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Image-guided superficial radiation as first-line in skin cancer?
The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.
Key takeaway
- Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.
Why this matters
- IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
- The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
- IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
- Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.
Study design
- The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
- Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
- Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.
Key results
- Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
- At a 5-year follow-up, local control was 99.4%.
- Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
- The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
- The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
- The results compare favorably with Mohs surgery.
Limitations
- No study limitations were noted.
Disclosures
- No funding source was reported.
- Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.
This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.
A version of this article first appeared on Medscape.com.
The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.
Key takeaway
- Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.
Why this matters
- IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
- The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
- IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
- Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.
Study design
- The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
- Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
- Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.
Key results
- Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
- At a 5-year follow-up, local control was 99.4%.
- Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
- The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
- The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
- The results compare favorably with Mohs surgery.
Limitations
- No study limitations were noted.
Disclosures
- No funding source was reported.
- Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.
This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.
A version of this article first appeared on Medscape.com.
The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.
Key takeaway
- Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.
Why this matters
- IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
- The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
- IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
- Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.
Study design
- The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
- Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
- Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.
Key results
- Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
- At a 5-year follow-up, local control was 99.4%.
- Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
- The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
- The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
- The results compare favorably with Mohs surgery.
Limitations
- No study limitations were noted.
Disclosures
- No funding source was reported.
- Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.
This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.
A version of this article first appeared on Medscape.com.
Despite benefits, extended-interval pembro uptake remains low
In April 2020, the Food and Drug Administration approved extended dosing for standalone pembrolizumab – 400 mg every 6 weeks instead of the standard dosing of 200 mg every 3 weeks. The shift came, in part, to reduce patient health care encounters during the early days of the COVID-19 pandemic, but also because fewer infusions save patients time and out-of-pocket costs and reduce the burden on the health care system.
The FDA deemed this move safe after pharmacologic studies and a small melanoma study found that responses and adverse events were equivalent in comparison with standard dosing.
Given the benefits, one would expect “brisk adoption” of extended-interval dosing, Garth Strohbehn, MD, an oncologist at the VA Medical Center in Ann Arbor, Mich., and colleagues wrote in a recent report in JAMA Oncology.
However, when the team reviewed data on 835 veterans from the Veterans Health Administration who began taking single-agent pembrolizumab between April 1, 2020, and July 1, 2021, only about one-third received extended-interval dosing.
Between April and January 2021, use of extended-interval dosing rose steadily to about 35% of patients but then hovered in that range through August 2021.
Among the patients, age, sex, Charlson comorbidity index, and pembrolizumab indications were well balanced between the standard-dosing and the extended-interval dosing groups.
Notably, Dr. Strohbehn and colleagues also found no difference in time-to-treatment discontinuation between patients receiving extended dosing in comparison with patients receiving standard dosing, which is “a real-world measure of clinical effectiveness,” the team said.
And there was no difference in immune-related side effects between the two regimens, as assessed by incident levothyroxine and prednisone prescriptions.
The real-world near equivalence of extended and standard dosing intervals that was demonstrated in the study is “reassuring” and helps make the case for considering it “as a best practice” for single-agent pembrolizumab, the investigators wrote.
Dr. Strohbehn remained somewhat puzzled by the low uptake of the extended-dosing option.
“I was frankly surprised by the small number of patients who received the extended-interval regimen,” Dr. Strohbehn said in an interview.
“Admittedly, there are patients who would prefer to receive standard-interval therapy, and that preference should of course be accommodated whenever possible, but in my experience, those numbers are small,” at least in the VA system, he noted.
In addition, the authors noted, there is no direct financial incentive for more frequent dosing in the VA system.
It’s possible that low uptake could stem from clinicians’ doubts about switching to an extended-interval dose, given that the FDA’s approval was based largely on a study of 44 patients with melanoma in a single-arm trial.
If that is indeed the case, the new findings – which represent the first health system–level, real-world comparative effectiveness data for standard vs. extended-interval pembrolizumab – should help address these concerns, the team said.
“This observational dataset lends further credence to [the dosing] regimens being clinically equivalent,” said Zachery Reichert, MD, PhD, a urologic oncologist at the University of Michigan, Ann Arbor, who was not involved in the study.
To address the issue, Dr. Strohbehn and his team suggested “clinical guideline promotion to overcome some of the barriers to the adoption of extended-interval pembrolizumab.”
Dr. Riechert suggested further validation of equivalent outcomes for the two regimens, more advocacy to encourage patients to ask about the 6-week option, as well as incentives from insurers to adopt it.
Dr. Strohbehn added that the situation highlights a broader issue in oncology, namely that many drugs “end up on the market with dosing regimens that haven’t necessarily been optimized.”
Across the world, investigators are conducting clinical trials “to identify the minimum dosages, frequencies, and durations patients need in order to achieve their best outcome,” Dr. Strohbehn said. In oncology, much of this effort is being led by Project Optimus, from the FDA’s Oncology Center of Excellence, he said.
The study was funded by the VA National Oncology Program. Dr. Reichert and Dr. Strohbehn have disclosed no relevant financial relationships. One investigator has received grants from Novartis, Bristol-Myers Squibb, Regeneron, and Genentech.
A version of this article first appeared on Medscape.com.
In April 2020, the Food and Drug Administration approved extended dosing for standalone pembrolizumab – 400 mg every 6 weeks instead of the standard dosing of 200 mg every 3 weeks. The shift came, in part, to reduce patient health care encounters during the early days of the COVID-19 pandemic, but also because fewer infusions save patients time and out-of-pocket costs and reduce the burden on the health care system.
The FDA deemed this move safe after pharmacologic studies and a small melanoma study found that responses and adverse events were equivalent in comparison with standard dosing.
Given the benefits, one would expect “brisk adoption” of extended-interval dosing, Garth Strohbehn, MD, an oncologist at the VA Medical Center in Ann Arbor, Mich., and colleagues wrote in a recent report in JAMA Oncology.
However, when the team reviewed data on 835 veterans from the Veterans Health Administration who began taking single-agent pembrolizumab between April 1, 2020, and July 1, 2021, only about one-third received extended-interval dosing.
Between April and January 2021, use of extended-interval dosing rose steadily to about 35% of patients but then hovered in that range through August 2021.
Among the patients, age, sex, Charlson comorbidity index, and pembrolizumab indications were well balanced between the standard-dosing and the extended-interval dosing groups.
Notably, Dr. Strohbehn and colleagues also found no difference in time-to-treatment discontinuation between patients receiving extended dosing in comparison with patients receiving standard dosing, which is “a real-world measure of clinical effectiveness,” the team said.
And there was no difference in immune-related side effects between the two regimens, as assessed by incident levothyroxine and prednisone prescriptions.
The real-world near equivalence of extended and standard dosing intervals that was demonstrated in the study is “reassuring” and helps make the case for considering it “as a best practice” for single-agent pembrolizumab, the investigators wrote.
Dr. Strohbehn remained somewhat puzzled by the low uptake of the extended-dosing option.
“I was frankly surprised by the small number of patients who received the extended-interval regimen,” Dr. Strohbehn said in an interview.
“Admittedly, there are patients who would prefer to receive standard-interval therapy, and that preference should of course be accommodated whenever possible, but in my experience, those numbers are small,” at least in the VA system, he noted.
In addition, the authors noted, there is no direct financial incentive for more frequent dosing in the VA system.
It’s possible that low uptake could stem from clinicians’ doubts about switching to an extended-interval dose, given that the FDA’s approval was based largely on a study of 44 patients with melanoma in a single-arm trial.
If that is indeed the case, the new findings – which represent the first health system–level, real-world comparative effectiveness data for standard vs. extended-interval pembrolizumab – should help address these concerns, the team said.
“This observational dataset lends further credence to [the dosing] regimens being clinically equivalent,” said Zachery Reichert, MD, PhD, a urologic oncologist at the University of Michigan, Ann Arbor, who was not involved in the study.
To address the issue, Dr. Strohbehn and his team suggested “clinical guideline promotion to overcome some of the barriers to the adoption of extended-interval pembrolizumab.”
Dr. Riechert suggested further validation of equivalent outcomes for the two regimens, more advocacy to encourage patients to ask about the 6-week option, as well as incentives from insurers to adopt it.
Dr. Strohbehn added that the situation highlights a broader issue in oncology, namely that many drugs “end up on the market with dosing regimens that haven’t necessarily been optimized.”
Across the world, investigators are conducting clinical trials “to identify the minimum dosages, frequencies, and durations patients need in order to achieve their best outcome,” Dr. Strohbehn said. In oncology, much of this effort is being led by Project Optimus, from the FDA’s Oncology Center of Excellence, he said.
The study was funded by the VA National Oncology Program. Dr. Reichert and Dr. Strohbehn have disclosed no relevant financial relationships. One investigator has received grants from Novartis, Bristol-Myers Squibb, Regeneron, and Genentech.
A version of this article first appeared on Medscape.com.
In April 2020, the Food and Drug Administration approved extended dosing for standalone pembrolizumab – 400 mg every 6 weeks instead of the standard dosing of 200 mg every 3 weeks. The shift came, in part, to reduce patient health care encounters during the early days of the COVID-19 pandemic, but also because fewer infusions save patients time and out-of-pocket costs and reduce the burden on the health care system.
The FDA deemed this move safe after pharmacologic studies and a small melanoma study found that responses and adverse events were equivalent in comparison with standard dosing.
Given the benefits, one would expect “brisk adoption” of extended-interval dosing, Garth Strohbehn, MD, an oncologist at the VA Medical Center in Ann Arbor, Mich., and colleagues wrote in a recent report in JAMA Oncology.
However, when the team reviewed data on 835 veterans from the Veterans Health Administration who began taking single-agent pembrolizumab between April 1, 2020, and July 1, 2021, only about one-third received extended-interval dosing.
Between April and January 2021, use of extended-interval dosing rose steadily to about 35% of patients but then hovered in that range through August 2021.
Among the patients, age, sex, Charlson comorbidity index, and pembrolizumab indications were well balanced between the standard-dosing and the extended-interval dosing groups.
Notably, Dr. Strohbehn and colleagues also found no difference in time-to-treatment discontinuation between patients receiving extended dosing in comparison with patients receiving standard dosing, which is “a real-world measure of clinical effectiveness,” the team said.
And there was no difference in immune-related side effects between the two regimens, as assessed by incident levothyroxine and prednisone prescriptions.
The real-world near equivalence of extended and standard dosing intervals that was demonstrated in the study is “reassuring” and helps make the case for considering it “as a best practice” for single-agent pembrolizumab, the investigators wrote.
Dr. Strohbehn remained somewhat puzzled by the low uptake of the extended-dosing option.
“I was frankly surprised by the small number of patients who received the extended-interval regimen,” Dr. Strohbehn said in an interview.
“Admittedly, there are patients who would prefer to receive standard-interval therapy, and that preference should of course be accommodated whenever possible, but in my experience, those numbers are small,” at least in the VA system, he noted.
In addition, the authors noted, there is no direct financial incentive for more frequent dosing in the VA system.
It’s possible that low uptake could stem from clinicians’ doubts about switching to an extended-interval dose, given that the FDA’s approval was based largely on a study of 44 patients with melanoma in a single-arm trial.
If that is indeed the case, the new findings – which represent the first health system–level, real-world comparative effectiveness data for standard vs. extended-interval pembrolizumab – should help address these concerns, the team said.
“This observational dataset lends further credence to [the dosing] regimens being clinically equivalent,” said Zachery Reichert, MD, PhD, a urologic oncologist at the University of Michigan, Ann Arbor, who was not involved in the study.
To address the issue, Dr. Strohbehn and his team suggested “clinical guideline promotion to overcome some of the barriers to the adoption of extended-interval pembrolizumab.”
Dr. Riechert suggested further validation of equivalent outcomes for the two regimens, more advocacy to encourage patients to ask about the 6-week option, as well as incentives from insurers to adopt it.
Dr. Strohbehn added that the situation highlights a broader issue in oncology, namely that many drugs “end up on the market with dosing regimens that haven’t necessarily been optimized.”
Across the world, investigators are conducting clinical trials “to identify the minimum dosages, frequencies, and durations patients need in order to achieve their best outcome,” Dr. Strohbehn said. In oncology, much of this effort is being led by Project Optimus, from the FDA’s Oncology Center of Excellence, he said.
The study was funded by the VA National Oncology Program. Dr. Reichert and Dr. Strohbehn have disclosed no relevant financial relationships. One investigator has received grants from Novartis, Bristol-Myers Squibb, Regeneron, and Genentech.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Metformin bombs in breast cancer in landmark trial
Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.
These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.
Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.
These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.
The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.
However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.
The study was published online in JAMA.
Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.
Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.
Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).
Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).
However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).
The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.
This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.
Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).
The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.
A version of this article first appeared on Medscape.com.
Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.
These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.
Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.
These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.
The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.
However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.
The study was published online in JAMA.
Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.
Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.
Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).
Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).
However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).
The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.
This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.
Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).
The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.
A version of this article first appeared on Medscape.com.
Metformin, a common option for patients with type 2 diabetes, had previously been shown in observational studies to be associated with improved survival of cancer patients. Those studies mostly involved older patients with cancer who also had diabetes.
These findings have led to trials of the use of metformin for patients with cancer who do not have diabetes, but two lung cancer trials found no effect on survival.
Now this latest trial in breast cancer, which included 3,649 patients with hormone receptor–positive or –negative disease – who did not have diabetes – also found that metformin had no effect on survival.
These results “tell us that metformin is not effective against the most common types of breast cancer and any off-label use [of] this drug for the treatment of these common types of breast cancer should be stopped,” lead investigator and medical oncologist Pamela Goodwin, MD, a breast cancer researcher at the Lunenfeld-Tanenbaum Research Institute in Toronto, said in a press release.
The negative results “underscore the need for well-conducted randomized trials” before observational studies are put into practice, Dr. Goodwin and her team said.
However, the investigators cautioned against extrapolating their results to patients with diabetes, noting that “because metformin is effective in type 2 diabetes, the results ... should not affect the use of metformin” in breast cancer patients who have diabetes.
The study was published online in JAMA.
Patients were enrolled from 2010 to 2013 while undergoing adjuvant treatment – chemotherapy, radiotherapy, hormone therapy, and/or others – following complete resection of T1-3, N0-3 tumors. They were almost exclusively women (mean age, 52.4 years), and almost 90% were non-Hispanic White. They were primarily from the United States and Canada, with some patients from the United Kingdom and Switzerland.
Patients were randomly assigned equally to receive either metformin 850 mg twice daily or placebo for 5 years. Median follow-up was about 8 years.
Among 2,533 patients with estrogen receptor– and/or progesterone receptor–positive disease, the incidence of invasive disease–free survival events was 2.78 per 100 patient-years in the metformin group, vs. 2.74 per 100 patient-years in the placebo arm (hazard ratio [HR], 1.01, P = .93). There were 1.46 deaths per 100 patient-years with metformin, vs. 1.32 with placebo (HR, 1.10, P = .47).
Metformin was stopped early at about 3 years for the 1,116 hormone receptor–negative patients after futility was declared on interim analysis. The incidence of invasive disease–free survival events was 3.58 with metformin, vs. 3.60 with placebo per 100 patient-years (HR, 1.01, P = .92). There were 1.91 deaths per 100 patient-years in the metformin arm, vs. 2.15 in the group that received placebo (HR, 0.89, P = .46).
However, the findings were different and suggested a signal among the small subset of patients (17% of the total) who had HER2-positive disease. There were 1.93 disease-free survival events with metformin per 100 patient-years, vs. 3.05 events with placebo (HR, 0.64, P = .03), and 0.78 deaths in the metformin arm, vs. 1.43 deaths per 100 patient-years in the placebo arm (HR, 0.54, P = .04).
The benefit seen in this HER2-postive subgroup was limited to patients with any C allele of the rs11212617 single-nucleotide variant.
This was an exploratory analysis, so the results need to be confirmed in a randomized trial, but it’s possible that metformin “could provide an additional treatment option for HER2-positive breast cancer,” Dr. Goodwin said.
Grade 3 or higher adverse events were more common with metformin (21.5% vs. 17.5%). The most common such events were hypertension (2.4% vs. 1.9%), irregular menses (1.5% vs. 1.4%), and diarrhea (1.9% vs. 0.8%).
The study was conducted by the Canadian Cancer Trials Group and was funded by the Canadian Cancer Society, the National Cancer Institute, and others. Dr. Goodwin has disclosed no relevant financial relationships. Several coauthors reported ties to Pfizer, Eli Lilly, Roche, and a number of other companies. One coauthor is an AstraZeneca employee.
A version of this article first appeared on Medscape.com.
‘Unprecedented crisis’: Hodgkin drug shortage persists
The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.
In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.
“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.
Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.
Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.
In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.
“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.
According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
Finding a substitute
In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.
The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.
The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?
For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.
The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.
For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.
Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.
For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.
The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).
For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).
For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.
Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”
To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.
For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.
Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.
The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.
No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.
In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.
“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.
Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.
Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.
In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.
“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.
According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
Finding a substitute
In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.
The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.
The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?
For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.
The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.
For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.
Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.
For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.
The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).
For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).
For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.
Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”
To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.
For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.
Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.
The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.
No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The persistent shortage of dacarbazine has led to an “acute and unprecedented crisis” in the treatment of patients with advanced classical Hodgkin lymphoma, experts say.
In a recent review, oncologists scoured decades of data to find the best alternatives for a range of scenarios. For fit adults younger than 60, the group recommends the seven-drug regimen BEACOPP – bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.
“Among all available regimens,” BEACOPP has “the most robust evidence” as a substitute for the four-drug standard ABVD, which includes doxorubicin, bleomycin, vinblastine, and dacarbazine, Pallawi Torka, MD, a hematologic oncologist at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and colleagues wrote in JCO Oncology Practice.
Last October, the Food and Drug Administration posted a notice about the dacarbazine shortage. According to the notice, the shortage occurred because of “manufacturing delays” and a “demand increase” affecting three companies supplying the U.S. market – Fresenius Kabi USA, Hikma Pharmaceuticals, and Teva. In an update issued May 4, the FDA said that 100-mg and 200-mg vials of the drug are now available from Fresenius. An update from April 8 said that 200-mg vials were available from Hikma.
Dacarbazine is hardly the only oncology drug to fall into short supply. Recent data show that shortages of oncology drugs have become more common in the United States in recent years, particularly generic drugs and those targeting hematologic malignancies.
In a recent national survey of oncology pharmacists, researchers found that almost two-thirds of institutions reported at least one drug shortage in the past month, representing a 34% increase between 2018 and 2019.
“This shortage of [dacarbazine] is not the first shortage of oncolytic drugs, and it certainly will not be the last,” Nicole Soriano, PharmD, hematology/oncology clinical pharmacist at Northwestern Memorial Hospital, Chicago, and colleagues wrote in a commentary accompanying the review.
According to Dr. Soriano and coauthors, “some studies have found that shortages are significant across many oncology disciplines and may lead to delays, changes in therapy, interference with clinical research, increased risk of medication errors, adverse outcomes, and increased costs.”
Finding a substitute
In the current analysis, Dr. Torka and her team conducted an exhaustive literature review in which they examined studies going back decades.
The authors highlight more than 10 alternative regimens for treating advanced classical Hodgkin lymphoma. They also provide a detailed treatment algorithm to help oncologists choose the best option for their individual patients as well as strategies for reintegrating ABVD into patient care should the supply of dacarbazine return to normal.
The first considerations: Can patients tolerate intensive chemotherapy, and are patients younger than 60?
For fit adults younger than 60, Dr. Torka and colleagues conclude that the BEACOPP regimen is the “preferred” option. In trials comparing ABVD to BEACOPP, both regimens demonstrated similar overall survival. And while BEACOPP may provide slightly “better disease control,” this approach may also come with greater toxicities in the short and long term, compared with ABVD, depending on the dosing strategy.
The authors also propose an alternative treatment strategy in case the supply of dacarbazine returns to normal mid-treatment. In this scenario, patients could receive an escalated BEACOPP regimen for two cycles and then undergo an interim positron-emission tomography scan. If the scan is negative and dacarbazine is available, the patient’s regimen could be deescalated to ABVD for four cycles without affecting disease control.
For pediatric patients, the authors recommend the ABVE-PC regimen, which includes six drugs – doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide. Data show that the 5-year overall survival among pediatric patients receiving ABVE-PC is 95%.
Stanford V-C – cyclophosphamide, doxorubicin hydrochloride, vinblastine, vincristine, bleomycin, etoposide, and prednisone – is another “acceptable approach” for pediatric patients, the authors noted.
For older patients with advanced disease or those unfit for intensive chemotherapy, the authors suggest evaluating them for fitness for anthracyclines to determine whether doxorubicin, in particular, is an option.
The researchers suggest one of the following three strategies for those who are doxorubicin-eligible: PVAG (prednisone, vinblastine, doxorubicin, and gemcitabine), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or EVA (etoposide, vinblastine, and doxorubicin).
For those unfit for anthracyclines, the options include COPP (cyclophosphamide, vincristine, procarbazine, and prednisone) or ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisone).
For frail patients who are ineligible for chemotherapy, the team recommends brentuximab alone or in combination with nivolumab.
Given the limited availability of dacarbazine, the authors say that the “current supply should be triaged to prioritize patients whose therapy cannot be changed and those without alternative acceptable options.”
To stretch available dacarbazine supplies as much as possible, the researchers and editorialists advocate for rounding doses within 5%-10% of the prescribed dose.
For example, Dr. Torka and colleagues explained, rounding a dose from 750 mg down to 700 mg would save one vial of dacarbazine.
Vial sharing and using drugs beyond their use dates by compounding with closed-system transfer devices are other strategies to preserve the existing supply of dacarbazine.
The goal of this review “is to give as many patients as possible the most optimal and efficacious therapy even with the strain on supply,” the editorialists wrote.
No funding for the study was reported. Dr. Torka is an adviser for Genentech, ADC Therapeutics, and TG Therapeutics. Dr. Soriano has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.