AVAHO

Patients often come to us with questions about vitamin and mineral supplements. Sometimes they come to us with bags full of the things they are taking. The Internet is full of the wonders these nutritional supplements can do, from turmeric curing cancer to vitamin D curing COVID. It is hard to keep up with medicine itself without learning a whole new field of nutritional supplements.

However, for cardiovascular disease (CVD) and cancer prevention, the answer is pretty easy according to USPSTF (United States Preventative Services Task Force) guidelines. They evaluated 17,459 unique citations as well as 379 full-text articles that included randomized clinical trials and observational cohort studies. The conclusions of their research showed that there was little to no benefit in taking vitamin or mineral supplements to prevent CVD, cancer, or death. In fact, beta-carotene supplementation was associated with increased risk of lung cancer and other adverse outcomes in patients at increased risk of lung cancer.

Although they are often marketed like drugs, nutritional supplements are regulated as foods, with less stringent standards.* Our current medical culture pushes us to practice evidence-based medicine. Without evidence, we simply cannot counsel patients about supplements because there is little evidence to support their use.

Additionally, many patients assume that they are safe. While this may be true for many of them, some of them can be harmful in several ways. They can interact with medications the patient may be taking for medical conditions. Some of them have been shown to cause liver and other organ damage. When they are used to replace traditional medicine, they can also lead to harm by delaying appropriate medical care. For example, a patient who believes a supplement can treat cancer when it does nothing is delaying care that might save their life. By the time they realize it is not working, the cancer may have advanced too far to be treatable.

While there may be a few studies that do show some efficacy for vitamins and minerals in certain diseases, these guidelines are looking only at use in terms of preventing cancer and CVD. As primary care physicians, we all know the screening guidelines for cancer prevention. We are better off recommending screening mammograms and colon cancer screening tests. And we all know the risk factors for CVD and how to mitigate these risks.

What can we do when patients come to us with false claims regarding supplements?

• Hear what they are saying. They don’t know who to trust. We will never become their trusted source of medical information if we don’t listen to their concerns.
• Answer their questions, no matter how ridiculous they may seem to us. Many people who sell supplements sound convincing. That is how they sell their products. Our advice may seem just as ridiculous to them. We need to explain the facts clearly and be sure the patient understands.
• Give the patient resources. Know what websites to direct them to so that they can get accurate information.
• Know what’s out there. I was once surprised when a patient told me she was going to try turmeric as a treatment for uterine cancer. We cannot combat misinformation when we don’t know what’s being said.
• Become a voice for medical information. There is so much misinformation being spread. We need more doctors to speak up about the right medical information.

Currently, patients often look for medical information online. We do them a disservice when we brush aside their questions regarding supplements, no matter how trivial they seem. We need to take a firm stand and tell them the evidence regarding these supplements: They are neither FDA approved nor studied for safety and efficacy. Anyone can sell a supplement and make any claim regarding it that they want. It is much better to eat a healthy, balanced diet to get the vitamins and minerals that you need. Not only do we need to show them the evidence, we need to convince them that it is true.

*Correction, 12/4: An earlier version of this article misstated the regulatory requirements for nutritional supplements.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She was paid by Pfizer as a consultant on Paxlovid and is the editor in chief of Physician’s Weekly.

Patients often come to us with questions about vitamin and mineral supplements. Sometimes they come to us with bags full of the things they are taking. The Internet is full of the wonders these nutritional supplements can do, from turmeric curing cancer to vitamin D curing COVID. It is hard to keep up with medicine itself without learning a whole new field of nutritional supplements.

However, for cardiovascular disease (CVD) and cancer prevention, the answer is pretty easy according to USPSTF (United States Preventative Services Task Force) guidelines. They evaluated 17,459 unique citations as well as 379 full-text articles that included randomized clinical trials and observational cohort studies. The conclusions of their research showed that there was little to no benefit in taking vitamin or mineral supplements to prevent CVD, cancer, or death. In fact, beta-carotene supplementation was associated with increased risk of lung cancer and other adverse outcomes in patients at increased risk of lung cancer.

Although they are often marketed like drugs, nutritional supplements are regulated as foods, with less stringent standards.* Our current medical culture pushes us to practice evidence-based medicine. Without evidence, we simply cannot counsel patients about supplements because there is little evidence to support their use.

Additionally, many patients assume that they are safe. While this may be true for many of them, some of them can be harmful in several ways. They can interact with medications the patient may be taking for medical conditions. Some of them have been shown to cause liver and other organ damage. When they are used to replace traditional medicine, they can also lead to harm by delaying appropriate medical care. For example, a patient who believes a supplement can treat cancer when it does nothing is delaying care that might save their life. By the time they realize it is not working, the cancer may have advanced too far to be treatable.

While there may be a few studies that do show some efficacy for vitamins and minerals in certain diseases, these guidelines are looking only at use in terms of preventing cancer and CVD. As primary care physicians, we all know the screening guidelines for cancer prevention. We are better off recommending screening mammograms and colon cancer screening tests. And we all know the risk factors for CVD and how to mitigate these risks.

What can we do when patients come to us with false claims regarding supplements?

• Hear what they are saying. They don’t know who to trust. We will never become their trusted source of medical information if we don’t listen to their concerns.
• Answer their questions, no matter how ridiculous they may seem to us. Many people who sell supplements sound convincing. That is how they sell their products. Our advice may seem just as ridiculous to them. We need to explain the facts clearly and be sure the patient understands.
• Give the patient resources. Know what websites to direct them to so that they can get accurate information.
• Know what’s out there. I was once surprised when a patient told me she was going to try turmeric as a treatment for uterine cancer. We cannot combat misinformation when we don’t know what’s being said.
• Become a voice for medical information. There is so much misinformation being spread. We need more doctors to speak up about the right medical information.

Currently, patients often look for medical information online. We do them a disservice when we brush aside their questions regarding supplements, no matter how trivial they seem. We need to take a firm stand and tell them the evidence regarding these supplements: They are neither FDA approved nor studied for safety and efficacy. Anyone can sell a supplement and make any claim regarding it that they want. It is much better to eat a healthy, balanced diet to get the vitamins and minerals that you need. Not only do we need to show them the evidence, we need to convince them that it is true.

*Correction, 12/4: An earlier version of this article misstated the regulatory requirements for nutritional supplements.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She was paid by Pfizer as a consultant on Paxlovid and is the editor in chief of Physician’s Weekly.

Patients often come to us with questions about vitamin and mineral supplements. Sometimes they come to us with bags full of the things they are taking. The Internet is full of the wonders these nutritional supplements can do, from turmeric curing cancer to vitamin D curing COVID. It is hard to keep up with medicine itself without learning a whole new field of nutritional supplements.

However, for cardiovascular disease (CVD) and cancer prevention, the answer is pretty easy according to USPSTF (United States Preventative Services Task Force) guidelines. They evaluated 17,459 unique citations as well as 379 full-text articles that included randomized clinical trials and observational cohort studies. The conclusions of their research showed that there was little to no benefit in taking vitamin or mineral supplements to prevent CVD, cancer, or death. In fact, beta-carotene supplementation was associated with increased risk of lung cancer and other adverse outcomes in patients at increased risk of lung cancer.

Although they are often marketed like drugs, nutritional supplements are regulated as foods, with less stringent standards.* Our current medical culture pushes us to practice evidence-based medicine. Without evidence, we simply cannot counsel patients about supplements because there is little evidence to support their use.

Additionally, many patients assume that they are safe. While this may be true for many of them, some of them can be harmful in several ways. They can interact with medications the patient may be taking for medical conditions. Some of them have been shown to cause liver and other organ damage. When they are used to replace traditional medicine, they can also lead to harm by delaying appropriate medical care. For example, a patient who believes a supplement can treat cancer when it does nothing is delaying care that might save their life. By the time they realize it is not working, the cancer may have advanced too far to be treatable.

While there may be a few studies that do show some efficacy for vitamins and minerals in certain diseases, these guidelines are looking only at use in terms of preventing cancer and CVD. As primary care physicians, we all know the screening guidelines for cancer prevention. We are better off recommending screening mammograms and colon cancer screening tests. And we all know the risk factors for CVD and how to mitigate these risks.

What can we do when patients come to us with false claims regarding supplements?

• Hear what they are saying. They don’t know who to trust. We will never become their trusted source of medical information if we don’t listen to their concerns.
• Answer their questions, no matter how ridiculous they may seem to us. Many people who sell supplements sound convincing. That is how they sell their products. Our advice may seem just as ridiculous to them. We need to explain the facts clearly and be sure the patient understands.
• Give the patient resources. Know what websites to direct them to so that they can get accurate information.
• Know what’s out there. I was once surprised when a patient told me she was going to try turmeric as a treatment for uterine cancer. We cannot combat misinformation when we don’t know what’s being said.
• Become a voice for medical information. There is so much misinformation being spread. We need more doctors to speak up about the right medical information.

Currently, patients often look for medical information online. We do them a disservice when we brush aside their questions regarding supplements, no matter how trivial they seem. We need to take a firm stand and tell them the evidence regarding these supplements: They are neither FDA approved nor studied for safety and efficacy. Anyone can sell a supplement and make any claim regarding it that they want. It is much better to eat a healthy, balanced diet to get the vitamins and minerals that you need. Not only do we need to show them the evidence, we need to convince them that it is true.

*Correction, 12/4: An earlier version of this article misstated the regulatory requirements for nutritional supplements.

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. She was paid by Pfizer as a consultant on Paxlovid and is the editor in chief of Physician’s Weekly.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

SAN DIEGO – The Food and Drug Administration has launched Project Optimus to dramatically overhaul how oncology therapies are developed in clinical trials, with investigational blood cancer drugs taking center stage in this effort.

The goal is “to better identify and characterize optimized doses” in early stages of research and move away from the default of the traditional maximum tolerated dose strategy, hematologist-oncologist Marc R. Theoret, MD, deputy director of the FDA’s Oncology Center of Excellence, said in a presentation at the 2023 Society for Immunotherapy of Cancer annual meeting.

Earlier this year, the FDA released a draft guidance regarding the changes it hopes to see. The agency supported randomized, parallel dose-response trials when feasible, and “strong rationale for choice of dosage should be provided before initiating a registration trial(s) to support a subsequent indication and usage.”

The goal of controlling toxicity is “very highly important” in hematology research since blood cancer drugs can cause significant adverse effects in areas such as the lungs and heart, said Cecilia Yeung, MD, who led the SITC session about Project Optimus. Dr. Yeung is a clinical pathologist who works on investigational trials at Fred Hutchinson Cancer Research Center in Seattle.

In an interview, Dr. Yeung, who has a subspecialty in hematopathology, explained why the foundations of cancer research are changing and what hematologist-oncologists can expect to see on the horizon.
 

Q: Project Optimus aims to move beyond the traditional dose-escalation approach to the development of cancer drugs. How does that strategy work?

Dr. Yeung: Prior to Project Optimus, they’d use a 3+3 strategy in phase 1 trials: They’d give a dose to three fairly healthy patients, then they’d go up by escalating doses in more patients. They’d keep going up until two-thirds of patients at a specific dose suffered from bad side effects, then they’d back off to the last dose.

Q: This approach, which aims to identify the “maximum tolerated dose,” seemed to work well over decades of research into chemotherapy drugs. But worries arose as targeted therapies appeared in oncology areas such as blood cancer. Why did things change?

Dr. Yeung: With 3+3, you could tell pretty quickly how toxic chemotherapy was. But in targeted therapy, we were finding that these studies are not representative of actual toxicity. You’re not treating these patients for a very long time in phase 1, while patients on targeted therapy may be on these drugs for years. Concerns actually started with the first targeted drugs to treat leukemias and lymphomas. They were shown to have unexpected toxicity. A 2016 study found that drug developers had to reduce the original phase 1 dose in 45% of phase 3 trials [of small molecule and monoclonal antibody targeted agents] approved by the FDA over 12 years because of toxicity.

Q: What is FDA’s goal for Project Optimus?

Dr. Yeung: They want to have a second piece, to balance that maximum tolerated dose with a safe and tolerable dose for most people.

Q: What kind of resistance is the FDA getting from drug companies?

Dr. Yeung: The FDA makes a good argument that the system wasn’t working. But drug companies say this will drive up the cost of clinical trials and won’t allow them to treat patients with the maximal doses they could give them. I see arguments from both sides. There has to be a balance between the two.

Q: How will all this affect drug development?

Dr. Yeung: Drugs may become more expensive because much more testing will happen during clinical trials.

Q: Could this reduce the number of investigational drugs?

Dr. Yeung: Hopefully not, but this is huge endeavor for smaller companies that are strapped for funding.

Q: What do you think the future holds?

Dr. Yeung: Ultimately, this is a good thing because if everything works out, we’ll have fewer toxic side effects. But we’re going to have to go through a period of growing pains.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Older adults with actinic keratoses (AKs) have a higher risk for skin cancers, including squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and melanoma.

METHODOLOGY:

• AKs have been associated with a small risk for cutaneous SCC, but associations with risk for other skin cancers have not been well studied.
• AKs may be a marker of overall skin cancer risk, but guidelines for AK management lack recommendations for follow-up cancer surveillance.
• The researchers reviewed data from a random sample of 5 million fee-for-service Medicare beneficiaries treated for AKs from 2009 through 2018 in the United States. Patients with seborrheic keratoses (SKs) were included as comparators, and patients with a history of skin cancer were excluded.
• The primary outcome was the first surgically treated skin cancer, including SCC, BCC, and melanoma.

TAKEAWAY:

• A total of 555,945 adults with AKs and 481,024 with SKs were included. The mean age was approximately 74.0 years. More than half were female. Most were non-Hispanic White.
• Among patients with AKs, the absolute risk for any skin cancer after the first AK was 6.3%, 18.4%, and 28.5% at 1, 3, and 5 years, respectively.
• Patients with AKs had a significantly increased relative risk for any skin cancer compared with those with SKs (adjusted hazard ratio [aHR], 2.17) and separately for keratinocyte carcinoma (aHR, 2.20), SCC (aHR, 2.63), BCC (aHR, 1.85), and melanoma (aHR, 1.67).
• Although AKs are not considered a biological precursor of melanoma or BCC, the results suggest that AKs may be clinical indicators of increased UV exposure that subsequently increases the risk for skin cancer.

IN PRACTICE:

“The present results highlight the importance of developing evidence-based guidelines for follow-up skin cancer surveillance in patients with AKs, optimally including measures of AK burden,” the researchers wrote.

SOURCE:

The lead author on the study was Cassandra Mohr, BS, with corresponding author Mackenzie R. Wehner, MD, MPhil, of The University of Texas MD Anderson Cancer Center, Houston. The study was published online in JAMA Dermatology .

LIMITATIONS:

The study population of Medicare beneficiaries aged 65 years or older may not be a nationally representative sample, and surveillance bias may contribute to the increased risk for skin cancer in patients with AKs. The use of both ICD and CPT codes may underestimate the number of skin cancers because of cases that were treated nonsurgically.

DISCLOSURES:

The study was supported by the National Cancer Institute of the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and The University of Texas Rising STARS program. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

TOPLINE:

Incipient ulceration in primary cutaneous melanoma may represent a more biologically aggressive disease population than truly nonulcerated tumors.

METHODOLOGY:

• The final cohort included 40 cases of incipient ulceration that were matched 1:2 with 80 nonulcerated controls and 80 ulcerated controls.
• The prognostic significance of incipient ulceration in cutaneous melanoma is unclear.
• Current American Joint Committee on Cancer (AJCC) guidelines classify incipient ulceration as nonulcerated.
• In a retrospective case-control study, researchers drew from the Melanoma Institute Australia database to identify resected primary cutaneous melanomas diagnosed between 2005 and 2015 that had slides available at Royal Prince Alfred Hospital in Sydney and a Breslow thickness greater than 0 mm.
• Clinical outcomes compared between cases and controls were recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS).

TAKEAWAY:

• The median Breslow depth was 2.8 mm for incipient cases, compared with 1.0 mm for nonulcerated melanomas and 5.3 mm for ulcerated melanomas, while the median tumor mitotic rate was 5.0 per mm² for incipient cases, compared with 1 per mm² in nonulcerated controls and 9 per mm² in ulcerated controls.
• On univariable analyses, compared with patients with incipiently ulcerated cases, patients with nonulcerated tumors had significantly better OS (hazard ratio [HR], 0.49) and RFS (HR, 0.37), while patients with ulcerated tumors showed worse RFS (HR, 1.67).
• On multivariable analyses, no differences in survival outcomes were observed, perhaps due to the moderate number of incipient ulceration cases included in the study, the authors wrote.

IN PRACTICE:

“Future editions of the AJCC staging system should consider acknowledging this interpretive challenge and provide guidance on how primary melanomas with incipient ulceration should be classified,” the researchers wrote.

SOURCE:

Richard A. Scolyer, MD, a pathologist at Royal Prince Alfred Hospital, Camperdown, Australia, is the senior author on the study, which was published online in JAMA Dermatology.

LIMITATIONS:

Limitations of the study include its retrospective design and the relatively small number of cases that met criteria for inclusion.

DISCLOSURES:

Dr. Scolyer disclosed that he has received grants from the Australian National Health and Medical Research Council and personal fees from MetaOptima, F. Hoffmann-La Roche, Evaxion, Provectus, QBiotics, Novartis, Merck Sharp & Dohme, NeraCare, Amgen, Bristol-Myers Squibb, Myriad Genetics, and GlaxoSmithKline, all outside the submitted work. Four coauthors reported having received financial support outside of the submitted work.

A version of this article appeared on Medscape.com.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

Developments in early breast cancer reported at the European Society for Medical Oncology (ESMO) 2023 Congress are discussed by Dr Lisa Carey of University of North Carolina, Chapel Hill. 

Dr Carey begins with 5-year results from the KEYNOTE-522 study in patients with early triple-negative breast cancer in which the immune checkpoint inhibitor pembrolizumab was incorporated into combination therapy both pre- and postoperatively. The new findings were consistent with earlier results, showing that pembrolizumab improved pathologic complete response (pCR) and event-free survival. 

Turning to human epidermal growth factor receptor 2–positive (HER2+) disease, Dr Carey discusses the PHERGain trial's use of a genomic assay to define risk and predict pCR. She suggests that such assays could lead to tailored therapy for HER2+ patients. 

On estrogen receptor–positive (ER+)/HER2- disease, Dr Carey reports first on KEYNOTE-756, which examined the addition of pembrolizumab to combination therapy for high-risk patients in both the neoadjuvant and adjuvant settings. Pembrolizumab improved pCR compared with placebo. 

Dr Carey closes by discussing another study in high-risk ER+/HER2- disease. Similar in design to KEYNOTE-756, CheckMate 7FL found that nivolumab added to combination therapy again augmented pCR results. 

--

Lisa A. Carey, MD, Distinguished Professor or Breast Cancer Research, University of North Carolina Lineberger Comprehensive Cancer Center; Professor, Division of Medical Oncology, Bassnight North Carolina Cancer Hospital, Chapel Hill, North Carolina  

Lisa A. Carey, MD, has disclosed no relevant financial relationships.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved the biologic Adzynma (ADAMTS13, recombinant-krhn, Takeda Pharmaceuticals) to treat adults and children who have a rare and life-threatening blood clotting disorder called congenital thrombotic thrombocytopenic purpura (TTP). Adzynma is the first recombinant protein product for preventive or on-demand enzyme replacement therapy for people with the blood clotting condition.

Congenital TTP affects fewer than 1,000 people in the United States and is caused by a mutation in the ADAMTS13 gene, which makes an enzyme that regulates blood clotting. Patients with the congenital TTP typically receive prophylactic plasma-based therapy to replenish the ADAMTS13 enzyme and reduce the risk for clotting and bleeding. The condition, however, can be fatal if left untreated.

The new agent is a purified recombinant form of the ADAMTS13 enzyme that works by replacing low levels of the deficient enzyme in patients with congenital TTP. Adzynma is given prophylactically to reduce the risk for disease symptoms and on demand when a patient is experiencing an acute event, according to the FDA approval announcement.

The approval was based on a global randomized phase 3 study comparing the product with plasma-based therapies in 46 patients with congenital TTP. Patients in the trial were randomized to receive 6 months of treatment with either intravenous Adzynma — given once every other week as prophylactic enzyme replacement therapy or once daily as on-demand enzyme replacement therapy — or plasma-based therapies. The patients then crossed over to the other treatment for 6 months.

Interim findings from the study showed that Adzynma reduced the incidence of thrombocytopenia — the most common symptom of congenital TTP — by 60% compared with plasma-based therapy (rate ratio, 0.40). No patients experienced an acute TTP event during Adzynma prophylaxis, Takeda said.

Significantly more patients receiving plasma-based therapies experienced treatment-emergent adverse events compared with those receiving the biologic.

The most common side effects associated with the biologic were headache (31.3%), diarrhea (16.7%), migraine (14.6%), abdominal pain (12.5%), nausea (12.5%), upper respiratory tract infection (12.5%), dizziness (10.4%), and vomiting (10.4%). No treatment-related adverse events, including allergic reactions, were observed during administration.

“The FDA remains deeply committed in our efforts to help facilitate the development and approval of safe and effective therapies for patients with rare diseases,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, stated. The “approval reflects important progress in the development of much-needed treatment options for patients affected by this life-threatening disorder.”

A version of this article first appeared on Medscape.com.

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

Developments in metastatic breast cancer (MBC) were reported at the European Society for Medical Oncology (ESMO) 2023 Congress and are discussed by Dr Ann Partridge of Dana-Farber Cancer Institute. 

To begin, Dr Partridge highlights a late-breaking abstract showing that use of the antibody-drug conjugate (ADC) datopotamab deruxtecan in hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2-) MBC results in improved progression-free survival (PFS) compared with chemotherapy. 

Next, Dr Partridge turns to two studies on another ADC, trastuzumab deruxtecan (T-DXd), in MBC. The first study showed positive PFS and overall survival results among patients with either estrogen receptor–positive (ER+)/HER2-low or triple-negative/HER2-low breast cancer. The second T-DXd study examined the ADC's impact on brain metastases in patients with HER2+ disease and reported favorable results. 

She then highlights promising phase 2 results for a novel agent called OP-1250, or palazestrant, studied in patients with ER+/HER2- MBC. 

Finally, Dr Partridge points to a study of a supportive-care program called MOATT, designed for patients on oral MBC therapy, which aims to improve home management. Compared with local standard of care, patients in the program show higher rates of persistence in therapy management and, importantly, concomitant improvements in PFS. 

--

Ann H. Partridge, MD, Professor of Medicine, Harvard Medical School; Vice Chair of Clinical Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 

Ann H. Partridge, MD, MPH, has disclosed no relevant financial relationships. 

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

A version of this article first appeared on Medscape.com.

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

A version of this article first appeared on Medscape.com.

In patients with myocardial infarction and anemia, a “liberal” red blood cell transfusion strategy did not significantly reduce the risk of recurrent MI or death within 30 days, compared with a “restrictive” transfusion strategy, in the 3,500-patient MINT trial.

“While not statistically significant, the results consistently favored a liberal transfusion strategy,” Jeffrey L. Carson, MD, from Robert Wood Johnson Medical School, New Brunswick, N.J., said in a press briefing.

He presented the study in a late-breaking trial session at the annual scientific sessions of the American Heart Association, and it was simultaneously published online in the New England Journal of Medicine.

“Whether to transfuse is an everyday decision faced by clinicians caring for patients with acute MI,” Dr. Carson said.

“We cannot claim that a liberal transfusion strategy is definitively superior based on our primary outcome,” he said, but “the 95% confidence interval is consistent with treatment effects corresponding to no difference between the two transfusion strategies and to a clinically relevant benefit with the liberal strategy.” 

“In contrast to other trials in other settings,” such as anemia and cardiac surgery, Dr. Carson said, “the results suggest that a liberal transfusion strategy has the potential for clinical benefit with an acceptable risk of harm.”

“A liberal transfusion strategy may be the most prudent approach to transfusion in anemic patients with MI,” he added.
 

Not a home run

Others agreed with this interpretation. Martin B. Leon, MD, from Columbia University, New York, the study discussant in the press briefing, said the study “addresses a question that is common” in clinical practice. It was well conducted, and international (although most patients were in the United States and Canada), in a very broad group of patients, designed to make the results more generalizable. The 98% follow-up was extremely good, Dr. Leon added, and the trialists achieved their goal in that they did show a difference between the two transfusion strategies.

The number needed to treat was 40 to see a benefit in the combined outcome of death or recurrent MI at 30 days, Dr. Leon said. The P value for this was .07, “right on the edge” of statistical significance.

This study is “not a home run,” for the primary outcome, he noted; however, many of the outcomes tended to be in favor of a liberal transfusion strategy. Notably, cardiovascular death, which was not a specified outcome, was significantly lower in the group who received a liberal transfusion strategy.

Although a liberal transfusion strategy was “not definitely superior” in these patients with MI and anemia, Dr. Carson said, he thinks the trial will be interpreted as favoring a liberal transfusion strategy.

C. Michael Gibson, MD, professor of medicine at Harvard Medical School, Boston, and CEO of Harvard’s Baim and PERFUSE institutes for clinical research, voiced similar views.

“Given the lack of acute harm associated with liberal transfusion and the preponderance of evidence favoring liberal transfusion in the largest trial to date,” concluded Dr. Gibson, the assigned discussant at the session, “liberal transfusion appears to be a viable management strategy, particularly among patients with non-STEMI type 1 MI and as clinical judgment dictates.”

Only three small randomized controlled trials have compared transfusion thresholds in a total of 820 patients with MI and anemia, Dr. Gibson said, a point that the trial investigators also made. The results were inconsistent between trials: the CRIT trial (n = 45) favored a restrictive strategy, the MINT pilot study (n = 110) favored a liberal one, and the REALITY trial (n = 668) showed noninferiority of a restrictive strategy, compared with a liberal strategy in 30-day MACE.  

The MINT trial was four times larger than all prior studies combined. However, most outcomes were negative or of borderline significance for benefit.

Cardiac death was more common in the restrictive group at 5.5% than the liberal group at 3.2% (risk ratio, 1.74, 95% CI, 1.26-2.40), but this was nonadjudicated, and not designated as a primary, secondary, or tertiary outcome – which the researchers also noted. Fewer than half of the deaths were classified as cardiac, which was “odd,” Dr. Gibson observed.

A restrictive transfusion strategy was associated with increased events among participants with type 1 MI (RR, 1.32, 95% CI, 1.04-1.67), he noted.

Study strengths included that 45.5% of participants were women, Dr. Gibson said. Limitations included that the trial was “somewhat underpowered.” Also, even in the restrictive group, participants received a mean of 0.7 units of packed red blood cells.

Adherence to the 10 g/dL threshold in the liberal transfusion group was moderate (86.3% at hospital discharge), which the researchers acknowledged. They noted that this was frequently caused by clinical discretion, such as concern about fluid overload, and to the timing of hospital discharge. In addition, long-term potential for harm (microchimerism) is not known.

“There was a consistent nonsignificant acute benefit for liberal transfusion and a nominal reduction in CV mortality and improved outcomes in patients with type 1 MI in exploratory analyses, in a trial that ended up underpowered,” Dr. Gibson summarized. “Long-term follow up would be helpful to evaluate chronic outcomes.”

This is a very well-conducted, high-quality, important study that will be considered a landmark trial, C. David Mazer, MD, University of Toronto and St. Michael’s Hospital, also in Toronto, said in an interview.

Unfortunately, “it was not as definitive as hoped for,” Dr. Mazer lamented. Nevertheless, “I think people may interpret it as providing support for a liberal transfusion strategy” in patients with anemia and MI, he said.

Dr. Mazer, who was not involved with this research, was a principal investigator on the TRICS-3 trial, which disputed a liberal RBC transfusion strategy in patients with anemia undergoing cardiac surgery, as previously reported.

The “Red Blood Cell Transfusion: 2023 AABB International Guidelines,” led by Dr. Carson and published in JAMA, recommend a restrictive strategy in stable patients, although these guidelines did not include the current study, Dr. Mazer observed.

In the REALITY trial, there were fewer major adverse cardiac events (MACE) events in the restrictive strategy, he noted.

MINT can be viewed as comparing a high versus low hemoglobin threshold. “It is possible that the best is in between,” he said.

Dr. Mazer also noted that MINT may have achieved significance if it was designed with a larger enrollment and a higher power (for example, 90% instead of 80%) to detect between-group difference for the primary outcome. 
 

Study rationale, design, and findings

Anemia, or low RBC count, is common in patients with MI, Dr. Carson noted. A normal hemoglobin is 13 g/dL in men and 12 g/dL in women. Administering a packed RBC transfusion only when a patient’s hemoglobin falls below 7 or 8 g/dL has been widely adopted, but it is unclear if patients with acute MI may benefit from a higher hemoglobin level.

“Blood transfusion may decrease ischemic injury by improving oxygen delivery to myocardial tissues and reduce the risk of reinfarction or death,” the researchers wrote. “Alternatively, administering more blood could result in more frequent heart failure from fluid overload, infection from immunosuppression, thrombosis from higher viscosity, and inflammation.”

From 2017 to 2023, investigators enrolled 3,504 adults aged 18 and older at 144 sites in the United States (2,157 patients), Canada (885), France (323), Brazil (105), New Zealand (25), and Australia (9).

The participants had ST-elevation or non–ST-elevation MI and hemoglobin less than 10 g/dL within 24 hours. Patients with type 1 (atherosclerotic plaque disruption), type 2 (supply-demand mismatch without atherothrombotic plaque disruption), type 4b, or type 4c MI were eligible.

They were randomly assigned to receive:

• A ‘restrictive’ transfusion strategy (1,749 patients): Transfusion was permitted but not required when a patient’s hemoglobin was less than 8 g/dL and was strongly recommended when it was less than 7 g/dL or when anginal symptoms were not controlled with medications.
• A ‘liberal’ transfusion strategy (1,755 patients): One unit of RBCs was administered after randomization, and RBCs were transfused to maintain hemoglobin 10 g/dL or higher until hospital discharge or 30 days. 

The patients had a mean age of 72 years and 46% were women. More than three-quarters (78%) were White and 14% were Black. They had frequent coexisting illnesses, about a third had a history of MI, percutaneous coronary intervention, or heart failure; 14% were on a ventilator and 12% had renal dialysis. The median duration of hospitalization was 5 days in the two groups.

At baseline, the mean hemoglobin was 8.6 g/dL in both groups. At days 1, 2, and 3, the mean hemoglobin was 8.8, 8.9, and 8.9 g/dL, respectively, in the restrictive transfusion group, and 10.1, 10.4, and 10.5 g/dL, respectively, in the liberal transfusion group.

The mean number of transfused blood units was 0.7 units in the restrictive strategy group and 2.5 units in the liberal strategy group, roughly a 3.5-fold difference.

After adjustment for site and incomplete follow-up in 57 patients (20 with the restrictive strategy and 37 with the liberal strategy), the estimated RR for the primary outcome in the restrictive group versus the liberal group was 1.15 (P = .07).

A version of this article first appeared on Medscape.com.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Dermatopathologists tend to render “more severe diagnoses for skin biopsy cases of melanocytic lesions” more often than general pathologists, results from an exploratory study showed.

The findings “could in part play a role in the rising incidence of early-stage melanoma with low risk of progression or patient morbidity, thereby contributing to increasing rates of overdiagnosis,” researchers led by co–senior authors Joann G. Elmore, MD, MPH, of the University of California, Los Angeles, and Raymond L. Barnhill, MD, MBA, of the Institut Curie, Paris, wrote in their study, published online in JAMA Dermatology.

To investigate the characteristics associated with rendering higher-grade diagnoses, including invasive melanoma, the researchers drew from two national data sets: the Melanoma Pathology (M-Path) study, conducted from July 2013 to May 2016, and the Reducing Errors in Melanocytic Interpretations (REMI) study, conducted from August 2018 to March 2021. In both studies, pathologists who interpreted melanocytic lesions in their clinical practices interpreted study cases in glass slide format. For the current study, researchers used logistic regression to examine the association of pathologist characteristics with diagnosis of a study case as higher grade (including severely dysplastic and melanoma in situ) vs. lower grade (including mild to moderately dysplastic nevi) and diagnosis of invasive melanoma vs. any less severe diagnosis.

A total of 338 pathologists were included in the analysis. Of these, 113 were general pathologists and 225 were dermatopathologists (those who were board certified and/or fellowship trained in dermatopathology).

The researchers found that, compared with general pathologists, dermatopathologists were 2.63 times more likely to render higher-grade diagnoses and 1.95 times more likely to diagnose invasive melanoma (P < .001 for both associations). Diagnoses of stage pT1a melanomas with no mitotic activity completely accounted for the difference between dermatopathologists and general pathologists in diagnosing invasive melanoma.

For the analysis limited to the 225 dermatopathologists, those with a higher practice caseload of melanocytic lesions were more likely to assign higher-grade diagnoses (odds ratio for trend, 1.27; P = .02), while those affiliated with an academic center had lower odds of diagnosing invasive melanoma (OR, 0.61; P = .049).

The researchers acknowledged limitations of their analysis, including the lack of data on patient outcomes, “so we could not make conclusions about the clinical outcome of any particular diagnosis by a study participant,” they wrote. “While our analyses revealed pathologist characteristics associated with assigning more vs. less severe diagnoses of melanocytic lesions, we could not conclude that any particular diagnosis by a study participant was overcalling or undercalling. However, the epidemiologic evidence that melanoma is overdiagnosed suggests that overcalling by some pathologists may be contributing to increasing rates of low-risk melanoma diagnoses.”

In an accompanying editorial, authors Klaus J. Busam, MD, of the department of pathology and laboratory medicine at Memorial Sloan Kettering Cancer Center, New York, Pedram Gerami, MD, of the department of dermatology at Northwestern University, Chicago, and Richard A. Scolyer, MD, of the Melanoma Institute, Wollstonecraft, Australia, wrote that the study findings “raise the question of whether subspecialization in dermatopathology may be a factor contributing to the epidemiologic phenomenon of overdiagnosis – that is, the discordance in the rise of melanoma incidence and relatively constant annual mortality rates over many decades. The findings also invite a discussion about strategies to minimize harm from overdiagnosis for both patients and the health care system.”

To minimize misdiagnoses, they continued, efforts to facilitate diagnostic accuracy should be encouraged. “Excisional (rather than partial) biopsies and provision of relevant clinical information would facilitate rendering of the correct histopathologic diagnosis,” they wrote. “When the diagnosis is uncertain, this is best acknowledged. If felt necessary, a reexcision of a lesion with an uncertain diagnosis can be recommended without upgrading the diagnosis.”

In addition, “improvements in prognosis are needed beyond American Joint Committee on Cancer staging,” they noted. “This will likely require a multimodal approach with novel methods, including artificial intelligence and biomarkers that help distinguish low-risk melanomas, for which a conservative approach may be appropriate, from those that require surgical intervention.”

The study was supported by the National Center for Advancing Translational Sciences and by the National Institutes of Health. One author disclosed receiving grants from the National Cancer Institute during the conduct of the study, and another disclosed serving as editor in chief of Primary Care topics at UpToDate; other authors had no disclosures. Dr. Busam reported receiving nonfinancial support from the American Society of Dermatopathology. Dr. Gerami reported receiving consulting fees from Castle Biosciences. Dr. Scolyer reported receiving an investigator grant from the National Health and Medical Research Council of Australia during the conduct of the study and personal fees from several pharmaceutical companies outside the submitted work.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.

Patients with immune-mediated diseases and a history of malignancy had similar rates of cancer recurrence whether or not they were receiving immunosuppressive treatments, shows a newly published systematic review and meta-analysis that covered approximately 24,000 patients and 86,000 person-years of follow-up.

The findings could “help guide clinical decision making,” providing “reassurance that it remains safe to use conventional immunomodulators, anti-TNF [tumor necrosis factor] agents, or newer biologics in individuals with [immune-mediated diseases] with a prior malignancy consistent with recent guidelines,” Akshita Gupta, MD, of Massachusetts General Hospital, Boston, and coinvestigators wrote in Clinical Gastroenterology and Hepatology.

And because a stratification of studies by the timing of immunosuppression therapy initiation found no increased risk when treatment was started within 5 years of a cancer diagnosis compared to later on, the meta-analysis could “potentially reduce the time to initiation of immunosuppressive treatment,” the authors wrote, noting a continued need for individualized decision-making.

Ustekinumab, a monoclonal antibody targeting interleukin-12 and IL-23, and vedolizumab, a monoclonal antibody that binds to alpha4beta₇ integrin, were covered in the meta-analysis, but investigators found no studies on the use of upadacitinib or other Janus kinase (JAK) inhibitors, or the use of S1P modulators, in patients with prior malignancies.

The analysis included 31 observational studies, 17 of which involved patients with inflammatory bowel disease (IBD). (Of the other studies, 14 involved patients with rheumatoid arthritis, 2 covered psoriasis, and 1 covered ankylosing spondylitis.)
 

Similar levels of risk

The incidence rate of new or recurrent cancers among individuals not receiving any immunosuppressive therapy for IBD or other immune-mediated diseases after an index cancer was 35 per 1,000 patient-years (95% confidence interval, 27-43 per 1,000 patient-years; 1,627 incident cancers among 12,238 patients, 43,765 patient-years), and the rate among anti-TNF users was similar at 32 per 1,000 patient-years (95% CI, 25-38 per 1,000 patient-years; 571 cancers among 3,939 patients, 17,772 patient-years).

Among patients on conventional immunomodulator therapy (thiopurines, methotrexate), the incidence rate was numerically higher at 46 per 1,000 patient-years (95% CI, 31-61; 1,104 incident cancers among 5,930 patients; 17,018 patient-years), but was not statistically different from anti-TNF (P = .92) or no immunosuppression (P = .98).

Patients on combination immunosuppression also had numerically higher rates of new or recurrent cancers at 56 per 1,000 patient-years (95% CI, 31-81; 179 incident cancers, 2,659 patient-years), but these rates were not statistically different from immunomodulator use alone (P = .19), anti-TNF alone (P = .06) or no immunosuppressive therapy (P = .14).

Patients on ustekinumab and vedolizumab similarly had numerically lower rates of cancer recurrence, compared with other treatment groups: 21 per 1,000 patient-years (95% CI, 0-44; 5 cancers among 41 patients, 213 patient-years) and 16 per 1,000 patient-years (95% CI, 5-26; 37 cancers among 281 patients, 1,951 patient-years). However, the difference was statistically significant only for vedolizumab (P = .03 vs. immunomodulators and P = .04 vs. anti-TNF agents).

Subgroup analyses for new primary cancers, recurrence of a prior cancer, and type of index cancer (skin cancer vs. other cancers) similarly found no statistically significant differences between treatment arms. Results were similar in patients with IBD and RA.
 

Timing of therapy

The new meta-analysis confirms and expands a previous meta-analysis published in Gastroenterology in 2016 that showed no impact of treatment – primarily IMM or anti-TNF treatment – on cancer recurrence in patients with immune-mediated diseases, Dr. Gupta and coauthors wrote.

The 2016 meta-analysis reported similar cancer recurrence rates with IMMs and anti-TNFs when immunosuppression was introduced before or after 6 years of cancer diagnosis. In the new meta-analysis – with twice the number of patients, a longer duration of follow-up, and the inclusion of other biologic therapies – a stratification of results at the median interval of therapy initiation similarly found no increased risk before 5 years, compared with after 5 years.

“Although several existing guidelines recommend avoiding immunosuppression for 5 years after the index cancer, our results indicate that it may be safe to initiate these agents earlier than 5 years, at least in some patients,” Dr. Gupta and coauthors wrote, mentioning the possible impact of selection bias and surveillance bias in the study. Ongoing registries “may help answer this question more definitively with prospectively collected data, but inherently may suffer from this selection bias as well.”

Assessment of the newer biologics ustekinumab and vedolizumab is limited by the low number of studies (four and five, respectively) and by limited duration of follow-up. “Longer-term evaluation after these treatments is essential but it is reassuring that in the early analysis we did not observe an increase and in fact noted numerically lower rates of cancers,” they wrote.

It is also “critically important” to generate more data on JAK inhibitors, and to further study the safety of combining systemic chemotherapy and the continuation of IBD therapy in the setting of a new cancer diagnosis, they wrote.

The study was funded in part by grants from the Crohn’s and Colitis Foundation, and the Chleck Family Foundation. Dr. Gupta disclosed no conflicts. One coauthor disclosed consulting for Abbvie, Amgen, Biogen, and other companies, and receiving grants from several companies. Another coauthor disclosed serving on the scientific advisory boards for AbbVie and other companies, and receiving research support from Pfizer.