side effect in women. Further research should investigate eliminating this side effect in women.”
Mr. Gilbert declined to comment on the extra cost of higher doses since that is outside the scope of the study.
Medication is the ‘star’
In an interview, addiction specialist Dave Cundiff, MD, MPH, of Ilwaco, Wash., praised the study and agreed with its conclusions about the value of high doses of buprenorphine.
“They’re confirming what the science has already shown, but the world does not accept,” he said, adding that “for opioid use disorder, the medication is the star of the show, although counseling is a necessary adjunct for some patients.”
Dr. Cundiff said he’s coauthored a pending review article that finds that studies support higher doses of buprenorphine.
MaryAnne Murray, DNP, EdD, MBA, a psychiatric mental health nurse practitioner who’s married to Dr. Cundiff, said in an interview that the evolution of the opioid epidemic supports the use of higher doses. “The old way we used to do with heroin users was to wait until they’re in moderate withdrawal, and then start up buprenorphine, usually slowly. With fentanyl, it takes longer, and the wait is often less bearable – unbearable for many people.”
Transitions Buprenorphine Clinic of Sacramento funded the study. The authors, Dr. Cundiff, and Dr. Murray have no disclosures.
AT APA 2023
Chemo avoidance pays off for some women with HER2+ early BC
The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).
“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.
As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.
The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
Study methods and results
At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).
At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.
The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.
Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.
In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”
Should clinicians embrace the study’s strategy, and what are the costs?
“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.
There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.
The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.
The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).
“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.
As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.
The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
Study methods and results
At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).
At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.
The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.
Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.
In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”
Should clinicians embrace the study’s strategy, and what are the costs?
“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.
There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.
The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.
The secondary primary endpoint results from the PHERgain study, presented at the annual meeting of the American Society of Clinical Oncology, provide more evidence to support a strategy that avoids chemotherapy as long as patients show signs of response to hormone therapy via PET scans. The results revealed that 98.8% (95% confidence interval, 96.3-100.0) of 86 patients who received treatment with trastuzumab and pertuzumab – but no chemotherapy – remained cancer free and alive 3 years after surgery (invasive disease–free survival).
“Only 1 out of 86 patients experience disease recurrence ... in those patients who never received chemotherapy,” said study lead author Javier Cortés, MD, PhD, an oncologist with Ramón y Cajal University Hospital, Madrid, during his presentation at the meeting.
As Dr. Cortés noted, HER2-targeted therapies such as trastuzumab have improved lifespans in women with HER2-positive early breast cancer, sparking interest in whether chemotherapy can be de-escalated. The PHERgain study examines whether it can be avoided entirely.
The primary endpoint results of the multicenter, open-label, noncomparative study were released in The Lancet Oncology in 2021.
Study methods and results
At 45 hospitals in Europe, patients with HER2-positive, stage I-IIIA, invasive, operable breast cancer were randomly assigned between 2017 and 2019 to receive chemotherapy prior to surgery (n = 71, group A) or to only receive hormone therapy with trastuzumab and pertuzumab, unless PET scans suggested they needed chemotherapy because they weren’t properly responding (n = 285, group B).
At a median follow-up of 5.7 months, 86 patients in the latter group had a pathological complete response and therefore met the first primary endpoint.
The new analysis tracked patients for 3 years after they underwent surgery (n = 63 and 267 for patients in groups A and B, respectively). As previously noted, at a median follow-up of 43.3 months (range, 2.4-63.0 months), only 1 of 86 patients in group B who didn’t receive chemotherapy had a recurrence of cancer (a locoregional ipsilateral recurrence). The 98.8% invasive disease–free survival rate was higher that what was seen for patients in group B as a whole (95.4% invasive disease–free survival, 95% CI, 92.8%-98.0%, P < .001). The 95.4% met the study’s second primary endpoint.
Treatment-related adverse events were higher in the group that received chemotherapy only (group A) versus group B (experiencing an adverse event grade of at least 3, 61.8% vs. 32.9%, respectively, P < .001; serious adverse events, 27.9% vs. 13.8%, respectively; P = .01). Those in group B who didn’t receive any chemotherapy had very few treatment-related adverse events that were considered being greater than a grade 3 (1.2%) and no treatment-related serious adverse events. The researchers reported that there were no treatment-related deaths.
In an interview, Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, and cochair of the session where the study data was presented, said the “intriguing and meaningful [findings] highlight the fact that not everyone may need chemotherapy.” In the big picture, the results reflect a movement toward “individualized, personalized medicine, and moving away from one size fits all.”
Should clinicians embrace the study’s strategy, and what are the costs?
“There may be a need for additional evaluation in a large phase 3 trial,” Dr. Kalinsky said.
There was no discussion about cost during the ASCO presentation. However, Dr. Kalinsky noted that there will be cost savings if patients don’t need chemotherapy. But he added that insurers in the United States don’t always cover the PET scans that are needed to evaluate whether patients are responding to hormone therapy.
The study is funded by Roche and sponsored by MedSIR. Dr. Cortes has multiple disclosures, including stock/other ownership in Leuko, MedSIR, and Nektar and honoraria from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and Samsung. Dr. Kalinsky has no disclosures.
AT ASCO 2023
Breast cancer: Meta-analysis supports ovarian suppression/ablation
Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.
The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.
The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.
Recently published research has supported hormone therapy targeting the ovaries in this population.
“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
Study methods and results
For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.
Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).
Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).
The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”
Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
Tamoxifen on its own seems to have powerful positive effect
The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.
The meta-analysis didn’t examine cost or cost-effectiveness.
Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.
Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.
“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”
According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”
It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.
No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.
Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.
The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.
The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.
Recently published research has supported hormone therapy targeting the ovaries in this population.
“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
Study methods and results
For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.
Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).
Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).
The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”
Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
Tamoxifen on its own seems to have powerful positive effect
The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.
The meta-analysis didn’t examine cost or cost-effectiveness.
Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.
Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.
“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”
According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”
It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.
No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.
Those who didn’t take tamoxifen – a standard treatment today – seemed to gain an especially large benefit.
The randomized studies, which included 14,999 subjects, suggest that ovarian suppression/ablation can provide a “substantial and persistent benefit for premenopausal women,” said study lead author and medical statistician Richard G. Gray, MA, MSc, of the University of Oxford (England), in a presentation at the annual meeting of the American Society of Clinical Oncology.
The study authors sought to better understand the value of ovarian suppression/ablation, which may prevent estrogen from stimulating residual cancer after treatment. According to the study abstract, premenopausal women with estrogen receptor–positive tumors may be at special risk of cancer recurrence because of this phenomenon.
Recently published research has supported hormone therapy targeting the ovaries in this population.
“Ovarian suppression with an aromatase inhibitor should become the preferred initial hormone therapy recommendation for all premenopausal women with high-risk (i.e., grade 3, T2, and age less than 35 years) estrogen receptor–positive breast cancer,” declared a 2022 editorial in the Journal of Clinical Oncology that noted the positive findings of a 13-year follow-up analysis of 2 studies.
Study methods and results
For the meta-analysis released at ASCO, researchers examined 25 trials that randomized women with breast cancer who were premenopausal. In some cases, the women went through menopause during the trials, and in some other cases, ovarian suppression/ablation brought on early menopause.
Among women who had received no chemotherapy or remained premenopausal after chemotherapy (n = 7,213), cancer recurred within 15 years in 41% of the controls and 28.9% of the ovarian suppression/ablation group, (relative risk, 0.70; 95% confidence interval, 0.63-0.78; P < .00001).
Among these same women, breast cancer mortality at 20 years was 34.7% in the controls and 23.8% in the ovarian suppression/ablation group (RR, 0.71; 95% CI, 0.62-0.81; P < .00001).
The researchers also looked at the same group of women and divided it into those who didn’t take tamoxifen (2,362) and those who did take tamoxifen (4,851). The drug is now the preferred option “for treatment of breast cancer.”
Among those who did not take tamoxifen, the recurrence rate at 15 years was 56.5% among controls versus 39.0% among those in the ovarian suppression/ablation group (RR, 0.61; 95% CI, 0.52-0.72; P < .00001). The gap shrunk in those who did take tamoxifen: recurrence occurred in 30.3% of the control group and 25.8% of the ovarian suppression/ablation group (RR, 0.80; 95% CI, 0.70-0.93; P = .002).
Tamoxifen on its own seems to have powerful positive effect
The findings suggest that tamoxifen on its own has a powerful positive effect, leaving less extra benefit for ovarian suppression/ablation to provide, said Mr. Gray.
The meta-analysis didn’t examine cost or cost-effectiveness.
Kevin Kalinsky, MD, MS, an oncologist at Emory University Hospital, Atlanta, cochair of the session where the meta-analysis data was presented, said in an interview that the new research shows that “patients can really benefit from ovarian function suppression.” Even so, recent trials suggested that the strategy is uncommon, used by less than 20% of high-risk patients.
Dr. Kalinsky noted that suppressing the ovaries with medication or removing the ovaries entirely can cause early menopause and eliminate fertility.
“There can be definitely be side effects like hot flashes and tolerability issues,” he said, “along with an impact on quality of life.”
According to the U.K. organization Breast Cancer Now,“ovarian suppression achieved by hormone therapy or surgery is more likely to cause menopausal symptoms than a natural menopause.” In addition, “research has shown that younger women are more likely to stop taking hormone therapy early if they don’t get help with possible side effects.”
It’s important for patients and providers to have full discussions about possible strategies, Dr. Kalinsky said.
No information about study funding was provided. Dr. Kalinsky and Mr. Gray had no financial conflicts.
AT ASCO 2023
Buprenorphine update: Looser rules and a helpful injectable
SAN FRANCISCO – As the opioid epidemic continues to grow and evolve, the federal government is trying to make it easier for clinicians to treat abusers with the drug buprenorphine, psychiatrists told colleagues at the annual meeting of the American Psychiatric Association. And an injectable version of the drug is making a big difference.
John A. Renner Jr., MD, of Boston University, said in a presentation at the APA meeting.
As Dr. Renner explained, the United States is now in the fourth wave of nearly a quarter-century of opioid overdose-related deaths. The outbreak began in 1999 as prescription opioids spurred deaths, and heroin overdoses began to rise in 2010. The third wave brought rises in deaths from synthetic opioids such as fentanyl in 2013. In 2015, the fourth wave – driven by deaths from combinations of synthetic opioids and psychostimulants like methamphetamines – started in 2015.
COVID-19 seems to have played a role too: In 2020, opioid overdose deaths spiked during the early months of the pandemic. In 2021, drug-related overdose deaths overall hit a high of 106,889, including 80,411 linked to opioids. In contrast, fewer than 20,000 drug-related overdose deaths were reported in 1999.
On the other hand, deaths from prescription drug overdoses are falling, Dr. Renner said, suggesting “improvement in terms of how clinicians are handling medications and our prescribing practices. But that’s being masked by what’s happened with fentanyl and methamphetamine.”
Buprenorphine (Subutex), used to treat opioid use withdrawal, is itself an opioid and can cause addiction and death in some cases. However, Dr. Renner highlighted a 2023 study that determined that efforts to increase its use from 2019 to 2021 didn’t appear to boost buprenorphine-related overdose deaths in the United States.
New federal regulations aim to make it easier to prescribe buprenorphine. Thanks to Congressional legislation, the Drug Enforcement Administration in January 2023 eliminated regulations requiring clinicians to undergo special training to get an “X-waiver” to be able to prescribe buprenorphine. But they’re not off the hook entirely: As of June 27, 2023, providers must have undergone training in order to apply for – or renew – a DEA license to prescribe certain controlled substances like buprenorphine.
“I’m afraid that people will be able to meet that requirement easily, and they’re not going to get good coordinated teaching,” Dr. Renner said. “I’m not sure that’s really going to improve the quality of care that we’re delivering.”
In regard to treatment, psychiatrist Dong Chan Park, MD, of Boston University, touted a long-acting injectable form of buprenorphine known by the brand name Sublocade. The FDA approved Sublocade in 2017 for patients who’ve been taking sublingual buprenorphine for at least 7 days, although Dr. Park said research suggests the 7-day period may not be necessary.
“We’ve utilized this about 2.5-plus years in my hospital, and it’s really been a game changer for some of our sickest, most challenging patients,” he said at the APA presentation. As he explained, one benefit is that patients can’t repeatedly avoid doses depending on how they feel, as they may do with the sublingual version. “On the first day of injection, you can actually stop the sublingual buprenorphine.”
Dr. Renner emphasized the importance of getting users on buprenorphine as fast as possible. If the treatment begins in the ED, he said, “they need to have a system that is going to be able to pick them up and continue the care.”
Otherwise, the risk is high. “We’re in a very dangerous era,” he said, “where the patient walks out the door, and then they die.”
Dr. Park had no disclosures, and Dr. Renner disclosed royalties from the APA.
SAN FRANCISCO – As the opioid epidemic continues to grow and evolve, the federal government is trying to make it easier for clinicians to treat abusers with the drug buprenorphine, psychiatrists told colleagues at the annual meeting of the American Psychiatric Association. And an injectable version of the drug is making a big difference.
John A. Renner Jr., MD, of Boston University, said in a presentation at the APA meeting.
As Dr. Renner explained, the United States is now in the fourth wave of nearly a quarter-century of opioid overdose-related deaths. The outbreak began in 1999 as prescription opioids spurred deaths, and heroin overdoses began to rise in 2010. The third wave brought rises in deaths from synthetic opioids such as fentanyl in 2013. In 2015, the fourth wave – driven by deaths from combinations of synthetic opioids and psychostimulants like methamphetamines – started in 2015.
COVID-19 seems to have played a role too: In 2020, opioid overdose deaths spiked during the early months of the pandemic. In 2021, drug-related overdose deaths overall hit a high of 106,889, including 80,411 linked to opioids. In contrast, fewer than 20,000 drug-related overdose deaths were reported in 1999.
On the other hand, deaths from prescription drug overdoses are falling, Dr. Renner said, suggesting “improvement in terms of how clinicians are handling medications and our prescribing practices. But that’s being masked by what’s happened with fentanyl and methamphetamine.”
Buprenorphine (Subutex), used to treat opioid use withdrawal, is itself an opioid and can cause addiction and death in some cases. However, Dr. Renner highlighted a 2023 study that determined that efforts to increase its use from 2019 to 2021 didn’t appear to boost buprenorphine-related overdose deaths in the United States.
New federal regulations aim to make it easier to prescribe buprenorphine. Thanks to Congressional legislation, the Drug Enforcement Administration in January 2023 eliminated regulations requiring clinicians to undergo special training to get an “X-waiver” to be able to prescribe buprenorphine. But they’re not off the hook entirely: As of June 27, 2023, providers must have undergone training in order to apply for – or renew – a DEA license to prescribe certain controlled substances like buprenorphine.
“I’m afraid that people will be able to meet that requirement easily, and they’re not going to get good coordinated teaching,” Dr. Renner said. “I’m not sure that’s really going to improve the quality of care that we’re delivering.”
In regard to treatment, psychiatrist Dong Chan Park, MD, of Boston University, touted a long-acting injectable form of buprenorphine known by the brand name Sublocade. The FDA approved Sublocade in 2017 for patients who’ve been taking sublingual buprenorphine for at least 7 days, although Dr. Park said research suggests the 7-day period may not be necessary.
“We’ve utilized this about 2.5-plus years in my hospital, and it’s really been a game changer for some of our sickest, most challenging patients,” he said at the APA presentation. As he explained, one benefit is that patients can’t repeatedly avoid doses depending on how they feel, as they may do with the sublingual version. “On the first day of injection, you can actually stop the sublingual buprenorphine.”
Dr. Renner emphasized the importance of getting users on buprenorphine as fast as possible. If the treatment begins in the ED, he said, “they need to have a system that is going to be able to pick them up and continue the care.”
Otherwise, the risk is high. “We’re in a very dangerous era,” he said, “where the patient walks out the door, and then they die.”
Dr. Park had no disclosures, and Dr. Renner disclosed royalties from the APA.
SAN FRANCISCO – As the opioid epidemic continues to grow and evolve, the federal government is trying to make it easier for clinicians to treat abusers with the drug buprenorphine, psychiatrists told colleagues at the annual meeting of the American Psychiatric Association. And an injectable version of the drug is making a big difference.
John A. Renner Jr., MD, of Boston University, said in a presentation at the APA meeting.
As Dr. Renner explained, the United States is now in the fourth wave of nearly a quarter-century of opioid overdose-related deaths. The outbreak began in 1999 as prescription opioids spurred deaths, and heroin overdoses began to rise in 2010. The third wave brought rises in deaths from synthetic opioids such as fentanyl in 2013. In 2015, the fourth wave – driven by deaths from combinations of synthetic opioids and psychostimulants like methamphetamines – started in 2015.
COVID-19 seems to have played a role too: In 2020, opioid overdose deaths spiked during the early months of the pandemic. In 2021, drug-related overdose deaths overall hit a high of 106,889, including 80,411 linked to opioids. In contrast, fewer than 20,000 drug-related overdose deaths were reported in 1999.
On the other hand, deaths from prescription drug overdoses are falling, Dr. Renner said, suggesting “improvement in terms of how clinicians are handling medications and our prescribing practices. But that’s being masked by what’s happened with fentanyl and methamphetamine.”
Buprenorphine (Subutex), used to treat opioid use withdrawal, is itself an opioid and can cause addiction and death in some cases. However, Dr. Renner highlighted a 2023 study that determined that efforts to increase its use from 2019 to 2021 didn’t appear to boost buprenorphine-related overdose deaths in the United States.
New federal regulations aim to make it easier to prescribe buprenorphine. Thanks to Congressional legislation, the Drug Enforcement Administration in January 2023 eliminated regulations requiring clinicians to undergo special training to get an “X-waiver” to be able to prescribe buprenorphine. But they’re not off the hook entirely: As of June 27, 2023, providers must have undergone training in order to apply for – or renew – a DEA license to prescribe certain controlled substances like buprenorphine.
“I’m afraid that people will be able to meet that requirement easily, and they’re not going to get good coordinated teaching,” Dr. Renner said. “I’m not sure that’s really going to improve the quality of care that we’re delivering.”
In regard to treatment, psychiatrist Dong Chan Park, MD, of Boston University, touted a long-acting injectable form of buprenorphine known by the brand name Sublocade. The FDA approved Sublocade in 2017 for patients who’ve been taking sublingual buprenorphine for at least 7 days, although Dr. Park said research suggests the 7-day period may not be necessary.
“We’ve utilized this about 2.5-plus years in my hospital, and it’s really been a game changer for some of our sickest, most challenging patients,” he said at the APA presentation. As he explained, one benefit is that patients can’t repeatedly avoid doses depending on how they feel, as they may do with the sublingual version. “On the first day of injection, you can actually stop the sublingual buprenorphine.”
Dr. Renner emphasized the importance of getting users on buprenorphine as fast as possible. If the treatment begins in the ED, he said, “they need to have a system that is going to be able to pick them up and continue the care.”
Otherwise, the risk is high. “We’re in a very dangerous era,” he said, “where the patient walks out the door, and then they die.”
Dr. Park had no disclosures, and Dr. Renner disclosed royalties from the APA.
AT APA 2023