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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
Frailty screening should be routine in endometrial cancer surgery
Endometrial cancer patients should be screened for frailty before hysterectomies, and frail patients should be counseled thoroughly about their increased risk for poor outcomes, according to a review of 144,809 cases in the Nationwide Readmissions Database.
Overall, 1.8% of the women were frail according to the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, which characterizes patients as frail or not based on diagnostic codes in a range of areas, including abnormal weight loss, dementia, urinary or fecal incontinence, difficulty walking, inadequate social support, and other matters.
Frailty was associated with an almost fourfold increased risk of intensive care after surgery; a more than twofold risk of inpatient mortality, and a 59% increased risk of something other than routine discharge to home. Frail patients were 33% more likely to be readmitted within 30 days and 21% more likely to be readmitted within 90 days, and they had a higher risk of dying on readmission. Hospital costs and lengths of stay were higher for frail women, according to the report, which was published online in Gynecologic Oncology.
The findings were adjusted for patient, hospital, and clinical factors, and the readmission outcomes were unchanged when limited to patients who had minimally invasive surgery.
Frailty is a well-known risk factor for poor surgical outcomes, so it “comes as little surprise” that it was associated with worse outcomes in hysterectomies for endometrial cancer. Even so, “frailty is oftentimes not screened for in oncology clinics” leading to “a large number of potentially unrecognized frail patients who are recommended to undergo surgery,” said investigators led by Tiffany Sia, MD, an obstetrics and gynecology resident at Columbia University, New York.
“We believe that each potential patient’s frailty status should be assessed during the preoperative period ... frail patients should be counseled regarding these risks in the perioperative setting,” Dr. Sia said in an interview.
“Researchers and clinicians have adopted the scoring instrument that corresponds best with the data they have available,” but “lack of a widely recognized gold standard or easily utilized diagnostic tool makes frailty rather difficult to formally assess in a clinical setting,” she said.
The investigators found a “surprisingly high rate” of frail patients (82%) who underwent total abdominal hysterectomies compared to less invasive options, with 16.5% undergoing extended procedures. The reason is unknown because stage, tumor grade, and histology – factors that likely influenced decision making – were not captured in the analysis.
However, almost half of the frail subjects were 70 years or older, and increasing age is associated with more aggressive tumor characteristics and worse prognosis.
The team said future research should integrate screening instruments into routine clinic workflow, but there have been a number of roadblocks. Current screening instruments are “cumbersome to use and difficult to implement ... as they typically require measurement of a frailty phenotype such as a timed up-and-go test or grip strength and require numerous patient surveys,” they added.
Proposed screening tools include the Frailty Index, Memorial Sloan Kettering–Frailty Index, Hopkins’ frailty indicator, and the Vulnerable Elders Survey, but no preferred method has emerged, and each scale captures different subpopulations of frailty and differs in its prognostic ability.
There was no external funding, and Dr. Sia didn’t have any disclosures.
Endometrial cancer patients should be screened for frailty before hysterectomies, and frail patients should be counseled thoroughly about their increased risk for poor outcomes, according to a review of 144,809 cases in the Nationwide Readmissions Database.
Overall, 1.8% of the women were frail according to the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, which characterizes patients as frail or not based on diagnostic codes in a range of areas, including abnormal weight loss, dementia, urinary or fecal incontinence, difficulty walking, inadequate social support, and other matters.
Frailty was associated with an almost fourfold increased risk of intensive care after surgery; a more than twofold risk of inpatient mortality, and a 59% increased risk of something other than routine discharge to home. Frail patients were 33% more likely to be readmitted within 30 days and 21% more likely to be readmitted within 90 days, and they had a higher risk of dying on readmission. Hospital costs and lengths of stay were higher for frail women, according to the report, which was published online in Gynecologic Oncology.
The findings were adjusted for patient, hospital, and clinical factors, and the readmission outcomes were unchanged when limited to patients who had minimally invasive surgery.
Frailty is a well-known risk factor for poor surgical outcomes, so it “comes as little surprise” that it was associated with worse outcomes in hysterectomies for endometrial cancer. Even so, “frailty is oftentimes not screened for in oncology clinics” leading to “a large number of potentially unrecognized frail patients who are recommended to undergo surgery,” said investigators led by Tiffany Sia, MD, an obstetrics and gynecology resident at Columbia University, New York.
“We believe that each potential patient’s frailty status should be assessed during the preoperative period ... frail patients should be counseled regarding these risks in the perioperative setting,” Dr. Sia said in an interview.
“Researchers and clinicians have adopted the scoring instrument that corresponds best with the data they have available,” but “lack of a widely recognized gold standard or easily utilized diagnostic tool makes frailty rather difficult to formally assess in a clinical setting,” she said.
The investigators found a “surprisingly high rate” of frail patients (82%) who underwent total abdominal hysterectomies compared to less invasive options, with 16.5% undergoing extended procedures. The reason is unknown because stage, tumor grade, and histology – factors that likely influenced decision making – were not captured in the analysis.
However, almost half of the frail subjects were 70 years or older, and increasing age is associated with more aggressive tumor characteristics and worse prognosis.
The team said future research should integrate screening instruments into routine clinic workflow, but there have been a number of roadblocks. Current screening instruments are “cumbersome to use and difficult to implement ... as they typically require measurement of a frailty phenotype such as a timed up-and-go test or grip strength and require numerous patient surveys,” they added.
Proposed screening tools include the Frailty Index, Memorial Sloan Kettering–Frailty Index, Hopkins’ frailty indicator, and the Vulnerable Elders Survey, but no preferred method has emerged, and each scale captures different subpopulations of frailty and differs in its prognostic ability.
There was no external funding, and Dr. Sia didn’t have any disclosures.
Endometrial cancer patients should be screened for frailty before hysterectomies, and frail patients should be counseled thoroughly about their increased risk for poor outcomes, according to a review of 144,809 cases in the Nationwide Readmissions Database.
Overall, 1.8% of the women were frail according to the Johns Hopkins Adjusted Clinical Groups (ACG) frailty indicator, which characterizes patients as frail or not based on diagnostic codes in a range of areas, including abnormal weight loss, dementia, urinary or fecal incontinence, difficulty walking, inadequate social support, and other matters.
Frailty was associated with an almost fourfold increased risk of intensive care after surgery; a more than twofold risk of inpatient mortality, and a 59% increased risk of something other than routine discharge to home. Frail patients were 33% more likely to be readmitted within 30 days and 21% more likely to be readmitted within 90 days, and they had a higher risk of dying on readmission. Hospital costs and lengths of stay were higher for frail women, according to the report, which was published online in Gynecologic Oncology.
The findings were adjusted for patient, hospital, and clinical factors, and the readmission outcomes were unchanged when limited to patients who had minimally invasive surgery.
Frailty is a well-known risk factor for poor surgical outcomes, so it “comes as little surprise” that it was associated with worse outcomes in hysterectomies for endometrial cancer. Even so, “frailty is oftentimes not screened for in oncology clinics” leading to “a large number of potentially unrecognized frail patients who are recommended to undergo surgery,” said investigators led by Tiffany Sia, MD, an obstetrics and gynecology resident at Columbia University, New York.
“We believe that each potential patient’s frailty status should be assessed during the preoperative period ... frail patients should be counseled regarding these risks in the perioperative setting,” Dr. Sia said in an interview.
“Researchers and clinicians have adopted the scoring instrument that corresponds best with the data they have available,” but “lack of a widely recognized gold standard or easily utilized diagnostic tool makes frailty rather difficult to formally assess in a clinical setting,” she said.
The investigators found a “surprisingly high rate” of frail patients (82%) who underwent total abdominal hysterectomies compared to less invasive options, with 16.5% undergoing extended procedures. The reason is unknown because stage, tumor grade, and histology – factors that likely influenced decision making – were not captured in the analysis.
However, almost half of the frail subjects were 70 years or older, and increasing age is associated with more aggressive tumor characteristics and worse prognosis.
The team said future research should integrate screening instruments into routine clinic workflow, but there have been a number of roadblocks. Current screening instruments are “cumbersome to use and difficult to implement ... as they typically require measurement of a frailty phenotype such as a timed up-and-go test or grip strength and require numerous patient surveys,” they added.
Proposed screening tools include the Frailty Index, Memorial Sloan Kettering–Frailty Index, Hopkins’ frailty indicator, and the Vulnerable Elders Survey, but no preferred method has emerged, and each scale captures different subpopulations of frailty and differs in its prognostic ability.
There was no external funding, and Dr. Sia didn’t have any disclosures.
FROM GYNECOLOGIC ONCOLOGY
Upfront asymptomatic primary tumor resection: No benefit in advanced CRC
Upfront resection of an asymptomatic primary tumor does not improve survival over chemotherapy alone in stage IV colorectal cancer with unresectable synchronous metastases, according to a randomized trial in Japan with 165 patients.
Median overall survival was slightly more than 2 years with or without primary resection, plus upfront surgery delayed systemic treatment and had a 4% risk of fatal complications. The trial was terminated early because of futility.
“PTR [primary tumor resection] should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” said investigators led by Yukihide Kanemitsu, MD, a colorectal surgeon at National Cancer Center Hospital in Tokyo.
“This paper is important for establishing solid evidence-based decisions. Why perform an invasive procedure on a patient that introduces additional risks if it won’t change their disease course?” said colorectal surgeon Deborah Keller, MD, clinical assistant professor of surgery at the University of California at Davis Medical Center, when asked for comment.
She explained that, in general, when the primary tumor is not obstructing, the standard of care is upfront chemotherapy, as supported by National Comprehensive Cancer Network guidelines.
“However, there was a change in practice over the last few years” after several retrospective studies reported better overall survival with surgery before chemotherapy, but “the studies were not the highest quality of evidence,” she said.
To bring better data to bear, the Japanese team randomized 84 patients to chemotherapy alone and 81 to PTR followed by chemotherapy. Primary tumors were asymptomatic, and patients had no more than three unresectable metastases in the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy was either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab at investigator discretion.
The trial was halted at interim analysis in September 2019. With a median follow-up of 22 months, median overall survival – the primary endpoint – was 25.9 months in the surgery-first arm and 26.7 months in the chemotherapy-alone group (P = .69). Subgroup analysis found no populations that benefited from PTR. Median progression free survival was 10.4 months with PTR first and 12.1 months with chemotherapy alone (P = .48)
Twenty-seven patients in the PTR arm had grade 3 or worse surgery-related adverse events, including anastomotic leakage in 3 and increased aspartate aminotransferase in 13. Three patients (4%) died within 30 days of surgery. Chemotherapy-related grade 3 or worse adverse events were more frequent and severe in the PTR arm (48% PTR versus 34% chemotherapy alone).
“For those who had been performing resections, this could push the paradigm back to chemotherapy alone,” Dr. Keller said.
Eleven patients (13%) in the chemotherapy-alone arm required surgery for intestinal obstruction or other primary tumor symptoms that developed after randomization, which means that 87% avoided surgery entirely, the investigators noted.
In the PTR group, surgery was performed within 21 days of enrollment, and chemotherapy started a median of 34 days after PTR. Chemotherapy was started within 14 days of enrollment in the chemotherapy-alone arm.
The groups were well balanced, including colon and rectosigmoid tumor locations in 93% of both arms and liver metastases in 73% of both. A bit over half the subjects were men and the median age was 65 years.
The team noted that early termination meant that the planned sample size was not achieved, which in turn limited the statistical power of the conclusions. “It is hoped that the comprehensive results of [ongoing trials] will clearly demonstrate the role of PTR for these patients,” they said.
The study was conducted by the Japan Clinical Oncology Group at 38 cancer centers in Japan. The work was funded by the Ministry of Health of Japan. The investigators had numerous industry ties, including Dr. Kanemitsu, who reported honoraria from Chugai Pharma, Ethicon, Covidien, and Intuitive Surgical, and being a Covidien adviser.
Upfront resection of an asymptomatic primary tumor does not improve survival over chemotherapy alone in stage IV colorectal cancer with unresectable synchronous metastases, according to a randomized trial in Japan with 165 patients.
Median overall survival was slightly more than 2 years with or without primary resection, plus upfront surgery delayed systemic treatment and had a 4% risk of fatal complications. The trial was terminated early because of futility.
“PTR [primary tumor resection] should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” said investigators led by Yukihide Kanemitsu, MD, a colorectal surgeon at National Cancer Center Hospital in Tokyo.
“This paper is important for establishing solid evidence-based decisions. Why perform an invasive procedure on a patient that introduces additional risks if it won’t change their disease course?” said colorectal surgeon Deborah Keller, MD, clinical assistant professor of surgery at the University of California at Davis Medical Center, when asked for comment.
She explained that, in general, when the primary tumor is not obstructing, the standard of care is upfront chemotherapy, as supported by National Comprehensive Cancer Network guidelines.
“However, there was a change in practice over the last few years” after several retrospective studies reported better overall survival with surgery before chemotherapy, but “the studies were not the highest quality of evidence,” she said.
To bring better data to bear, the Japanese team randomized 84 patients to chemotherapy alone and 81 to PTR followed by chemotherapy. Primary tumors were asymptomatic, and patients had no more than three unresectable metastases in the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy was either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab at investigator discretion.
The trial was halted at interim analysis in September 2019. With a median follow-up of 22 months, median overall survival – the primary endpoint – was 25.9 months in the surgery-first arm and 26.7 months in the chemotherapy-alone group (P = .69). Subgroup analysis found no populations that benefited from PTR. Median progression free survival was 10.4 months with PTR first and 12.1 months with chemotherapy alone (P = .48)
Twenty-seven patients in the PTR arm had grade 3 or worse surgery-related adverse events, including anastomotic leakage in 3 and increased aspartate aminotransferase in 13. Three patients (4%) died within 30 days of surgery. Chemotherapy-related grade 3 or worse adverse events were more frequent and severe in the PTR arm (48% PTR versus 34% chemotherapy alone).
“For those who had been performing resections, this could push the paradigm back to chemotherapy alone,” Dr. Keller said.
Eleven patients (13%) in the chemotherapy-alone arm required surgery for intestinal obstruction or other primary tumor symptoms that developed after randomization, which means that 87% avoided surgery entirely, the investigators noted.
In the PTR group, surgery was performed within 21 days of enrollment, and chemotherapy started a median of 34 days after PTR. Chemotherapy was started within 14 days of enrollment in the chemotherapy-alone arm.
The groups were well balanced, including colon and rectosigmoid tumor locations in 93% of both arms and liver metastases in 73% of both. A bit over half the subjects were men and the median age was 65 years.
The team noted that early termination meant that the planned sample size was not achieved, which in turn limited the statistical power of the conclusions. “It is hoped that the comprehensive results of [ongoing trials] will clearly demonstrate the role of PTR for these patients,” they said.
The study was conducted by the Japan Clinical Oncology Group at 38 cancer centers in Japan. The work was funded by the Ministry of Health of Japan. The investigators had numerous industry ties, including Dr. Kanemitsu, who reported honoraria from Chugai Pharma, Ethicon, Covidien, and Intuitive Surgical, and being a Covidien adviser.
Upfront resection of an asymptomatic primary tumor does not improve survival over chemotherapy alone in stage IV colorectal cancer with unresectable synchronous metastases, according to a randomized trial in Japan with 165 patients.
Median overall survival was slightly more than 2 years with or without primary resection, plus upfront surgery delayed systemic treatment and had a 4% risk of fatal complications. The trial was terminated early because of futility.
“PTR [primary tumor resection] should no longer be considered a standard of care for patients with CRC with asymptomatic primary tumors and synchronous unresectable metastases,” said investigators led by Yukihide Kanemitsu, MD, a colorectal surgeon at National Cancer Center Hospital in Tokyo.
“This paper is important for establishing solid evidence-based decisions. Why perform an invasive procedure on a patient that introduces additional risks if it won’t change their disease course?” said colorectal surgeon Deborah Keller, MD, clinical assistant professor of surgery at the University of California at Davis Medical Center, when asked for comment.
She explained that, in general, when the primary tumor is not obstructing, the standard of care is upfront chemotherapy, as supported by National Comprehensive Cancer Network guidelines.
“However, there was a change in practice over the last few years” after several retrospective studies reported better overall survival with surgery before chemotherapy, but “the studies were not the highest quality of evidence,” she said.
To bring better data to bear, the Japanese team randomized 84 patients to chemotherapy alone and 81 to PTR followed by chemotherapy. Primary tumors were asymptomatic, and patients had no more than three unresectable metastases in the liver, lungs, distant lymph nodes, or peritoneum. Chemotherapy was either mFOLFOX6 plus bevacizumab or CapeOX plus bevacizumab at investigator discretion.
The trial was halted at interim analysis in September 2019. With a median follow-up of 22 months, median overall survival – the primary endpoint – was 25.9 months in the surgery-first arm and 26.7 months in the chemotherapy-alone group (P = .69). Subgroup analysis found no populations that benefited from PTR. Median progression free survival was 10.4 months with PTR first and 12.1 months with chemotherapy alone (P = .48)
Twenty-seven patients in the PTR arm had grade 3 or worse surgery-related adverse events, including anastomotic leakage in 3 and increased aspartate aminotransferase in 13. Three patients (4%) died within 30 days of surgery. Chemotherapy-related grade 3 or worse adverse events were more frequent and severe in the PTR arm (48% PTR versus 34% chemotherapy alone).
“For those who had been performing resections, this could push the paradigm back to chemotherapy alone,” Dr. Keller said.
Eleven patients (13%) in the chemotherapy-alone arm required surgery for intestinal obstruction or other primary tumor symptoms that developed after randomization, which means that 87% avoided surgery entirely, the investigators noted.
In the PTR group, surgery was performed within 21 days of enrollment, and chemotherapy started a median of 34 days after PTR. Chemotherapy was started within 14 days of enrollment in the chemotherapy-alone arm.
The groups were well balanced, including colon and rectosigmoid tumor locations in 93% of both arms and liver metastases in 73% of both. A bit over half the subjects were men and the median age was 65 years.
The team noted that early termination meant that the planned sample size was not achieved, which in turn limited the statistical power of the conclusions. “It is hoped that the comprehensive results of [ongoing trials] will clearly demonstrate the role of PTR for these patients,” they said.
The study was conducted by the Japan Clinical Oncology Group at 38 cancer centers in Japan. The work was funded by the Ministry of Health of Japan. The investigators had numerous industry ties, including Dr. Kanemitsu, who reported honoraria from Chugai Pharma, Ethicon, Covidien, and Intuitive Surgical, and being a Covidien adviser.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Study supports lower starting dose of lenvatinib for endometrial cancer
The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.
“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.
Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).
This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.
Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.
“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
Study rationale
Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.
However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.
MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.
“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.
The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
Results and implications
Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.
In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.
There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).
However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).
The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.
Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).
There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.
The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).
Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.
In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.
“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”
This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.
The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.
“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.
Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).
This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.
Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.
“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
Study rationale
Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.
However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.
MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.
“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.
The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
Results and implications
Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.
In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.
There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).
However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).
The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.
Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).
There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.
The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).
Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.
In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.
“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”
This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.
The study included 70 patients who received lenvatinib in combination with pembrolizumab. Patients who were started on 14 mg of lenvatinib per day had fewer dose reductions and a longer time to the first dose reduction, compared with patients who were started on the recommended 20-mg dose. There were no significant differences in response, progression-free survival, or overall survival between the two dose groups.
“Published studies and these results may support using lenvatinib at a starting dose of 14 mg daily in clinical practice,” said Jeffrey How, MD, a gynecologic oncology fellow at MD Anderson Cancer Center in Houston.
Dr. How presented the results at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10775).
This is not the first time a recommended starting dose has been deemed too high to use in practice, according to Carol Aghajanian, MD, chief of gynecologic medical oncology at Memorial Sloan Kettering Cancer Center in New York and a panelist for the session where Dr. How presented his research.
Dr. Aghajanian noted that pegylated liposomal doxorubicin and topotecan are “rarely, if ever” started at the labeling doses for recurrent ovarian cancer. Those doses proved to be too high for general practice and “not tolerable with multicycle treatment,” she said.
“We may again be experiencing the effect of single-cycle, dose-limiting toxicity information not guiding us well in how to treat patients over time,” she added.
Study rationale
Based on a 38% overall response rate in the phase 2 KEYNOTE-146 trial, lenvatinib plus pembrolizumab was approved in September 2019 to treat patients with advanced endometrial carcinoma that is not microsatellite instability–high or mismatch repair deficient who have progressed on systemic therapy and are not candidates for curative surgery or radiation.
However, the rate of grade 3/4 adverse events with the combination was 66.9% in the trial, leading to dose interruptions or reductions and a discontinuation rate of 17.7%.
MD Anderson oncologists noticed similar toxicity rates at the approved lenvatinib dose of 20 mg per day when they started using the combination in October 2019. It raised a question about the feasibility of implementing the regimen in general practice as well as concerns about compliance, Dr. How said.
“As a consequence, our team started patients on a reduced dose of lenvatinib to improve safety and tolerability,” he added.
The mean dose intensity in the phase 2 trial was 14.4 mg/day, so the team began to start patients on 14 mg daily.
Results and implications
Of the 70 patients studied, 16 were started at 20 mg, and 54 were started at 14 mg. There were no significant differences between the two groups at baseline.
In the entire cohort, the median age was 65.5 years, and patients had received a median of two prior lines of therapy (range, one to nine). Most patients (90%) had a performance status of 0 or 1, 92.9% had microsatellite stable tumors, and 27.1% each had endometrioid or serous histology.
There was no significant difference between the dose groups with regard to any hospitalization (P = .46), hospitalization due to treatment-related adverse events (P = .55), dose interruption (P = .18), or treatment discontinuation due to treatment-related adverse events (P = .54).
However, the average number of dose reductions per patient was higher in the 20-mg group than in the 14-mg group – 1.1 and 0.4, respectively (P = .003).
The increased dose reductions with the higher starting dose were due mostly to gastrointestinal and hematologic adverse events as well as fatigue and anorexia, all of which were far more common in patients started at 20 mg.
Patients in the 14-mg group had a longer time to the first dose reduction or discontinuation due to toxicity – 107 days vs. 42 days in the 20-mg group (P = .001).
There was no significant difference in response rates between the 14-mg and 20-mg groups – 38.2% and 28.6%, respectively (P = .51) – and no significant difference in clinical benefit rates – 72.3% and 57.1%, respectively.
The median progression-free survival was 3.2 months in the 20-mg group and 5.5 months in the 14-mg group (P = .25). The median overall survival was 8.6 months and 10.3 months, respectively (P = .95).
Dr. How noted that this study was limited by its retrospective nature, and the small number of women started at 20 mg may have limited the ability to detect differences with a lower starting dose. Still, these results seem to support a starting dose of 14 mg, he concluded.
In a discussion after Dr. How’s presentation, panelist Judith Smith, PharmD, of UT Health in Houston, noted that her practice is starting women on lenvatinib at 12 mg per day.
“You can use the 14-mg convenience pack, but, from a cost perspective ... we have to be cognizant of the financial toxicity,” she said. “[Combining the] 10-mg and 4-mg tablets is going to be more expensive, so we’ve been using the 4-mg tablets [three per day] and starting at 12 mg.”
This study was funded by MD Anderson and the National Institutes of Health. Dr. How reported having no conflicts of interest. Dr. Aghajanian and Dr. Smith did not provide disclosures.
FROM SGO 2021
Cytoreduction in advanced ovarian cancer: ‘Keep the status quo’
A retrospective, case-control study showed that optimal cytoreductive surgery is an independent predictor of overall survival, even when controlling for response to chemotherapy.
The findings were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10243).
Response to platinum-based chemotherapy is the strongest predictor of overall survival in advanced ovarian cancer, noted Nicholas Cardillo, MD, a gynecologic oncology fellow at the University of Iowa, Iowa City, who presented the findings at the meeting.
In recent years, a poor response to chemotherapy has sometimes been used as justification to forgo cytoreduction, Dr. Cardillo added.
He and his colleagues looked into this issue because evidence to support the practice is lacking. With their study, the researchers found that optimal cytoreduction – removing all disease of 1 cm or more – improved survival regardless of the response to chemotherapy.
“My advice right now is that debulking surgery should still be attempted in all patients with ovarian cancer because, as far as we know right now, optimal cytoreduction will improve survival,” Dr. Cardillo said in an interview. “Basically, this study argues to keep the status quo, which is to perform surgery.”
The status quo might change with future research, Dr. Cardillo acknowledged, “but as of right now, we have no evidence to support not pursuing cytoreduction in these patients.”
Study details and results
The researchers analyzed data on 234 patients who responded to platinum-based chemotherapy – meaning they had no evidence of disease for at least 6 months afterward – and 98 patients who did not respond – meaning they progressed during therapy, had stable disease, did not respond completely, or had a progression-free survival duration of less than 6 months. Subjects had stage III or IV high-grade serous ovarian cancer.
About three-quarters of responders and 57% of nonresponders had optimal surgery. Only seven patients in each group had fewer than six cycles of chemotherapy.
The mean age was 59 years in the responder group and 62 years among nonresponders. Stage IV disease, including upper-abdominal and chest involvement, was more common in the nonresponder group.
The median overall survival was 44.8 months in the responder group and 18.1 months among nonresponders (P < .001). The median overall survival was 34.2 months among patients who underwent optimal surgery and 24.8 months among those who did not (P < .001).
Predictors of survival
A multivariate analysis showed that response to chemotherapy had the greatest effect on survival, with a hazard ratio of 0.27 (P < .001).
“The second most significant predictor of overall survival was receipt of neoadjuvant chemotherapy [HR, 2.84; P < .001], which is intuitive as that is typically a marker for worse disease burden,” Dr. Cardillo said.
“But most importantly for our question is that optimal surgery is an independent significant factor in overall survival, even when controlling for other significant risk factors, including whether or not a patient responds to chemotherapy. The hazard ratio is 0.73 [P = .023], indicating a 25%-30% improvement in overall survival,” he added.
Based on these results, “surgical debulking should still be considered a component of the treatment algorithm in ovarian cancer patients who have a poor response to chemotherapy, if an optimal surgery is deemed feasible,” Dr. Cardillo concluded.
There was no funding for this study, and the investigators had no relevant disclosures.
A retrospective, case-control study showed that optimal cytoreductive surgery is an independent predictor of overall survival, even when controlling for response to chemotherapy.
The findings were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10243).
Response to platinum-based chemotherapy is the strongest predictor of overall survival in advanced ovarian cancer, noted Nicholas Cardillo, MD, a gynecologic oncology fellow at the University of Iowa, Iowa City, who presented the findings at the meeting.
In recent years, a poor response to chemotherapy has sometimes been used as justification to forgo cytoreduction, Dr. Cardillo added.
He and his colleagues looked into this issue because evidence to support the practice is lacking. With their study, the researchers found that optimal cytoreduction – removing all disease of 1 cm or more – improved survival regardless of the response to chemotherapy.
“My advice right now is that debulking surgery should still be attempted in all patients with ovarian cancer because, as far as we know right now, optimal cytoreduction will improve survival,” Dr. Cardillo said in an interview. “Basically, this study argues to keep the status quo, which is to perform surgery.”
The status quo might change with future research, Dr. Cardillo acknowledged, “but as of right now, we have no evidence to support not pursuing cytoreduction in these patients.”
Study details and results
The researchers analyzed data on 234 patients who responded to platinum-based chemotherapy – meaning they had no evidence of disease for at least 6 months afterward – and 98 patients who did not respond – meaning they progressed during therapy, had stable disease, did not respond completely, or had a progression-free survival duration of less than 6 months. Subjects had stage III or IV high-grade serous ovarian cancer.
About three-quarters of responders and 57% of nonresponders had optimal surgery. Only seven patients in each group had fewer than six cycles of chemotherapy.
The mean age was 59 years in the responder group and 62 years among nonresponders. Stage IV disease, including upper-abdominal and chest involvement, was more common in the nonresponder group.
The median overall survival was 44.8 months in the responder group and 18.1 months among nonresponders (P < .001). The median overall survival was 34.2 months among patients who underwent optimal surgery and 24.8 months among those who did not (P < .001).
Predictors of survival
A multivariate analysis showed that response to chemotherapy had the greatest effect on survival, with a hazard ratio of 0.27 (P < .001).
“The second most significant predictor of overall survival was receipt of neoadjuvant chemotherapy [HR, 2.84; P < .001], which is intuitive as that is typically a marker for worse disease burden,” Dr. Cardillo said.
“But most importantly for our question is that optimal surgery is an independent significant factor in overall survival, even when controlling for other significant risk factors, including whether or not a patient responds to chemotherapy. The hazard ratio is 0.73 [P = .023], indicating a 25%-30% improvement in overall survival,” he added.
Based on these results, “surgical debulking should still be considered a component of the treatment algorithm in ovarian cancer patients who have a poor response to chemotherapy, if an optimal surgery is deemed feasible,” Dr. Cardillo concluded.
There was no funding for this study, and the investigators had no relevant disclosures.
A retrospective, case-control study showed that optimal cytoreductive surgery is an independent predictor of overall survival, even when controlling for response to chemotherapy.
The findings were presented at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10243).
Response to platinum-based chemotherapy is the strongest predictor of overall survival in advanced ovarian cancer, noted Nicholas Cardillo, MD, a gynecologic oncology fellow at the University of Iowa, Iowa City, who presented the findings at the meeting.
In recent years, a poor response to chemotherapy has sometimes been used as justification to forgo cytoreduction, Dr. Cardillo added.
He and his colleagues looked into this issue because evidence to support the practice is lacking. With their study, the researchers found that optimal cytoreduction – removing all disease of 1 cm or more – improved survival regardless of the response to chemotherapy.
“My advice right now is that debulking surgery should still be attempted in all patients with ovarian cancer because, as far as we know right now, optimal cytoreduction will improve survival,” Dr. Cardillo said in an interview. “Basically, this study argues to keep the status quo, which is to perform surgery.”
The status quo might change with future research, Dr. Cardillo acknowledged, “but as of right now, we have no evidence to support not pursuing cytoreduction in these patients.”
Study details and results
The researchers analyzed data on 234 patients who responded to platinum-based chemotherapy – meaning they had no evidence of disease for at least 6 months afterward – and 98 patients who did not respond – meaning they progressed during therapy, had stable disease, did not respond completely, or had a progression-free survival duration of less than 6 months. Subjects had stage III or IV high-grade serous ovarian cancer.
About three-quarters of responders and 57% of nonresponders had optimal surgery. Only seven patients in each group had fewer than six cycles of chemotherapy.
The mean age was 59 years in the responder group and 62 years among nonresponders. Stage IV disease, including upper-abdominal and chest involvement, was more common in the nonresponder group.
The median overall survival was 44.8 months in the responder group and 18.1 months among nonresponders (P < .001). The median overall survival was 34.2 months among patients who underwent optimal surgery and 24.8 months among those who did not (P < .001).
Predictors of survival
A multivariate analysis showed that response to chemotherapy had the greatest effect on survival, with a hazard ratio of 0.27 (P < .001).
“The second most significant predictor of overall survival was receipt of neoadjuvant chemotherapy [HR, 2.84; P < .001], which is intuitive as that is typically a marker for worse disease burden,” Dr. Cardillo said.
“But most importantly for our question is that optimal surgery is an independent significant factor in overall survival, even when controlling for other significant risk factors, including whether or not a patient responds to chemotherapy. The hazard ratio is 0.73 [P = .023], indicating a 25%-30% improvement in overall survival,” he added.
Based on these results, “surgical debulking should still be considered a component of the treatment algorithm in ovarian cancer patients who have a poor response to chemotherapy, if an optimal surgery is deemed feasible,” Dr. Cardillo concluded.
There was no funding for this study, and the investigators had no relevant disclosures.
FROM SGO 2021
Melatonin not recommended for early-stage NSCLC
There was a hint of benefit with melatonin among patients with stage III/IV NSCLC. These patients had a hazard reduction of 25% in 5-year DFS. However, the median DFS for patients with advanced disease was the same whether they received melatonin or placebo – 18 months.
In the overall study population, melatonin had no beneficial effects on quality of life, sleep, anxiety, depression, pain, or fatigue, and it did not reduce adverse events from chemotherapy or radiation.
These results were reported in EClinicalMedicine.
“In light of the results, we do not recommend the inclusion of adjuvant melatonin for patients with early-stage NSCLC. Evidence suggests there may be a benefit for those with late-stage disease,” the authors wrote. “However, because of the mixed findings observed, we recommend a follow-up randomized, controlled trial involving a larger population focusing on later-stage resected lung cancer to clarify these results.”
“I would very much like to pursue another controlled study of melatonin specifically in a group of late-stage lung cancer and possibly in other more advanced cancer types,” said lead author Dugald Seely, ND, of the Canadian College of Naturopathic Medicine in Toronto.
Study rationale and design
Melatonin has shown promise for treating patients with lung cancer, Dr. Seely and colleagues noted. Melatonin is often recommended by naturopathic doctors following lung cancer surgery, but until now there was no high-level evidence regarding the practice.
For their study, Dr. Seely and colleagues evaluated 709 patients who had undergone NSCLC resection. The patients were randomized to receive placebo (n = 353) or melatonin (n = 356) 1 hour before bedtime for 1 year. A 20-mg melatonin dose was used, which is common in clinical practice and research.
The study arms were well matched, with no “clinically meaningful” differences in demographics, surgery type, cancer type, stage of cancer, or preoperative comorbidities, according to the researchers.
The mean age in both treatment arms was 67 years. Overall, 134 participants received adjuvant chemotherapy (66 melatonin, 68 placebo), and 43 had adjuvant radiation (22 melatonin, 21 placebo).
Results
For 2-year DFS, melatonin showed an adjusted relative risk of 1.01 (95% confidence interval, 0.83-1.22; P = .94) versus placebo. The adjusted relative risk in the per-protocol analysis was 1.12 (95% CI, 0.96-1.32; P = .14.)
At 5 years, the median DFS was not reached in either treatment arm. Melatonin showed a hazard ratio of 0.97 (95% CI, 0.86-1.09; P = .84) for 5-year DFS.
Among patients with stage I-II NSCLC, the median DFS was not reached at 5 years in either treatment arm. Among patients with stage III-IV NSCLC, the median DFS was 18 months in both arms.
Melatonin showed a hazard ratio of 0.97 (95% CI, 0.85-1.11; P = .66) in patients with early-stage NSCLC and a hazard reduction of 25% (HR, 0.75; 95% CI, 0.61-0.92; P = .005) in patients with late-stage NSCLC.
For the entire cohort, there were no significant differences between treatment arms in the number, severity, or seriousness of adverse events. Likewise, there were no significant differences between the treatment arms with regard to fatigue, quality of life, or sleep at 1 or 2 years.
Dr. Seely said the most surprising thing about this study was that melatonin didn’t help with sleep.
“Since initiation of the trial, my thinking on the right dose of melatonin to support sleep has changed. Clinically, I see extended-release and, indeed, lower doses to be more effective than 20 mg nightly,” he noted.
Dr. Seely and colleagues also assessed proposed mechanisms for melatonin’s possible benefit in NSCLC but found no effect on natural killer cell cytotoxicity or phenotype and no effect on blood levels of inflammatory cytokines in a substudy of 92 patients.
This research was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation. The researchers had no relevant disclosures.
There was a hint of benefit with melatonin among patients with stage III/IV NSCLC. These patients had a hazard reduction of 25% in 5-year DFS. However, the median DFS for patients with advanced disease was the same whether they received melatonin or placebo – 18 months.
In the overall study population, melatonin had no beneficial effects on quality of life, sleep, anxiety, depression, pain, or fatigue, and it did not reduce adverse events from chemotherapy or radiation.
These results were reported in EClinicalMedicine.
“In light of the results, we do not recommend the inclusion of adjuvant melatonin for patients with early-stage NSCLC. Evidence suggests there may be a benefit for those with late-stage disease,” the authors wrote. “However, because of the mixed findings observed, we recommend a follow-up randomized, controlled trial involving a larger population focusing on later-stage resected lung cancer to clarify these results.”
“I would very much like to pursue another controlled study of melatonin specifically in a group of late-stage lung cancer and possibly in other more advanced cancer types,” said lead author Dugald Seely, ND, of the Canadian College of Naturopathic Medicine in Toronto.
Study rationale and design
Melatonin has shown promise for treating patients with lung cancer, Dr. Seely and colleagues noted. Melatonin is often recommended by naturopathic doctors following lung cancer surgery, but until now there was no high-level evidence regarding the practice.
For their study, Dr. Seely and colleagues evaluated 709 patients who had undergone NSCLC resection. The patients were randomized to receive placebo (n = 353) or melatonin (n = 356) 1 hour before bedtime for 1 year. A 20-mg melatonin dose was used, which is common in clinical practice and research.
The study arms were well matched, with no “clinically meaningful” differences in demographics, surgery type, cancer type, stage of cancer, or preoperative comorbidities, according to the researchers.
The mean age in both treatment arms was 67 years. Overall, 134 participants received adjuvant chemotherapy (66 melatonin, 68 placebo), and 43 had adjuvant radiation (22 melatonin, 21 placebo).
Results
For 2-year DFS, melatonin showed an adjusted relative risk of 1.01 (95% confidence interval, 0.83-1.22; P = .94) versus placebo. The adjusted relative risk in the per-protocol analysis was 1.12 (95% CI, 0.96-1.32; P = .14.)
At 5 years, the median DFS was not reached in either treatment arm. Melatonin showed a hazard ratio of 0.97 (95% CI, 0.86-1.09; P = .84) for 5-year DFS.
Among patients with stage I-II NSCLC, the median DFS was not reached at 5 years in either treatment arm. Among patients with stage III-IV NSCLC, the median DFS was 18 months in both arms.
Melatonin showed a hazard ratio of 0.97 (95% CI, 0.85-1.11; P = .66) in patients with early-stage NSCLC and a hazard reduction of 25% (HR, 0.75; 95% CI, 0.61-0.92; P = .005) in patients with late-stage NSCLC.
For the entire cohort, there were no significant differences between treatment arms in the number, severity, or seriousness of adverse events. Likewise, there were no significant differences between the treatment arms with regard to fatigue, quality of life, or sleep at 1 or 2 years.
Dr. Seely said the most surprising thing about this study was that melatonin didn’t help with sleep.
“Since initiation of the trial, my thinking on the right dose of melatonin to support sleep has changed. Clinically, I see extended-release and, indeed, lower doses to be more effective than 20 mg nightly,” he noted.
Dr. Seely and colleagues also assessed proposed mechanisms for melatonin’s possible benefit in NSCLC but found no effect on natural killer cell cytotoxicity or phenotype and no effect on blood levels of inflammatory cytokines in a substudy of 92 patients.
This research was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation. The researchers had no relevant disclosures.
There was a hint of benefit with melatonin among patients with stage III/IV NSCLC. These patients had a hazard reduction of 25% in 5-year DFS. However, the median DFS for patients with advanced disease was the same whether they received melatonin or placebo – 18 months.
In the overall study population, melatonin had no beneficial effects on quality of life, sleep, anxiety, depression, pain, or fatigue, and it did not reduce adverse events from chemotherapy or radiation.
These results were reported in EClinicalMedicine.
“In light of the results, we do not recommend the inclusion of adjuvant melatonin for patients with early-stage NSCLC. Evidence suggests there may be a benefit for those with late-stage disease,” the authors wrote. “However, because of the mixed findings observed, we recommend a follow-up randomized, controlled trial involving a larger population focusing on later-stage resected lung cancer to clarify these results.”
“I would very much like to pursue another controlled study of melatonin specifically in a group of late-stage lung cancer and possibly in other more advanced cancer types,” said lead author Dugald Seely, ND, of the Canadian College of Naturopathic Medicine in Toronto.
Study rationale and design
Melatonin has shown promise for treating patients with lung cancer, Dr. Seely and colleagues noted. Melatonin is often recommended by naturopathic doctors following lung cancer surgery, but until now there was no high-level evidence regarding the practice.
For their study, Dr. Seely and colleagues evaluated 709 patients who had undergone NSCLC resection. The patients were randomized to receive placebo (n = 353) or melatonin (n = 356) 1 hour before bedtime for 1 year. A 20-mg melatonin dose was used, which is common in clinical practice and research.
The study arms were well matched, with no “clinically meaningful” differences in demographics, surgery type, cancer type, stage of cancer, or preoperative comorbidities, according to the researchers.
The mean age in both treatment arms was 67 years. Overall, 134 participants received adjuvant chemotherapy (66 melatonin, 68 placebo), and 43 had adjuvant radiation (22 melatonin, 21 placebo).
Results
For 2-year DFS, melatonin showed an adjusted relative risk of 1.01 (95% confidence interval, 0.83-1.22; P = .94) versus placebo. The adjusted relative risk in the per-protocol analysis was 1.12 (95% CI, 0.96-1.32; P = .14.)
At 5 years, the median DFS was not reached in either treatment arm. Melatonin showed a hazard ratio of 0.97 (95% CI, 0.86-1.09; P = .84) for 5-year DFS.
Among patients with stage I-II NSCLC, the median DFS was not reached at 5 years in either treatment arm. Among patients with stage III-IV NSCLC, the median DFS was 18 months in both arms.
Melatonin showed a hazard ratio of 0.97 (95% CI, 0.85-1.11; P = .66) in patients with early-stage NSCLC and a hazard reduction of 25% (HR, 0.75; 95% CI, 0.61-0.92; P = .005) in patients with late-stage NSCLC.
For the entire cohort, there were no significant differences between treatment arms in the number, severity, or seriousness of adverse events. Likewise, there were no significant differences between the treatment arms with regard to fatigue, quality of life, or sleep at 1 or 2 years.
Dr. Seely said the most surprising thing about this study was that melatonin didn’t help with sleep.
“Since initiation of the trial, my thinking on the right dose of melatonin to support sleep has changed. Clinically, I see extended-release and, indeed, lower doses to be more effective than 20 mg nightly,” he noted.
Dr. Seely and colleagues also assessed proposed mechanisms for melatonin’s possible benefit in NSCLC but found no effect on natural killer cell cytotoxicity or phenotype and no effect on blood levels of inflammatory cytokines in a substudy of 92 patients.
This research was funded by the Lotte and John Hecht Memorial Foundation and the Gateway for Cancer Research Foundation. The researchers had no relevant disclosures.
FROM ECLINICALMEDICINE
Delaying surgery didn’t impact survival in early-stage cervical cancer
in the National Cancer Database.
The 5-year overall survival rate was 85.7% among women who had radical hysterectomy and lymphadenectomy within 4 weeks of diagnosis, 86.6% among those who had the same surgery 4-8 weeks after diagnosis, and 89.6% among those who had surgery 8-12 weeks after diagnosis (P = .12).
“For patients with clinical stage I cervical carcinoma undergoing radical hysterectomy, we found no evidence of a detrimental effect of waiting time (up to 12 weeks from diagnosis) on overall survival,” the study investigators reported in a poster at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer.
The investigators looked at the issue of surgical wait times because of surgery delays due to the COVID-19 pandemic, according to investigator Dimitrios Nasioudis, MD, of the University of Pennsylvania in Philadelphia.
“We wanted to see if there was a real impact in the survival of patients,” Dr. Nasioudis said in an interview. He added that “many times, there is a question of when to perform surgery,” especially when patients need medical optimization.
Dr. Nasioudis called the findings “reassuring” and said “waiting up to 3 or 4 months is reasonable.”
Still, the investigators plan to validate the results with more granular patient-level institutional data, he said. Given the limits of the database, there was no information on tumor relapse or cause of death and no central pathology review.
Study details
The study included 4,782 patients who underwent primary radical hysterectomy with lymphadenectomy. Patients had clinical stage I adenocarcinoma, squamous, or adenosquamous carcinoma of the cervix, with no history of another tumor or other cervical surgery.
The median time to surgery was 34 days across the study population. Patients were divided into three groups according to the timing of their surgery:
- Group 1 included 1,823 (38.1%) patients who had surgery less than 4 weeks from diagnosis.
- Group 2 included 2,207 (46.2%) patients who had surgery 4-8 weeks from diagnosis.
- Group 3 included 752 (15.7%) patients who had surgery 8-12 weeks from diagnosis.
Patients in group 1 had a higher rate of positive lymph nodes, compared with patients in groups 2 and 3 (18.4%, 15.6%, and 14.7%, respectively; P = .014). Patients in group 1 also had a higher incidence of lymphovascular space invasion (42.1%, 38.1%, and 33%; P = .007) and a higher rate of positive surgical margins (6.3%, 5.2%, and 3.9%; P = .047).
Group 1 patients “had more aggressive features,” which could explain why they had surgery within a month, Dr. Nasioudis said.
Patients in groups 3 and 2 were more likely to have government insurance, compared with patients in group 1 (35.6%, 31.6%, and 24.6%, respectively P < .001). Group 3 patients were more likely than those in groups 2 and 1 to have comorbidities (14.2%, 11.6%, and 10.5%; P = .29).
However, there were no survival differences between groups in a multivariate analysis controlling for confounders, which included tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race, and comorbidities. Furthermore, in a stratified analysis based on tumor extent, the timing of surgery had no impact on survival.
Dr. Nasioudis said he suspects access to care was an issue for some women, and there were likely delays for medical optimization.
Access to gynecologic oncology services at the University of Pennsylvania is “pretty easy,” he said, so delays are usually related to medical optimization, but that’s not always the case in underserved areas of the United States.
There was no funding for this study, and the investigators didn’t have any disclosures.
in the National Cancer Database.
The 5-year overall survival rate was 85.7% among women who had radical hysterectomy and lymphadenectomy within 4 weeks of diagnosis, 86.6% among those who had the same surgery 4-8 weeks after diagnosis, and 89.6% among those who had surgery 8-12 weeks after diagnosis (P = .12).
“For patients with clinical stage I cervical carcinoma undergoing radical hysterectomy, we found no evidence of a detrimental effect of waiting time (up to 12 weeks from diagnosis) on overall survival,” the study investigators reported in a poster at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer.
The investigators looked at the issue of surgical wait times because of surgery delays due to the COVID-19 pandemic, according to investigator Dimitrios Nasioudis, MD, of the University of Pennsylvania in Philadelphia.
“We wanted to see if there was a real impact in the survival of patients,” Dr. Nasioudis said in an interview. He added that “many times, there is a question of when to perform surgery,” especially when patients need medical optimization.
Dr. Nasioudis called the findings “reassuring” and said “waiting up to 3 or 4 months is reasonable.”
Still, the investigators plan to validate the results with more granular patient-level institutional data, he said. Given the limits of the database, there was no information on tumor relapse or cause of death and no central pathology review.
Study details
The study included 4,782 patients who underwent primary radical hysterectomy with lymphadenectomy. Patients had clinical stage I adenocarcinoma, squamous, or adenosquamous carcinoma of the cervix, with no history of another tumor or other cervical surgery.
The median time to surgery was 34 days across the study population. Patients were divided into three groups according to the timing of their surgery:
- Group 1 included 1,823 (38.1%) patients who had surgery less than 4 weeks from diagnosis.
- Group 2 included 2,207 (46.2%) patients who had surgery 4-8 weeks from diagnosis.
- Group 3 included 752 (15.7%) patients who had surgery 8-12 weeks from diagnosis.
Patients in group 1 had a higher rate of positive lymph nodes, compared with patients in groups 2 and 3 (18.4%, 15.6%, and 14.7%, respectively; P = .014). Patients in group 1 also had a higher incidence of lymphovascular space invasion (42.1%, 38.1%, and 33%; P = .007) and a higher rate of positive surgical margins (6.3%, 5.2%, and 3.9%; P = .047).
Group 1 patients “had more aggressive features,” which could explain why they had surgery within a month, Dr. Nasioudis said.
Patients in groups 3 and 2 were more likely to have government insurance, compared with patients in group 1 (35.6%, 31.6%, and 24.6%, respectively P < .001). Group 3 patients were more likely than those in groups 2 and 1 to have comorbidities (14.2%, 11.6%, and 10.5%; P = .29).
However, there were no survival differences between groups in a multivariate analysis controlling for confounders, which included tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race, and comorbidities. Furthermore, in a stratified analysis based on tumor extent, the timing of surgery had no impact on survival.
Dr. Nasioudis said he suspects access to care was an issue for some women, and there were likely delays for medical optimization.
Access to gynecologic oncology services at the University of Pennsylvania is “pretty easy,” he said, so delays are usually related to medical optimization, but that’s not always the case in underserved areas of the United States.
There was no funding for this study, and the investigators didn’t have any disclosures.
in the National Cancer Database.
The 5-year overall survival rate was 85.7% among women who had radical hysterectomy and lymphadenectomy within 4 weeks of diagnosis, 86.6% among those who had the same surgery 4-8 weeks after diagnosis, and 89.6% among those who had surgery 8-12 weeks after diagnosis (P = .12).
“For patients with clinical stage I cervical carcinoma undergoing radical hysterectomy, we found no evidence of a detrimental effect of waiting time (up to 12 weeks from diagnosis) on overall survival,” the study investigators reported in a poster at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer.
The investigators looked at the issue of surgical wait times because of surgery delays due to the COVID-19 pandemic, according to investigator Dimitrios Nasioudis, MD, of the University of Pennsylvania in Philadelphia.
“We wanted to see if there was a real impact in the survival of patients,” Dr. Nasioudis said in an interview. He added that “many times, there is a question of when to perform surgery,” especially when patients need medical optimization.
Dr. Nasioudis called the findings “reassuring” and said “waiting up to 3 or 4 months is reasonable.”
Still, the investigators plan to validate the results with more granular patient-level institutional data, he said. Given the limits of the database, there was no information on tumor relapse or cause of death and no central pathology review.
Study details
The study included 4,782 patients who underwent primary radical hysterectomy with lymphadenectomy. Patients had clinical stage I adenocarcinoma, squamous, or adenosquamous carcinoma of the cervix, with no history of another tumor or other cervical surgery.
The median time to surgery was 34 days across the study population. Patients were divided into three groups according to the timing of their surgery:
- Group 1 included 1,823 (38.1%) patients who had surgery less than 4 weeks from diagnosis.
- Group 2 included 2,207 (46.2%) patients who had surgery 4-8 weeks from diagnosis.
- Group 3 included 752 (15.7%) patients who had surgery 8-12 weeks from diagnosis.
Patients in group 1 had a higher rate of positive lymph nodes, compared with patients in groups 2 and 3 (18.4%, 15.6%, and 14.7%, respectively; P = .014). Patients in group 1 also had a higher incidence of lymphovascular space invasion (42.1%, 38.1%, and 33%; P = .007) and a higher rate of positive surgical margins (6.3%, 5.2%, and 3.9%; P = .047).
Group 1 patients “had more aggressive features,” which could explain why they had surgery within a month, Dr. Nasioudis said.
Patients in groups 3 and 2 were more likely to have government insurance, compared with patients in group 1 (35.6%, 31.6%, and 24.6%, respectively P < .001). Group 3 patients were more likely than those in groups 2 and 1 to have comorbidities (14.2%, 11.6%, and 10.5%; P = .29).
However, there were no survival differences between groups in a multivariate analysis controlling for confounders, which included tumor size, histology and extension, status of lymph nodes, receipt of radiotherapy, patient age, insurance, race, and comorbidities. Furthermore, in a stratified analysis based on tumor extent, the timing of surgery had no impact on survival.
Dr. Nasioudis said he suspects access to care was an issue for some women, and there were likely delays for medical optimization.
Access to gynecologic oncology services at the University of Pennsylvania is “pretty easy,” he said, so delays are usually related to medical optimization, but that’s not always the case in underserved areas of the United States.
There was no funding for this study, and the investigators didn’t have any disclosures.
FROM SGO 2021
Expert recommendations for targeted therapies in advanced NSCLC
The guidelines, jointly released by the American Society of Clinical Oncology (ASCO) and Ontario Health (OH), were published in the Journal of Clinical Oncology. The recommendations are based on results from 54 studies published or presented from Dec. 2015 to May 2020.
The new guidelines supplant ASCO’s 2017 guidelines on stage IV NSCLC. Several driver mutations were touched upon in the 2017 document, but their corresponding targeted therapies were not recommended as first-line treatment.
With substantial progress in targeted therapies since 2017, treatment decision-making in 2021 focuses on the molecular signatures of tumors and PD-L1 score, according to the authors of the current guidelines, Nasser Hanna, MD, of Indiana University, Indianapolis, and colleagues.
“All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations,” the authors wrote.
They noted that about a third of patients with NSCLC have known targetable genetic alterations. The Food and Drug Administration has approved therapeutics targeting seven alterations: EGFR and ALK alterations, ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions.
EGFR-mutant NSCLC
The authors’ recommendation for osimertinib as first-line therapy applies to patients who have EGFR-activating mutations in exon 19 (deletion), exon 21 L858R, or exon 20 T790M.
The authors also said osimertinib is an option for patients with other EGFR mutations. Alternatively, these patients can receive afatinib or treatments outlined in the ASCO/OH nondriver mutation guideline, which was published in the Journal of Clinical Oncology in 2020.
If osimertinib is not available for first-line treatment, other options include gefitinib, erlotinib, icotinib, gefitinib plus chemotherapy, dacomitinib, afatinib, erlotinib plus bevacizumab, or erlotinib plus ramucirumab.
The authors recommend osimertinib in the second-line setting for patients who did not receive osimertinib initially and who have a T790M mutation at the time of progression. For patients who have progressed on EGFR tyrosine kinase inhibitors and have no T790M mutation or if their disease has progressed on osimertinib, second-line treatment should be based on the ASCO/OH nondriver mutation guideline, according to Dr. Hanna and colleagues.
ALK-mutant NSCLC
For patients with ALK alterations, the authors recommend alectinib or brigatinib as first-line treatment. If these agents are not available, ceritinib or crizotinib should be offered.
In the second-line setting, if alectinib or brigatinib were given initially, lorlatinib may be offered. If crizotinib was given as first-line therapy, then alectinib, brigatinib, or ceritinib should be offered.
If crizotinib was given in the first-line setting and alectinib, brigatinib, or ceritinib were given in the second-line setting, third-line treatment should be lorlatinib or standard treatment based on the ASCO/OH nondriver mutation guideline.
Other mutations
For stage IV NSCLC patients with alterations in ROS1, BRAF, RET, MET, or NTRK, the authors recommend either targeted or standard nontargeted therapy upfront, with the approach not given first-line used in the second line.
“It is unknown if improved outcomes would be seen when comparing standard nondriver mutation treatment with using the targeted therapy in the first- or second-line setting,” the authors wrote.
They noted that the recommendations for EGFR-activating mutations and ALK fusions are based on results from phase 3 trials, but recommendations for other targetable mutations are supported by phase 2 single-arm data.
The authors also noted promising reports for agents aimed at other molecular targets, including aberrations in KRAS, HER2, and NRG-1.
“Although there are insufficient data to recommend targeted therapy in these and other subgroups at the time of this guideline update, we anticipate rapid evolution of the evidence and availability of targeted therapies in these subgroups of patients soon,” the authors wrote.
Cost considerations
The authors noted that cost is a consideration when deciding on treatment, and costs can vary widely. According to 2020 Medicare drug prices, the monthly cost of ramucirumab was $61, while the monthly cost of ceritinib was $21,107.
“Increasingly, individuals with cancer are required to pay a larger proportion of their treatment costs through deductibles and coinsurance. Higher patient out-of-pocket costs have been shown to be a barrier to initiating and adhering to recommended cancer treatments,” the authors wrote.
“Discussion of cost can be an important part of shared decision-making. Clinicians should discuss with patients the use of less expensive alternatives when it is practical and feasible for treatment of the patient’s disease,” they added.
The guidelines were funded by ASCO. The authors had numerous disclosures, including Dr. Hanna, who disclosed relationships with UpToDate, Merck KGaA, Bristol-Myers Squibb, AstraZeneca/MedImmune, Genentech, and BeyondSpring Pharmaceuticals.
The guidelines, jointly released by the American Society of Clinical Oncology (ASCO) and Ontario Health (OH), were published in the Journal of Clinical Oncology. The recommendations are based on results from 54 studies published or presented from Dec. 2015 to May 2020.
The new guidelines supplant ASCO’s 2017 guidelines on stage IV NSCLC. Several driver mutations were touched upon in the 2017 document, but their corresponding targeted therapies were not recommended as first-line treatment.
With substantial progress in targeted therapies since 2017, treatment decision-making in 2021 focuses on the molecular signatures of tumors and PD-L1 score, according to the authors of the current guidelines, Nasser Hanna, MD, of Indiana University, Indianapolis, and colleagues.
“All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations,” the authors wrote.
They noted that about a third of patients with NSCLC have known targetable genetic alterations. The Food and Drug Administration has approved therapeutics targeting seven alterations: EGFR and ALK alterations, ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions.
EGFR-mutant NSCLC
The authors’ recommendation for osimertinib as first-line therapy applies to patients who have EGFR-activating mutations in exon 19 (deletion), exon 21 L858R, or exon 20 T790M.
The authors also said osimertinib is an option for patients with other EGFR mutations. Alternatively, these patients can receive afatinib or treatments outlined in the ASCO/OH nondriver mutation guideline, which was published in the Journal of Clinical Oncology in 2020.
If osimertinib is not available for first-line treatment, other options include gefitinib, erlotinib, icotinib, gefitinib plus chemotherapy, dacomitinib, afatinib, erlotinib plus bevacizumab, or erlotinib plus ramucirumab.
The authors recommend osimertinib in the second-line setting for patients who did not receive osimertinib initially and who have a T790M mutation at the time of progression. For patients who have progressed on EGFR tyrosine kinase inhibitors and have no T790M mutation or if their disease has progressed on osimertinib, second-line treatment should be based on the ASCO/OH nondriver mutation guideline, according to Dr. Hanna and colleagues.
ALK-mutant NSCLC
For patients with ALK alterations, the authors recommend alectinib or brigatinib as first-line treatment. If these agents are not available, ceritinib or crizotinib should be offered.
In the second-line setting, if alectinib or brigatinib were given initially, lorlatinib may be offered. If crizotinib was given as first-line therapy, then alectinib, brigatinib, or ceritinib should be offered.
If crizotinib was given in the first-line setting and alectinib, brigatinib, or ceritinib were given in the second-line setting, third-line treatment should be lorlatinib or standard treatment based on the ASCO/OH nondriver mutation guideline.
Other mutations
For stage IV NSCLC patients with alterations in ROS1, BRAF, RET, MET, or NTRK, the authors recommend either targeted or standard nontargeted therapy upfront, with the approach not given first-line used in the second line.
“It is unknown if improved outcomes would be seen when comparing standard nondriver mutation treatment with using the targeted therapy in the first- or second-line setting,” the authors wrote.
They noted that the recommendations for EGFR-activating mutations and ALK fusions are based on results from phase 3 trials, but recommendations for other targetable mutations are supported by phase 2 single-arm data.
The authors also noted promising reports for agents aimed at other molecular targets, including aberrations in KRAS, HER2, and NRG-1.
“Although there are insufficient data to recommend targeted therapy in these and other subgroups at the time of this guideline update, we anticipate rapid evolution of the evidence and availability of targeted therapies in these subgroups of patients soon,” the authors wrote.
Cost considerations
The authors noted that cost is a consideration when deciding on treatment, and costs can vary widely. According to 2020 Medicare drug prices, the monthly cost of ramucirumab was $61, while the monthly cost of ceritinib was $21,107.
“Increasingly, individuals with cancer are required to pay a larger proportion of their treatment costs through deductibles and coinsurance. Higher patient out-of-pocket costs have been shown to be a barrier to initiating and adhering to recommended cancer treatments,” the authors wrote.
“Discussion of cost can be an important part of shared decision-making. Clinicians should discuss with patients the use of less expensive alternatives when it is practical and feasible for treatment of the patient’s disease,” they added.
The guidelines were funded by ASCO. The authors had numerous disclosures, including Dr. Hanna, who disclosed relationships with UpToDate, Merck KGaA, Bristol-Myers Squibb, AstraZeneca/MedImmune, Genentech, and BeyondSpring Pharmaceuticals.
The guidelines, jointly released by the American Society of Clinical Oncology (ASCO) and Ontario Health (OH), were published in the Journal of Clinical Oncology. The recommendations are based on results from 54 studies published or presented from Dec. 2015 to May 2020.
The new guidelines supplant ASCO’s 2017 guidelines on stage IV NSCLC. Several driver mutations were touched upon in the 2017 document, but their corresponding targeted therapies were not recommended as first-line treatment.
With substantial progress in targeted therapies since 2017, treatment decision-making in 2021 focuses on the molecular signatures of tumors and PD-L1 score, according to the authors of the current guidelines, Nasser Hanna, MD, of Indiana University, Indianapolis, and colleagues.
“All patients with nonsquamous NSCLC should have the results of testing for potentially targetable mutations (alterations) before implementing therapy for advanced lung cancer, regardless of smoking status recommendations,” the authors wrote.
They noted that about a third of patients with NSCLC have known targetable genetic alterations. The Food and Drug Administration has approved therapeutics targeting seven alterations: EGFR and ALK alterations, ROS-1 fusions, BRAF V600e mutations, RET fusions, MET exon 14 skipping mutations, and NTRK fusions.
EGFR-mutant NSCLC
The authors’ recommendation for osimertinib as first-line therapy applies to patients who have EGFR-activating mutations in exon 19 (deletion), exon 21 L858R, or exon 20 T790M.
The authors also said osimertinib is an option for patients with other EGFR mutations. Alternatively, these patients can receive afatinib or treatments outlined in the ASCO/OH nondriver mutation guideline, which was published in the Journal of Clinical Oncology in 2020.
If osimertinib is not available for first-line treatment, other options include gefitinib, erlotinib, icotinib, gefitinib plus chemotherapy, dacomitinib, afatinib, erlotinib plus bevacizumab, or erlotinib plus ramucirumab.
The authors recommend osimertinib in the second-line setting for patients who did not receive osimertinib initially and who have a T790M mutation at the time of progression. For patients who have progressed on EGFR tyrosine kinase inhibitors and have no T790M mutation or if their disease has progressed on osimertinib, second-line treatment should be based on the ASCO/OH nondriver mutation guideline, according to Dr. Hanna and colleagues.
ALK-mutant NSCLC
For patients with ALK alterations, the authors recommend alectinib or brigatinib as first-line treatment. If these agents are not available, ceritinib or crizotinib should be offered.
In the second-line setting, if alectinib or brigatinib were given initially, lorlatinib may be offered. If crizotinib was given as first-line therapy, then alectinib, brigatinib, or ceritinib should be offered.
If crizotinib was given in the first-line setting and alectinib, brigatinib, or ceritinib were given in the second-line setting, third-line treatment should be lorlatinib or standard treatment based on the ASCO/OH nondriver mutation guideline.
Other mutations
For stage IV NSCLC patients with alterations in ROS1, BRAF, RET, MET, or NTRK, the authors recommend either targeted or standard nontargeted therapy upfront, with the approach not given first-line used in the second line.
“It is unknown if improved outcomes would be seen when comparing standard nondriver mutation treatment with using the targeted therapy in the first- or second-line setting,” the authors wrote.
They noted that the recommendations for EGFR-activating mutations and ALK fusions are based on results from phase 3 trials, but recommendations for other targetable mutations are supported by phase 2 single-arm data.
The authors also noted promising reports for agents aimed at other molecular targets, including aberrations in KRAS, HER2, and NRG-1.
“Although there are insufficient data to recommend targeted therapy in these and other subgroups at the time of this guideline update, we anticipate rapid evolution of the evidence and availability of targeted therapies in these subgroups of patients soon,” the authors wrote.
Cost considerations
The authors noted that cost is a consideration when deciding on treatment, and costs can vary widely. According to 2020 Medicare drug prices, the monthly cost of ramucirumab was $61, while the monthly cost of ceritinib was $21,107.
“Increasingly, individuals with cancer are required to pay a larger proportion of their treatment costs through deductibles and coinsurance. Higher patient out-of-pocket costs have been shown to be a barrier to initiating and adhering to recommended cancer treatments,” the authors wrote.
“Discussion of cost can be an important part of shared decision-making. Clinicians should discuss with patients the use of less expensive alternatives when it is practical and feasible for treatment of the patient’s disease,” they added.
The guidelines were funded by ASCO. The authors had numerous disclosures, including Dr. Hanna, who disclosed relationships with UpToDate, Merck KGaA, Bristol-Myers Squibb, AstraZeneca/MedImmune, Genentech, and BeyondSpring Pharmaceuticals.
FROM JOURNAL OF CLINICAL ONCOLOGY
Ovarian cancer prevention: How patients decide on surgery
Investigators interviewed 24 premenopausal women with BRCA mutations who were considering prophylactic surgery. Responses showed that women who prioritized cancer risk reduction opted for risk-reducing salpingo-oophorectomy (RRSO), while those who were more concerned about the effects of surgical menopause opted for risk-reducing early salpingectomy with delayed oophorectomy (RRESDO). Factors such as past surgical experience influenced patients’ decisions as well.
The women were participants in the PROTECTOR trial, which was designed to determine the impact of RRESDO on sexual function by comparing RRESDO, RRSO, and no surgery. Study participants made their own decisions regarding surgery, and the interviews with 24 participants provided insight into how patients made their decisions.
Faiza Gaba, MBBS, PhD, of Queen Mary University of London, and colleagues reviewed the results in the Journal of Medical Genetics.
“I think what is most important is that even though this is a tough decision women are being given, they are being given options that allow them to make up their own minds with support from health care providers,” said Barbara A. Goff, MD, of the University of Washington, Seattle, when asked to comment on this research.
Study details and results
The investigators interviewed 24 women aged 34-46 years. Fourteen patients were BRCA1 carriers, and 10 were BRCA2 carriers. Twenty-two women were White, and two were Asian. Nineteen women were married, and four were nulliparous.
The interviews lasted a mean of 55 minutes and were conducted with a predeveloped topic guide.
Eleven of the women interviewed opted for RRESDO, seven opted for RRSO, and six decided against prophylactic surgery. Four women who had previous breast cancer all opted for ovarian cancer prevention surgery.
Among the 18 women who chose surgery, 16 had completed childbearing, and 2 didn’t want children. Among the six women who decided against surgery, four had not completed childbearing, one was unsure of which procedure to choose, and the sixth had strong feelings against removing healthy tissue.
The 11 women who chose RRESDO did so because of concerns about early menopause following oophorectomy, particularly low mood, sexual dysfunction, and poorer quality of life. They were also more likely to have had a previous positive surgical experience, so they were not as concerned about a two-step surgery.
Women who chose RRSO were motivated by a strong family history of ovarian cancer, fear of dying, concurrent benign gynecological issues, lack of screening for ovarian cancer, and physician advice.
Nine women also opted for risk-reducing mastectomy (RRM), which was deemed a more difficult decision than prophylactic ovarian cancer surgery.
Women who decided against RRM did so because they hadn’t completed childbearing, they were concerned about recovery time and the psychological effects of the surgery, or they had confidence in breast cancer screening and treatment.
Among women who chose RRM, two highlighted lack of health care professional support for deciding against reconstruction. One interviewee regretted opting for flap reconstruction due to the resultant cosmetic appearance and chronic pain but did not regret RRM.
Fifteen women said they would have preferred combined RRM and ovarian cancer prevention in one surgery, due to less anxiety, less waiting, fewer appointments, less time off work, and a single surgical recovery.
The women advised fellow BRCA carriers to avoid time pressure with surgical decision-making, talk to other BRCA carriers, do personal research, and ask for second opinions if not satisfied. They also said the opportunity to ask experts questions and meet other BRCA carriers face-to-face was more helpful than online support groups. Women managed in specialist settings said they received better care, better access to hormone replacement therapy, and were more satisfied.
High-risk women need to be supported by a multidisciplinary team of geneticists, gynecologists/oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists, and specialist nurses, the investigators wrote.
This study was funded by the Rosetrees Trust and Barts Charity. The authors disclosed relationships with AstraZeneca, Merck, Cancer Research UK, The Eve Appeal, Israel National Institute for Health Policy Research, and the UK National Health Service. Dr. Goff has no relevant disclosures.
Investigators interviewed 24 premenopausal women with BRCA mutations who were considering prophylactic surgery. Responses showed that women who prioritized cancer risk reduction opted for risk-reducing salpingo-oophorectomy (RRSO), while those who were more concerned about the effects of surgical menopause opted for risk-reducing early salpingectomy with delayed oophorectomy (RRESDO). Factors such as past surgical experience influenced patients’ decisions as well.
The women were participants in the PROTECTOR trial, which was designed to determine the impact of RRESDO on sexual function by comparing RRESDO, RRSO, and no surgery. Study participants made their own decisions regarding surgery, and the interviews with 24 participants provided insight into how patients made their decisions.
Faiza Gaba, MBBS, PhD, of Queen Mary University of London, and colleagues reviewed the results in the Journal of Medical Genetics.
“I think what is most important is that even though this is a tough decision women are being given, they are being given options that allow them to make up their own minds with support from health care providers,” said Barbara A. Goff, MD, of the University of Washington, Seattle, when asked to comment on this research.
Study details and results
The investigators interviewed 24 women aged 34-46 years. Fourteen patients were BRCA1 carriers, and 10 were BRCA2 carriers. Twenty-two women were White, and two were Asian. Nineteen women were married, and four were nulliparous.
The interviews lasted a mean of 55 minutes and were conducted with a predeveloped topic guide.
Eleven of the women interviewed opted for RRESDO, seven opted for RRSO, and six decided against prophylactic surgery. Four women who had previous breast cancer all opted for ovarian cancer prevention surgery.
Among the 18 women who chose surgery, 16 had completed childbearing, and 2 didn’t want children. Among the six women who decided against surgery, four had not completed childbearing, one was unsure of which procedure to choose, and the sixth had strong feelings against removing healthy tissue.
The 11 women who chose RRESDO did so because of concerns about early menopause following oophorectomy, particularly low mood, sexual dysfunction, and poorer quality of life. They were also more likely to have had a previous positive surgical experience, so they were not as concerned about a two-step surgery.
Women who chose RRSO were motivated by a strong family history of ovarian cancer, fear of dying, concurrent benign gynecological issues, lack of screening for ovarian cancer, and physician advice.
Nine women also opted for risk-reducing mastectomy (RRM), which was deemed a more difficult decision than prophylactic ovarian cancer surgery.
Women who decided against RRM did so because they hadn’t completed childbearing, they were concerned about recovery time and the psychological effects of the surgery, or they had confidence in breast cancer screening and treatment.
Among women who chose RRM, two highlighted lack of health care professional support for deciding against reconstruction. One interviewee regretted opting for flap reconstruction due to the resultant cosmetic appearance and chronic pain but did not regret RRM.
Fifteen women said they would have preferred combined RRM and ovarian cancer prevention in one surgery, due to less anxiety, less waiting, fewer appointments, less time off work, and a single surgical recovery.
The women advised fellow BRCA carriers to avoid time pressure with surgical decision-making, talk to other BRCA carriers, do personal research, and ask for second opinions if not satisfied. They also said the opportunity to ask experts questions and meet other BRCA carriers face-to-face was more helpful than online support groups. Women managed in specialist settings said they received better care, better access to hormone replacement therapy, and were more satisfied.
High-risk women need to be supported by a multidisciplinary team of geneticists, gynecologists/oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists, and specialist nurses, the investigators wrote.
This study was funded by the Rosetrees Trust and Barts Charity. The authors disclosed relationships with AstraZeneca, Merck, Cancer Research UK, The Eve Appeal, Israel National Institute for Health Policy Research, and the UK National Health Service. Dr. Goff has no relevant disclosures.
Investigators interviewed 24 premenopausal women with BRCA mutations who were considering prophylactic surgery. Responses showed that women who prioritized cancer risk reduction opted for risk-reducing salpingo-oophorectomy (RRSO), while those who were more concerned about the effects of surgical menopause opted for risk-reducing early salpingectomy with delayed oophorectomy (RRESDO). Factors such as past surgical experience influenced patients’ decisions as well.
The women were participants in the PROTECTOR trial, which was designed to determine the impact of RRESDO on sexual function by comparing RRESDO, RRSO, and no surgery. Study participants made their own decisions regarding surgery, and the interviews with 24 participants provided insight into how patients made their decisions.
Faiza Gaba, MBBS, PhD, of Queen Mary University of London, and colleagues reviewed the results in the Journal of Medical Genetics.
“I think what is most important is that even though this is a tough decision women are being given, they are being given options that allow them to make up their own minds with support from health care providers,” said Barbara A. Goff, MD, of the University of Washington, Seattle, when asked to comment on this research.
Study details and results
The investigators interviewed 24 women aged 34-46 years. Fourteen patients were BRCA1 carriers, and 10 were BRCA2 carriers. Twenty-two women were White, and two were Asian. Nineteen women were married, and four were nulliparous.
The interviews lasted a mean of 55 minutes and were conducted with a predeveloped topic guide.
Eleven of the women interviewed opted for RRESDO, seven opted for RRSO, and six decided against prophylactic surgery. Four women who had previous breast cancer all opted for ovarian cancer prevention surgery.
Among the 18 women who chose surgery, 16 had completed childbearing, and 2 didn’t want children. Among the six women who decided against surgery, four had not completed childbearing, one was unsure of which procedure to choose, and the sixth had strong feelings against removing healthy tissue.
The 11 women who chose RRESDO did so because of concerns about early menopause following oophorectomy, particularly low mood, sexual dysfunction, and poorer quality of life. They were also more likely to have had a previous positive surgical experience, so they were not as concerned about a two-step surgery.
Women who chose RRSO were motivated by a strong family history of ovarian cancer, fear of dying, concurrent benign gynecological issues, lack of screening for ovarian cancer, and physician advice.
Nine women also opted for risk-reducing mastectomy (RRM), which was deemed a more difficult decision than prophylactic ovarian cancer surgery.
Women who decided against RRM did so because they hadn’t completed childbearing, they were concerned about recovery time and the psychological effects of the surgery, or they had confidence in breast cancer screening and treatment.
Among women who chose RRM, two highlighted lack of health care professional support for deciding against reconstruction. One interviewee regretted opting for flap reconstruction due to the resultant cosmetic appearance and chronic pain but did not regret RRM.
Fifteen women said they would have preferred combined RRM and ovarian cancer prevention in one surgery, due to less anxiety, less waiting, fewer appointments, less time off work, and a single surgical recovery.
The women advised fellow BRCA carriers to avoid time pressure with surgical decision-making, talk to other BRCA carriers, do personal research, and ask for second opinions if not satisfied. They also said the opportunity to ask experts questions and meet other BRCA carriers face-to-face was more helpful than online support groups. Women managed in specialist settings said they received better care, better access to hormone replacement therapy, and were more satisfied.
High-risk women need to be supported by a multidisciplinary team of geneticists, gynecologists/oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists, and specialist nurses, the investigators wrote.
This study was funded by the Rosetrees Trust and Barts Charity. The authors disclosed relationships with AstraZeneca, Merck, Cancer Research UK, The Eve Appeal, Israel National Institute for Health Policy Research, and the UK National Health Service. Dr. Goff has no relevant disclosures.
FROM THE JOURNAL OF MEDICAL GENETICS
Age should not be a barrier to aggressive esophageal cancer treatment
Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.
Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.
Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. the investigators concluded.
The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.
Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.
However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.
Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.
“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.
The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.
The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.
A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.
They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”
Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.
“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.
“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.
Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.
Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.
There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.
Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.
Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. the investigators concluded.
The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.
Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.
However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.
Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.
“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.
The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.
The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.
A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.
They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”
Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.
“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.
“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.
Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.
Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.
There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
Neoadjuvant chemoradiation plus esophagectomy can be performed safely in well-selected older patients with locally advanced esophageal or esophagogastric junction cancer, according to a review 282 patients treated from 2004 through 2019 at Ochsner Medical Center, New Orleans.
Although guidelines recommend curative-intent neoadjuvant chemoradiation (NACR) followed by surgical resection, it’s been demonstrated in several studies that “older patients with potentially curable stage II and III disease are often not considered” for the approach out of concern that they will not tolerate it, said investigators led by W. Peter Sawyer, MD, a surgery resident at Ochsner.
Outcomes, however, were comparable in the study when 188 patients aged younger than 70 years were compared with 94 patients aged 70 years or older, including 4 who were over 80 years old. the investigators concluded.
The patients had NACR followed by esophagectomy mostly for stage 2 disease. The average age was 59 years in the younger group and 74 years in the older group.
Older patients had a higher prevalence of cardiac, vascular, and pulmonary comorbidities and were more likely to have postoperative atrial arrhythmia and urinary retention.
However, there were no statistically significant differences in hospital length of stay (about 10 days in both groups), operative mortality (4.3% in the older group versus 3.8% in the younger group), or the incidence of postoperative grade 3 or higher complications (27.7% older versus 38.3% younger). Age-adjusted survival was 44.8% at 5 years among patients 70 years and older versus 39% among younger patients.
Comorbidity scores, clinically positive nodes, and clinical T3 tumors predicted worse survival on multivariate analysis, but age did not.
“Age itself doesn’t represent a contraindication to aggressive treatment. It is the patient’s comorbidities and functional status which are more important to predict the risk of complications after esophagectomy,” said Daniela Molena, MD, director of the esophageal surgery program at Memorial Sloan Kettering Cancer Center, New York, when asked for a comment.
The team noted that the results “reflect careful patient selection as well as thorough preoperative evaluation and preparation.” Patients with unstable or severe chronic heart disease, moderate to severe chronic liver disease, or severe chronic pulmonary disease were ineligible for surgery. Eligible patients had cardiac stress testing and were strongly encouraged to begin daily exercise. Nutritional deficiencies were addressed before surgery.
The Ochsner team is one of several in recent years that have pushed back on age limits for aggressive esophageal cancer treatment.
A British team, for example, reviewed 992 transthoracic esophagectomies, including 330 in patients 70 years or older, and found lower in-hospital mortality and pulmonary and cardiac morbidity for older patients than previously reported.
They concluded that “age should not be a discriminating factor when determining the treatment strategy for patients presenting with curative esophageal cancer.”
Even so, undertreatment remains “a big problem for elderly patients, and since the median age at diagnoses is 68 years, this is a problem for a large portion of patients with esophageal cancer,” Dr. Molena said.
“Patients can be cured of this disease” with aggressive treatment, but “unfortunately, patients often are not evaluated by a surgeon or referred to a high-volume center and are discouraged from undergoing surgery after an apparent good response to chemoradiation,” partly because esophagectomy has “unfairly gained a bad reputation over the years,” she said.
“There are clear data that outcomes of esophagectomy are very good at high volume centers with minimally invasive techniques and the ability to promptly identify and treat complications,” Dr. Molena said.
Overall, 52% of patients aged 70 years or older with stage II and III disease underwent NACR plus surgery at Ochsner, suggesting that “optimal, curative intent triple modality therapy [chemo, radiation, and esophagectomy] can be used successfully in a sizable segment of the elderly population,” the investigators said.
Treatment has changed significantly at Ochsner since the start of the review period in 2004, including a shift away from a fluorouracil and cisplatin doublet in favor of carboplatin and paclitaxel, which is less toxic, and greater use of minimally invasive surgery. The proportion of people 70 years or older undergoing triple modality treatment has been steadily increasing.
There was no outside funding. Investigator disclosures weren’t reported. Dr. Molena had no relevant disclosures.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
PET predicts response to endocrine therapy in ER+ breast cancer
Endocrine therapy is the standard of care for estrogen receptor–positive (ER+) breast cancer, but only about half of women respond. At present, there is no method for identifying the women who are likely – and also unlikely – to respond.
But a new approach looks to be useful. It involves a trial of estrogen followed by imaging that measures the function of estrogen receptors in the cancer cells.
This functional testing of estrogen receptors on breast cancer cells was perfectly accurate in predicting endocrine therapy response in 43 postmenopausal women with advanced ER+ disease, say researchers from Washington University, St. Louis, led by Farrokh Dehdashti, MD.
“There is an unmet clinical need to develop more precise predictive biomarkers. The results of this study are extremely promising,” they conclude.
The study was published online in Nature Communications.
For the study, the women were first infused with a radioactive progestin analog – 21-[18F]fluorofuranylnorprogesterone (FFNP) – that binds progesterone receptors. About 40 minutes later, they had a PET scan to assess its uptake, an indication of progesterone-receptor abundance.
The women were then given three 200-mg doses of estradiol over 24 hours.
The FFNP infusion and PET scan were repeated the next day.
Estradiol will cause cancer cells with functional estrogen receptors to produce more progesterone receptors, so increased uptake of the radioactive analog indicates functional estrogen receptors that will respond to endocrine therapy. If estrogen receptors are not functional, and therefore not amenable to endocrine therapy (ET), estradiol will not upregulate progesterone receptors.
The results proved the theory. FFNP uptake increased more than 6.7% in 28 subjects and a median of 25.4%. All 28 women responded to subsequent ET, including 15 partial responses and 13 women with stable disease at 6 months.
Median survival was not reached after a median follow up of 27.1 months.
Uptake increased no more than 6.7% in 15 subjects and, in fact, fell a median of 0.7% from baseline. None of these women responded to ET. The median survival was 22.6 months.
“We observed 100% agreement between the response to estrogen challenge and the response to hormone therapy. … This method should work for any therapy that depends on a functional estrogen receptor, and it could provide valuable information to oncologists deciding how best to treat their patients,” Dr. Dehdashti said in a press release.
A larger multicenter confirmation trial is in the works.
Oncology needs “to get away from empiric therapies and make therapy more individualized” to save patients from the morbidity and expense of ineffective treatment and wasting time when other options are available, Dr. Dehdashti told this news organization.
“It would be a good thing if we could identify endocrine-resistant patients,” said Charles Shapiro, MD, a professor and director of translational breast cancer research at Mount Sinai Hospital, New York.
However, he wondered “about the exportability to less resource-intensive community settings where most oncology care occurs. This technology, assuming the results are confirmed in a larger study, [needs] a cost-effectiveness analysis” vs. the empiric approach, Dr. Shapiro said in an interview.
The women taking part in this study were a median of 60 years old, and most had metastatic disease. PET imaging extended from the base of the skull to the upper thighs, with data derived from bone, lung, breast, and other tumor sites. ET options included aromatase inhibitors, fulvestrant, and tamoxifen in combination with other agents.
Almost three-quarters of the women had prior systemic treatment, most often a hormone therapy–based regimen. Prior treatment had no effect on FFNP uptake.
There were no adverse events with the radiotracer, but the estradiol made a few women nauseous, among other transient discomforts, the team reported.
The work was funded by the National Cancer Institute and Washington University, St. Louis. Dr. Shapiro and Dr. Dehdashti have disclosed no relevant financial relationships. Several investigators reported consulting fees and/or other ties to a number of companies, including Pfizer, Merck, Avid Radiopharmaceutical, and Radius Health.
A version of this article first appeared on Medscape.com.
Endocrine therapy is the standard of care for estrogen receptor–positive (ER+) breast cancer, but only about half of women respond. At present, there is no method for identifying the women who are likely – and also unlikely – to respond.
But a new approach looks to be useful. It involves a trial of estrogen followed by imaging that measures the function of estrogen receptors in the cancer cells.
This functional testing of estrogen receptors on breast cancer cells was perfectly accurate in predicting endocrine therapy response in 43 postmenopausal women with advanced ER+ disease, say researchers from Washington University, St. Louis, led by Farrokh Dehdashti, MD.
“There is an unmet clinical need to develop more precise predictive biomarkers. The results of this study are extremely promising,” they conclude.
The study was published online in Nature Communications.
For the study, the women were first infused with a radioactive progestin analog – 21-[18F]fluorofuranylnorprogesterone (FFNP) – that binds progesterone receptors. About 40 minutes later, they had a PET scan to assess its uptake, an indication of progesterone-receptor abundance.
The women were then given three 200-mg doses of estradiol over 24 hours.
The FFNP infusion and PET scan were repeated the next day.
Estradiol will cause cancer cells with functional estrogen receptors to produce more progesterone receptors, so increased uptake of the radioactive analog indicates functional estrogen receptors that will respond to endocrine therapy. If estrogen receptors are not functional, and therefore not amenable to endocrine therapy (ET), estradiol will not upregulate progesterone receptors.
The results proved the theory. FFNP uptake increased more than 6.7% in 28 subjects and a median of 25.4%. All 28 women responded to subsequent ET, including 15 partial responses and 13 women with stable disease at 6 months.
Median survival was not reached after a median follow up of 27.1 months.
Uptake increased no more than 6.7% in 15 subjects and, in fact, fell a median of 0.7% from baseline. None of these women responded to ET. The median survival was 22.6 months.
“We observed 100% agreement between the response to estrogen challenge and the response to hormone therapy. … This method should work for any therapy that depends on a functional estrogen receptor, and it could provide valuable information to oncologists deciding how best to treat their patients,” Dr. Dehdashti said in a press release.
A larger multicenter confirmation trial is in the works.
Oncology needs “to get away from empiric therapies and make therapy more individualized” to save patients from the morbidity and expense of ineffective treatment and wasting time when other options are available, Dr. Dehdashti told this news organization.
“It would be a good thing if we could identify endocrine-resistant patients,” said Charles Shapiro, MD, a professor and director of translational breast cancer research at Mount Sinai Hospital, New York.
However, he wondered “about the exportability to less resource-intensive community settings where most oncology care occurs. This technology, assuming the results are confirmed in a larger study, [needs] a cost-effectiveness analysis” vs. the empiric approach, Dr. Shapiro said in an interview.
The women taking part in this study were a median of 60 years old, and most had metastatic disease. PET imaging extended from the base of the skull to the upper thighs, with data derived from bone, lung, breast, and other tumor sites. ET options included aromatase inhibitors, fulvestrant, and tamoxifen in combination with other agents.
Almost three-quarters of the women had prior systemic treatment, most often a hormone therapy–based regimen. Prior treatment had no effect on FFNP uptake.
There were no adverse events with the radiotracer, but the estradiol made a few women nauseous, among other transient discomforts, the team reported.
The work was funded by the National Cancer Institute and Washington University, St. Louis. Dr. Shapiro and Dr. Dehdashti have disclosed no relevant financial relationships. Several investigators reported consulting fees and/or other ties to a number of companies, including Pfizer, Merck, Avid Radiopharmaceutical, and Radius Health.
A version of this article first appeared on Medscape.com.
Endocrine therapy is the standard of care for estrogen receptor–positive (ER+) breast cancer, but only about half of women respond. At present, there is no method for identifying the women who are likely – and also unlikely – to respond.
But a new approach looks to be useful. It involves a trial of estrogen followed by imaging that measures the function of estrogen receptors in the cancer cells.
This functional testing of estrogen receptors on breast cancer cells was perfectly accurate in predicting endocrine therapy response in 43 postmenopausal women with advanced ER+ disease, say researchers from Washington University, St. Louis, led by Farrokh Dehdashti, MD.
“There is an unmet clinical need to develop more precise predictive biomarkers. The results of this study are extremely promising,” they conclude.
The study was published online in Nature Communications.
For the study, the women were first infused with a radioactive progestin analog – 21-[18F]fluorofuranylnorprogesterone (FFNP) – that binds progesterone receptors. About 40 minutes later, they had a PET scan to assess its uptake, an indication of progesterone-receptor abundance.
The women were then given three 200-mg doses of estradiol over 24 hours.
The FFNP infusion and PET scan were repeated the next day.
Estradiol will cause cancer cells with functional estrogen receptors to produce more progesterone receptors, so increased uptake of the radioactive analog indicates functional estrogen receptors that will respond to endocrine therapy. If estrogen receptors are not functional, and therefore not amenable to endocrine therapy (ET), estradiol will not upregulate progesterone receptors.
The results proved the theory. FFNP uptake increased more than 6.7% in 28 subjects and a median of 25.4%. All 28 women responded to subsequent ET, including 15 partial responses and 13 women with stable disease at 6 months.
Median survival was not reached after a median follow up of 27.1 months.
Uptake increased no more than 6.7% in 15 subjects and, in fact, fell a median of 0.7% from baseline. None of these women responded to ET. The median survival was 22.6 months.
“We observed 100% agreement between the response to estrogen challenge and the response to hormone therapy. … This method should work for any therapy that depends on a functional estrogen receptor, and it could provide valuable information to oncologists deciding how best to treat their patients,” Dr. Dehdashti said in a press release.
A larger multicenter confirmation trial is in the works.
Oncology needs “to get away from empiric therapies and make therapy more individualized” to save patients from the morbidity and expense of ineffective treatment and wasting time when other options are available, Dr. Dehdashti told this news organization.
“It would be a good thing if we could identify endocrine-resistant patients,” said Charles Shapiro, MD, a professor and director of translational breast cancer research at Mount Sinai Hospital, New York.
However, he wondered “about the exportability to less resource-intensive community settings where most oncology care occurs. This technology, assuming the results are confirmed in a larger study, [needs] a cost-effectiveness analysis” vs. the empiric approach, Dr. Shapiro said in an interview.
The women taking part in this study were a median of 60 years old, and most had metastatic disease. PET imaging extended from the base of the skull to the upper thighs, with data derived from bone, lung, breast, and other tumor sites. ET options included aromatase inhibitors, fulvestrant, and tamoxifen in combination with other agents.
Almost three-quarters of the women had prior systemic treatment, most often a hormone therapy–based regimen. Prior treatment had no effect on FFNP uptake.
There were no adverse events with the radiotracer, but the estradiol made a few women nauseous, among other transient discomforts, the team reported.
The work was funded by the National Cancer Institute and Washington University, St. Louis. Dr. Shapiro and Dr. Dehdashti have disclosed no relevant financial relationships. Several investigators reported consulting fees and/or other ties to a number of companies, including Pfizer, Merck, Avid Radiopharmaceutical, and Radius Health.
A version of this article first appeared on Medscape.com.