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Novel trastuzumab duocarmazine significantly improved survival in advanced HER2-positive breast cancer
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
Based on significant progression-free survival (PFS) benefits shown in the phase 3 TULIP trial, trastuzumab duocarmazine (SYD985) may provide a new treatment option among HER2-positive metastatic breast cancer patients, according to Cristina Saura, MD, head of the breast cancer program at Vall d’Hebron University Hospital, Barcelona. Dr. Saura presented the results of the TULIP trial (abstract LBA15) on Sept. 19 at the 2021 European Society for Medical Oncology Congress.
Trastuzumab duocarmazine is a novel HER2-targeting antibody-drug conjugate that consists of trastuzumab and a drug containing duocarmycin. Its three-way mechanism of action includes uptake of the antibody-drug conjugate by internalization and intracellular release of duocarmycin with two bystander effects: proteolytic cleavage and subsequent release of payload in the tumor microenvironment and diffusion of active payload to neighboring tumor cells.
While one physician described the results as encouraging, another said the treatment is not nearly ready for primetime.
“It is encouraging to observe clinically meaningful and potentially practice changing progression-free survival improvements in patients receiving treatment in the third line and beyond,” said Aditya Bardia, MD, Massachusetts General Hospital, Boston. “Several agents have been approved as treatments for HER2-positive metastatic breast cancer in recent years including T-DXd, neratinib, tucatinib, and margetuximab. Trastuzumab duocarmazine could eventually be another option.”
Fatima Cardoso, MD, director of the breast cancer unit at the Breast Cancer Research Foundation, New York, said: “At this time there is only a minor 2-month difference in progression-free survival and a nonsignificant overall difference. With the high incidence of ocular toxicity and four toxic deaths, we cannot recommend this drug for clinical practice, in my opinion.”
Two or more prior therapies for metastatic breast cancer
TULIP investigators enrolled 437 patients from 83 sites in 11 countries with HER2-positive locally advanced or metastatic breast cancer who had received two or more therapies for metastatic disease (treatment for brain metastases allowed). They were randomized 2:1 to trastuzumab duocarmazine (1.2 mg/kg every 21 days, 291 patients) or physician’s choice (146 patients) of one of three trastuzumab-containing combinations or lapatinib plus capecitabine. Treatment was continued until progression or unacceptable toxicity. The primary endpoint was centrally assessed PFS.
Longer PFS with trastuzumab duocarmazine
Median age was 57 years, and the median number of prior metastatic breast cancer regimens was 4.7. Centrally reviewed PFS was significantly longer in the trastuzumab duocarmazine group at 7.0 months versus 4.9 months for physicians choice treatment (hazard ratio, 0.64; 95% confidence interval, 0.49-0.84; P = .002). Subgroup analysis, also centrally reviewed, revealed numerical advantage for trastuzumab duocarmazine over physician’s choice across all categories (except for Eastern Cooperative Oncology Group status 2). Analysis of PFS by investigators showed a similar benefit for trastuzumab duocarmazine (6.9 months vs. 4.6 months; HR, 0.60; P < .001).
A first look at median overall survival showed a nonsignificant advantage for trastuzumab duocarmazine (20.4 months vs. 16.3 months (HR, 0.83; 95% CI, 0.62-1.09, P = .153). The overall response rate (partial or complete response) was similar between groups at 27.8% for trastuzumab duocarmazine and 29.5% for physician’s choice with reductions in target lesion measurement at 70.2% and 32.2% for trastuzumab duocarmazine and physician’s choice, respectively. The clinical benefit rates were 38.5% for trastuzumab duocarmazine and 32.2% for physician’s choice.
Ocular toxicity
Most patients had at least one treatment-related adverse event (96.5% SD985, 96.4% PC), and grade 3 or higher event rates were similar between groups (52.8% SYD985, 48.2% PC). The most frequently reported adverse events for trastuzumab duocarmazine were ocular toxicity, with conjunctivitis reported in 38.2%, and keratitis in 38.2%, with fatigue at 33.3%; for physician’s choice these were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease pneumonitis was reported for 7.6% (5.2% grade 1-2) of patients treated with trastuzumab duocarmazine, including two grade 5 events.
Eye toxicity led to discontinuations in 20.8% of trastuzumab duocarmazine patients, dose modifications in 22.9%, with dose modifications for interstitial lung disease/pneumonitis in 5.2% of trastuzumab duocarmazine patients. Six fatalities (2.1%) were reported in the trastuzumab duocarmazine group, with four attributed to treatment. Assessment of health-related quality of life showed no significant difference between groups.
Dr. Manich outlined risk mitigation strategies. Patients with prior keratitis were excluded and patients were given prophylactic lubricating eye drops and regular eye exams by ophthalmologists. Treatment was discontinued if grade 3 or higher keratitis developed, and was delayed if grade 3 conjunctivitis developed until it reduced to grade 2. Also, patients with prior pneumonitis were excluded and CT lung scans were evaluated for lung changes. New or worsening respiratory symptoms triggered a full diagnostic workup. Treatment was discontinued for grade 2 or higher pneumonitis and delayed until resolution for grade 1 pneumonitis.
TULIP was funded by Byondis. Dr. Saura disclosed numerous financial interests including support from AstraZeneca and Daiichi Sankyo.
FROM ESMO 2021
Treatment shows 'important improvements' in triple-negative breast cancer
But as a subanalysis of data from the randomized, phase 3 study showed, sacituzumab govitecan was associated with significantly better progression-free survival (PFS) and overall survival among patients without an initial TNBC diagnosis, with efficacy similar to that seen in the overall study population and in patients without known brain metastases, reported Joyce O’Shaughnessy, MD, at the 2021 European Society for Medical Oncology Congress. In her presentation (abstract 258P), Dr. O’Shaughnessy, who is an oncologist with the Texas Oncology–Baylor Charles A. Sammons Cancer Center in Dallas, said that it’s not uncommon to see acquired triple-negative breast cancer in patients who have hormone receptor–positive disease initially and then later on, develop triple-negative breast cancer.
“That is why at the time of metastatic diagnosis we always say that patients should have repeat receptor [testing], because it’s been well described that a subset of hormone receptor–positive breast can become triple negative under pressure from endocrine therapy,” said ASCENT coinvestigator Aditya Bardia, MD, MPH, Massachusetts General Hospital, Boston, in an interview
Coinvestigator Kevine Punie, MD, from University Hospitals Leuven (Belgium), said that “triple-negative breast cancer is a diagnosis of exclusion. This is a heterogenous disease where several biological subsets are merged.”
“It was important to perform this subgroup analysis to reassure us that the treatment effect we see from [sacituzumab govitecan] in the overall population is also observed in this specific subgroup of patients where biologically we’re treating a different disease,” he said in an interview.
Antibody-drug conjugate
Sacituzumab govitecan consists of an antibody targeted to the trophoblast antigen 2 cell surface receptor found on most breast cancer cells, plus the topoisomerase-1 inhibitor SN-38 as its toxic payload.
In the primary intent-to-treat (ITT) analysis of ASCENT, sacituzumab significantly prolonged PFS with a median of 4.8 versus 1.7 months for patients treated with the physician’s choice of either capecitabine, eribulin, vinorelbine, or gemcitabine. The difference translated into an HR for progression with the antibody-drug conjugate of 0.41 (P < .00001).
The subgroup analysis looked at outcomes for 70 patients randomized to sacituzumab govitecan and 78 randomized to single-agent chemotherapy who did not have an initial diagnosis of TNBC.
In all, 27% of patients in this subgroup in the sacituzumab arm and 29% in the chemotherapy arm had received a prior line of treatment with a CDK4/6 inhibitor.
At the time of data cutoff in March 2020, four patients (6%) in the sacituzumab arm remained on treatment versus no patient in the chemotherapy arm. The most common reason for treatment discontinuation was disease progression, which occurred in 84% and 72% of patients, respectively.
The median treatment duration was 5.1 months in the sacituzumab and 1.2 months in the chemotherapy arm. The median duration of follow-up was 10.6 and 6.1 months, respectively.
Progression-free survival, overall survival results
For all patients without an initial TNBC diagnosis, the median PFS was 4.6 months with sacituzumab versus 2.3 months with chemotherapy, which translated into a hazard ratio for progression of 0.48 (95% confidence interval, 0.32-0.72). The progression-free benefit with the antibody-drug conjugate was similar to that seen in the intent-to-treat population, as noted before, and among the overall population of patients in the study with no known brain metastases (HR, 5.6 vs. 1.7, respectively; P < .001).
The objective response rates were 21% in the sacituzumab and 5% in the chemotherapy arm. Objective responses were not affected by the prior use of CDK 4/6 inhibitors.
Median overall survival in this subgroup was 12.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy (95% CI, 0.30-0.64).
The investigators reported that the safety profile was manageable in this subgroup of patients, with a low rate of treatment discontinuations because of adverse events (5%) and no treatment-related deaths with sacituzumab govitecan.
Health-related quality of life
In a separate poster (abstract 257P) presented at the meeting, the ASCENT investigators reported health-related quality of life results in the overall population.
The mean European Organization for the Research and Treatment of Cancer quality of life questionnaire subscale scores at baseline were similar between treatment arms.
For the major domains of global health status, physical and emotional functioning as well as lower symptomatic impact of fatigue, pain, dyspnea, and insomnia, sacituzumab govitecan showed “significantly and meaningfully greater improvement” than the physician’s choice of chemotherapy, the investigators found.
Of individual symptoms, only diarrhea was worse with the antibody-drug conjugate.
“These were important improvements,” Dr. Punie said, “because we saw improvements in the primary health-related quality of life domains such as global health status. We also saw that the time to clinically meaningful deterioration of quality of life domains were significantly longer for patients treated with [sacituzumab govitecan].”
“Patients who received sacituzumab govitecan had better health-related quality of life as compared to the control arm, and that’s a very important result, because in the metastatic setting our goal is twofold: We want to prolong survival, and we want patients to have improved quality of life,” Dr. Bardia said.
The Ascent trial is sponsored by Gilead Sciences. Dr. Punie disclosed relationships with multiple companies/organizations, not including Gilead. Dr. Bardia disclosed contracted research for Gilead and others, as well as other relationships.
But as a subanalysis of data from the randomized, phase 3 study showed, sacituzumab govitecan was associated with significantly better progression-free survival (PFS) and overall survival among patients without an initial TNBC diagnosis, with efficacy similar to that seen in the overall study population and in patients without known brain metastases, reported Joyce O’Shaughnessy, MD, at the 2021 European Society for Medical Oncology Congress. In her presentation (abstract 258P), Dr. O’Shaughnessy, who is an oncologist with the Texas Oncology–Baylor Charles A. Sammons Cancer Center in Dallas, said that it’s not uncommon to see acquired triple-negative breast cancer in patients who have hormone receptor–positive disease initially and then later on, develop triple-negative breast cancer.
“That is why at the time of metastatic diagnosis we always say that patients should have repeat receptor [testing], because it’s been well described that a subset of hormone receptor–positive breast can become triple negative under pressure from endocrine therapy,” said ASCENT coinvestigator Aditya Bardia, MD, MPH, Massachusetts General Hospital, Boston, in an interview
Coinvestigator Kevine Punie, MD, from University Hospitals Leuven (Belgium), said that “triple-negative breast cancer is a diagnosis of exclusion. This is a heterogenous disease where several biological subsets are merged.”
“It was important to perform this subgroup analysis to reassure us that the treatment effect we see from [sacituzumab govitecan] in the overall population is also observed in this specific subgroup of patients where biologically we’re treating a different disease,” he said in an interview.
Antibody-drug conjugate
Sacituzumab govitecan consists of an antibody targeted to the trophoblast antigen 2 cell surface receptor found on most breast cancer cells, plus the topoisomerase-1 inhibitor SN-38 as its toxic payload.
In the primary intent-to-treat (ITT) analysis of ASCENT, sacituzumab significantly prolonged PFS with a median of 4.8 versus 1.7 months for patients treated with the physician’s choice of either capecitabine, eribulin, vinorelbine, or gemcitabine. The difference translated into an HR for progression with the antibody-drug conjugate of 0.41 (P < .00001).
The subgroup analysis looked at outcomes for 70 patients randomized to sacituzumab govitecan and 78 randomized to single-agent chemotherapy who did not have an initial diagnosis of TNBC.
In all, 27% of patients in this subgroup in the sacituzumab arm and 29% in the chemotherapy arm had received a prior line of treatment with a CDK4/6 inhibitor.
At the time of data cutoff in March 2020, four patients (6%) in the sacituzumab arm remained on treatment versus no patient in the chemotherapy arm. The most common reason for treatment discontinuation was disease progression, which occurred in 84% and 72% of patients, respectively.
The median treatment duration was 5.1 months in the sacituzumab and 1.2 months in the chemotherapy arm. The median duration of follow-up was 10.6 and 6.1 months, respectively.
Progression-free survival, overall survival results
For all patients without an initial TNBC diagnosis, the median PFS was 4.6 months with sacituzumab versus 2.3 months with chemotherapy, which translated into a hazard ratio for progression of 0.48 (95% confidence interval, 0.32-0.72). The progression-free benefit with the antibody-drug conjugate was similar to that seen in the intent-to-treat population, as noted before, and among the overall population of patients in the study with no known brain metastases (HR, 5.6 vs. 1.7, respectively; P < .001).
The objective response rates were 21% in the sacituzumab and 5% in the chemotherapy arm. Objective responses were not affected by the prior use of CDK 4/6 inhibitors.
Median overall survival in this subgroup was 12.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy (95% CI, 0.30-0.64).
The investigators reported that the safety profile was manageable in this subgroup of patients, with a low rate of treatment discontinuations because of adverse events (5%) and no treatment-related deaths with sacituzumab govitecan.
Health-related quality of life
In a separate poster (abstract 257P) presented at the meeting, the ASCENT investigators reported health-related quality of life results in the overall population.
The mean European Organization for the Research and Treatment of Cancer quality of life questionnaire subscale scores at baseline were similar between treatment arms.
For the major domains of global health status, physical and emotional functioning as well as lower symptomatic impact of fatigue, pain, dyspnea, and insomnia, sacituzumab govitecan showed “significantly and meaningfully greater improvement” than the physician’s choice of chemotherapy, the investigators found.
Of individual symptoms, only diarrhea was worse with the antibody-drug conjugate.
“These were important improvements,” Dr. Punie said, “because we saw improvements in the primary health-related quality of life domains such as global health status. We also saw that the time to clinically meaningful deterioration of quality of life domains were significantly longer for patients treated with [sacituzumab govitecan].”
“Patients who received sacituzumab govitecan had better health-related quality of life as compared to the control arm, and that’s a very important result, because in the metastatic setting our goal is twofold: We want to prolong survival, and we want patients to have improved quality of life,” Dr. Bardia said.
The Ascent trial is sponsored by Gilead Sciences. Dr. Punie disclosed relationships with multiple companies/organizations, not including Gilead. Dr. Bardia disclosed contracted research for Gilead and others, as well as other relationships.
But as a subanalysis of data from the randomized, phase 3 study showed, sacituzumab govitecan was associated with significantly better progression-free survival (PFS) and overall survival among patients without an initial TNBC diagnosis, with efficacy similar to that seen in the overall study population and in patients without known brain metastases, reported Joyce O’Shaughnessy, MD, at the 2021 European Society for Medical Oncology Congress. In her presentation (abstract 258P), Dr. O’Shaughnessy, who is an oncologist with the Texas Oncology–Baylor Charles A. Sammons Cancer Center in Dallas, said that it’s not uncommon to see acquired triple-negative breast cancer in patients who have hormone receptor–positive disease initially and then later on, develop triple-negative breast cancer.
“That is why at the time of metastatic diagnosis we always say that patients should have repeat receptor [testing], because it’s been well described that a subset of hormone receptor–positive breast can become triple negative under pressure from endocrine therapy,” said ASCENT coinvestigator Aditya Bardia, MD, MPH, Massachusetts General Hospital, Boston, in an interview
Coinvestigator Kevine Punie, MD, from University Hospitals Leuven (Belgium), said that “triple-negative breast cancer is a diagnosis of exclusion. This is a heterogenous disease where several biological subsets are merged.”
“It was important to perform this subgroup analysis to reassure us that the treatment effect we see from [sacituzumab govitecan] in the overall population is also observed in this specific subgroup of patients where biologically we’re treating a different disease,” he said in an interview.
Antibody-drug conjugate
Sacituzumab govitecan consists of an antibody targeted to the trophoblast antigen 2 cell surface receptor found on most breast cancer cells, plus the topoisomerase-1 inhibitor SN-38 as its toxic payload.
In the primary intent-to-treat (ITT) analysis of ASCENT, sacituzumab significantly prolonged PFS with a median of 4.8 versus 1.7 months for patients treated with the physician’s choice of either capecitabine, eribulin, vinorelbine, or gemcitabine. The difference translated into an HR for progression with the antibody-drug conjugate of 0.41 (P < .00001).
The subgroup analysis looked at outcomes for 70 patients randomized to sacituzumab govitecan and 78 randomized to single-agent chemotherapy who did not have an initial diagnosis of TNBC.
In all, 27% of patients in this subgroup in the sacituzumab arm and 29% in the chemotherapy arm had received a prior line of treatment with a CDK4/6 inhibitor.
At the time of data cutoff in March 2020, four patients (6%) in the sacituzumab arm remained on treatment versus no patient in the chemotherapy arm. The most common reason for treatment discontinuation was disease progression, which occurred in 84% and 72% of patients, respectively.
The median treatment duration was 5.1 months in the sacituzumab and 1.2 months in the chemotherapy arm. The median duration of follow-up was 10.6 and 6.1 months, respectively.
Progression-free survival, overall survival results
For all patients without an initial TNBC diagnosis, the median PFS was 4.6 months with sacituzumab versus 2.3 months with chemotherapy, which translated into a hazard ratio for progression of 0.48 (95% confidence interval, 0.32-0.72). The progression-free benefit with the antibody-drug conjugate was similar to that seen in the intent-to-treat population, as noted before, and among the overall population of patients in the study with no known brain metastases (HR, 5.6 vs. 1.7, respectively; P < .001).
The objective response rates were 21% in the sacituzumab and 5% in the chemotherapy arm. Objective responses were not affected by the prior use of CDK 4/6 inhibitors.
Median overall survival in this subgroup was 12.4 months with the antibody-drug conjugate versus 6.7 months with chemotherapy (95% CI, 0.30-0.64).
The investigators reported that the safety profile was manageable in this subgroup of patients, with a low rate of treatment discontinuations because of adverse events (5%) and no treatment-related deaths with sacituzumab govitecan.
Health-related quality of life
In a separate poster (abstract 257P) presented at the meeting, the ASCENT investigators reported health-related quality of life results in the overall population.
The mean European Organization for the Research and Treatment of Cancer quality of life questionnaire subscale scores at baseline were similar between treatment arms.
For the major domains of global health status, physical and emotional functioning as well as lower symptomatic impact of fatigue, pain, dyspnea, and insomnia, sacituzumab govitecan showed “significantly and meaningfully greater improvement” than the physician’s choice of chemotherapy, the investigators found.
Of individual symptoms, only diarrhea was worse with the antibody-drug conjugate.
“These were important improvements,” Dr. Punie said, “because we saw improvements in the primary health-related quality of life domains such as global health status. We also saw that the time to clinically meaningful deterioration of quality of life domains were significantly longer for patients treated with [sacituzumab govitecan].”
“Patients who received sacituzumab govitecan had better health-related quality of life as compared to the control arm, and that’s a very important result, because in the metastatic setting our goal is twofold: We want to prolong survival, and we want patients to have improved quality of life,” Dr. Bardia said.
The Ascent trial is sponsored by Gilead Sciences. Dr. Punie disclosed relationships with multiple companies/organizations, not including Gilead. Dr. Bardia disclosed contracted research for Gilead and others, as well as other relationships.
FROM ESMO 2021
Better survival with extended letrozole in early-stage breast cancer
The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.
Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.
The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.
Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.
Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).
Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).
At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.
It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.
With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.
Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.
For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.
However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.
Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.
There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”
The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.
The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.
Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.
The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.
Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.
Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).
Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).
At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.
It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.
With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.
Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.
For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.
However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.
Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.
There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”
The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.
The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.
Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.
The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.
Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.
Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).
Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).
At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.
It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.
With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.
Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.
For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.
However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.
Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.
There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”
The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.
FROM THE LANCET ONCOLOGY
FDA okays new oral CGRP antagonist for migraine prevention
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
the manufacturer announced in a release.
The once-daily medication will be available in doses of 10 mg, 30 mg, and 60 mg.
“Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients,” coinvestigator Peter J. Goadsby, MD, PhD, DSc, neurologist and professor at the University of California, Los Angeles, and King’s College London, said in the release.
Approval was based partly on the findings from the phase 3 ADVANCE trial, in which patients with episodic migraine were randomly assigned to receive placebo or a 10-mg, 30-mg, or 60-mg daily dose of atogepant for 12 weeks.
As reported by this news organization, all three doses of atogepant reduced the number of mean monthly migraine days.
With this approval, neurologists will be able to choose from four monoclonal antibodies and two gepants for the preventive treatment of migraine.
“Having another gepant that can also be given preventively is a good idea, because one may be better than the other for a patient,” Alan M. Rapoport, MD, past president of the International Headache Society and founder and director emeritus of the New England Center for Headache, Stamford, Conn., told this news organization.
“Once we have a year or so of experience with atogepant, we’ll have a pretty good idea of which one works better preventively,” said Dr. Rapoport, who was not involved with the research.
Practice changing?
In the ADVANCE trial, there was a reduction of 3.69 migraine days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose. Placebo was associated with a reduction of 2.48 migraine days.
In addition, more than half of patients in each atogepant arm achieved a reduction in mean monthly migraine days of 50% or greater. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group. Approximately 29% patients who received placebo achieved this outcome.
The data indicated that atogepant has a favorable safety profile. The most common adverse events associated with treatment were constipation, nausea, and upper respiratory tract infection.
Dr. Rapoport, who is also a clinical professor of neurology at UCLA, noted that he was impressed with the efficacy.
“I’m not as impressed with the adverse events, but they’re not serious, and they don’t necessarily last,” he said.
Although being able to prescribe a single drug for acute and preventive treatment may be an advantage, it remains to be seen whether the tolerability and price of atogepant will be barriers for patients, Dr. Rapoport added.
How the approval will affect clinical practice is also unclear, he noted.
“If you’re going to start someone on a preventive, especially if it’s a woman of childbearing potential, you might just consider one of the two gepants. Doctors will decide once they see how they work,” said Dr. Rapoport.
Not a ‘breakthrough’ treatment
Also commenting ahead of the approval, Elizabeth W. Loder, MD, vice chair for academic affairs in the department of neurology at Brigham and Women’s Hospital, Boston, noted that the “safety of these CGRP medications in pregnancy is uncertain, and there are theoretical reasons to be concerned about it.”
Unlike injectable CGRP medications, atogepant is eliminated from the body relatively quickly after the patient stops taking it, said Dr. Loder, who is also professor of neurology at Harvard Medical School, Boston. However, atogepant may not otherwise differ greatly from other medications of its type.
“I don’t see a reason to think that one of these oral CGRP medicines is much more effective than another one,” said Dr. Loder.
“In my mind, as a clinician who will be prescribing these for patients, it will be cost and the ease of getting it covered that makes the difference,” she added.
These questions may raise concerns. “Those of us who treat patients who do not have private insurance find it very difficult to get these medications for them, even in situations where they have exhausted other alternatives,” said Dr. Loder.
Patients insured by Medicare or Medicaid “usually have no avenue to get some of these new, expensive treatments,” she said.
The approval of atogepant for acute and preventive treatment shows that the distinction between these indications may be artificial, Dr. Loder noted. The approval “will, I hope, help people think more flexibly about the way in which we use medications.”
It is a positive that atogepant has emerged as another option for preventive therapy, but the treatment cannot be considered a breakthrough, Dr. Loder added. The efficacy of atogepant, like that of other preventive treatments for migraine, is modest.
“It would be so nice if we could find things that were more effective than the treatments we currently have,” said Dr. Loder.
A version of this article first appeared on Medscape.com.
‘Locker room talk’ about death: Time for oncologists to stop
In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.
When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.
When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.
The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”
The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.
It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
Oncologists’ ‘locker room talk’
And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.
This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.
But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.
The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
Making time for reflection
But taking time to reflect can be therapeutic.
I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.
I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”
When I checked in with the hospice, the patient had died.
I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.
It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
Abandoning locker room talk
So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.
We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.
We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.
And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.
Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.
In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.
When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.
When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.
The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”
The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.
It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
Oncologists’ ‘locker room talk’
And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.
This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.
But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.
The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
Making time for reflection
But taking time to reflect can be therapeutic.
I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.
I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”
When I checked in with the hospice, the patient had died.
I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.
It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
Abandoning locker room talk
So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.
We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.
We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.
And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.
Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.
In a recent inpatient service block, I was seeing patients alongside a resident I had gotten to know well. We were consulted on a patient with metastatic head and neck cancer who had not sought care for over a year.
When the patient presented, his voice was raspy and he could not swallow. He had lost 40 pounds. In addition to his locally advanced disease, his lungs were riddled with metastatic lesions.
When we left the room, the resident and I went to speak to the patient’s primary team, and he began to relay our recommendations.
The first words out of his mouth were, “Well, it’s pretty clear he’s going to die.”
The statement took me aback. I wasn’t alarmed by the accuracy of what he had said. The patient was obviously not doing well, and he ended up dying soon after this visit.
It was more the abrupt manner in which the resident had spoken about death. The brusque phrasing felt atypical coming from the otherwise gentle-hearted trainee. He wasn’t referring to a faceless person. We had just seen the man a few minutes ago and heard his personal struggles. I tried to see if anyone else on the team was caught off guard, but everyone was taking notes or continuing to listen, seemingly undeterred.
Oncologists’ ‘locker room talk’
And now, with the COVID pandemic forcing most of our tumor boards to go virtual, I find this locker room talk comes even more readily; phrases like “this patient is going to die” are often passed around flippantly, as if saying so will help ease the tension. During these interactions, my colleagues and I rarely acknowledge the seriousness of what a patient death will do to their family and loved ones – or what losing a patient whom we’ve known for years may do to our own psyche.
This language can even creep into how we speak with patients. We are often taught to offer prognoses coldly, ensuring that patients have a clear sense of how long they have left and to help inform their treatment choices. And yet, this training does not necessarily align with what patients want and need. For instance, in a recent survey of patients with chronic obstructive pulmonary disease, patients consistently rated physicians poorly at discussing prognosis, what dying might be like, as well as spirituality and religion.
But at the same time, these matter-of-fact statements about death probably help protect us. Death is a routine, inevitable part of an oncologist’s life, and over time, oncology training and practice hardens us to it. During medical school, I remember that a patient dying would trigger immediate reflection, sadness, and conversation with our peers. Now, unless I know a patient well, I find myself rarely reflecting on the patient behind the facts. This evolution is natural for an oncologist: If you don’t develop a tough skin about death, you may become overwhelmed with the frequency of it.
The COVID pandemic has amped our hardness toward death into overdrive. Whether we are in the intensive care unit or simply viewing death rates during the most recent COVID Delta wave, many of us cope by disassociating a face from a name.
Making time for reflection
But taking time to reflect can be therapeutic.
I recently referred a patient with metastatic prostate cancer for a phase 1 trial at an outside institution. He was one of the first patients in my genitourinary malignancies clinic when I started as an attending. The patient had progressed through several lines of therapy and was being referred for an investigational phase 1 therapy. We had discussed hospice referral, and the patient was ready for it if this therapy didn’t work out.
I did not see or hear from the man while he was on the trial. A few months later, however, the principal investigator of the trial called me to let me know the patient had progressed through the agent, suffering from significant urinary obstruction, and he was on hospice. “Unfortunately,” the investigator told me, “he’s not going to live much longer.”
When I checked in with the hospice, the patient had died.
I was surprised again at how matter-of-fact the discussion of death had been. But I was even more surprised by my own reaction. Despite the relationship I had formed with the patient, I did not feel much when I heard he had died. I didn’t have time to process the news in the moment. It was time to move on to the next patient.
It was only later, when I called the patient’s family, that I allowed my emotions to flood in. I told his family how grateful I was to know him, how strong he’d been. The patient’s family and I talked about the human, not his passing. It felt good.
Abandoning locker room talk
So how do we change how we talk about death? I don’t think the answer is massive educational programs or passing responsibility for advance care planning onto palliative care specialists. The change needs to be driven by individual oncologists. We can call out discussions of death that make us uncomfortable, gently reminding each other that we’re talking about a human life.
We can learn from our palliative care colleagues; their conversations about death routinely include a patient’s support system and personal stories. Palliative care doctors always refer to the patient by name, which helps humanize the person behind the chart.
We can emphasize a feeling of hope, a sentiment that may also be therapeutic to our patients. Even when a patient is dying, there is always something to be done. We can comfort their family, explaining what brought us to this point and how sorry we are that this is happening. We can provide options for symptom control and help patients manage those symptoms.
And we can allow ourselves to talk about how much a death affects us. We can acknowledge how much it sucks that a patient is going to die, how challenging that will be to his/her family, and how we wish it could have ended differently.
Subtle changes like these will improve our own ability to process and discuss death and will ultimately lead to better relationships with our patients. But it starts with eliminating the “locker room talk” of how we discuss death.
Ravi B. Parikh, MD, MPP, is a medical oncologist and faculty member at the University of Pennsylvania and the Philadelphia VA Medical Center, an adjunct fellow at the Leonard Davis Institute of Health Economics, and senior clinical advisor at the Coalition to Transform Advanced Care (C-TAC). He has served as a director, officer, partner, employee, adviser, consultant, or trustee for GNS Healthcare, Nanology, and Cancer Study Group, and he has received research grant from Embedded Healthcare, Veterans Administration, PCF, National Palliative Care Research Center, and MUSC. A version of this article first appeared on Medscape.com.
Immunotherapy Experience in Nonagenarian Veterans with Cancer
Background
Immune checkpoint inhibitors [cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 receptor/ programmed death ligand-1 (PD1/ PD-L1)] have received broad FDA approval in most cancers. As clinical use of these agents proliferates, data for their efficacy and safety in elderly populations, particularly nonagenarians, is sparse [1]. Nonagenarians are commonly excluded from or underrepresented in clinical trials. This occurs despite the fact that the elderly embody the fastest growing portion of the population worldwide [2]. The purpose of this project was to describe the experience of treating veterans >/= 90 years of age with immune checkpoint inhibitors (IPI) for cancer.
Methods
We reviewed drug exposure in Nonagenarians who received IPI within the VA system nationwide between 2016-2017 using CAPRI. We identified 48 veterans and reviewed each patient’s treatment, duration of immunotherapy exposure, response, and toxicity to generate a global review on how those nonagenarians tolerated treatment. Demographic data of study participants and all endpoints have been analyzed using descriptive statistics.
Results
We obtained the record data for 48 veterans who received CPI in the VA health system between 2016 and 2017. Baseline characteristics revealed that the majority of patients (N=26) were ECOG 0-1 at the time of treatment initiation. The most commonly treated malignancies included melanoma (N=19) and NSCLC (N=15) with the majority of cancers being stage IV (N=42). The primary outcome measures are duration of therapy (average 12.2 cycles) and overall survival (average 1.59 years). The secondary outcome is adverse events, with a total rate of 27.1% and grade III/IV events occurring at a rate of 6.3%
Implications
These cases and data points illustrate that immunotherapy is being used in nonagenarians. With close monitoring of toxicities, nonagenarians with acceptable performance status can be treated with immunotherapy with their consent. Future aims will focus on the addition of more data points by expanding to include 2018.
References
1. Lewis JH, Kilgore ML, Goldman DP, Trimble EL, Kaplan R,Montello MJ, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21(7):1383–9. 2. Sgambato S, Casaluce F, Gridelli C. The role of checkpoint inhibitors immunotherapy in advanced non-small cell lung cancer in the elderly. Expert Opin Biol Ther. 2017;17(5):565-571.
Background
Immune checkpoint inhibitors [cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 receptor/ programmed death ligand-1 (PD1/ PD-L1)] have received broad FDA approval in most cancers. As clinical use of these agents proliferates, data for their efficacy and safety in elderly populations, particularly nonagenarians, is sparse [1]. Nonagenarians are commonly excluded from or underrepresented in clinical trials. This occurs despite the fact that the elderly embody the fastest growing portion of the population worldwide [2]. The purpose of this project was to describe the experience of treating veterans >/= 90 years of age with immune checkpoint inhibitors (IPI) for cancer.
Methods
We reviewed drug exposure in Nonagenarians who received IPI within the VA system nationwide between 2016-2017 using CAPRI. We identified 48 veterans and reviewed each patient’s treatment, duration of immunotherapy exposure, response, and toxicity to generate a global review on how those nonagenarians tolerated treatment. Demographic data of study participants and all endpoints have been analyzed using descriptive statistics.
Results
We obtained the record data for 48 veterans who received CPI in the VA health system between 2016 and 2017. Baseline characteristics revealed that the majority of patients (N=26) were ECOG 0-1 at the time of treatment initiation. The most commonly treated malignancies included melanoma (N=19) and NSCLC (N=15) with the majority of cancers being stage IV (N=42). The primary outcome measures are duration of therapy (average 12.2 cycles) and overall survival (average 1.59 years). The secondary outcome is adverse events, with a total rate of 27.1% and grade III/IV events occurring at a rate of 6.3%
Implications
These cases and data points illustrate that immunotherapy is being used in nonagenarians. With close monitoring of toxicities, nonagenarians with acceptable performance status can be treated with immunotherapy with their consent. Future aims will focus on the addition of more data points by expanding to include 2018.
References
1. Lewis JH, Kilgore ML, Goldman DP, Trimble EL, Kaplan R,Montello MJ, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21(7):1383–9. 2. Sgambato S, Casaluce F, Gridelli C. The role of checkpoint inhibitors immunotherapy in advanced non-small cell lung cancer in the elderly. Expert Opin Biol Ther. 2017;17(5):565-571.
Background
Immune checkpoint inhibitors [cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 receptor/ programmed death ligand-1 (PD1/ PD-L1)] have received broad FDA approval in most cancers. As clinical use of these agents proliferates, data for their efficacy and safety in elderly populations, particularly nonagenarians, is sparse [1]. Nonagenarians are commonly excluded from or underrepresented in clinical trials. This occurs despite the fact that the elderly embody the fastest growing portion of the population worldwide [2]. The purpose of this project was to describe the experience of treating veterans >/= 90 years of age with immune checkpoint inhibitors (IPI) for cancer.
Methods
We reviewed drug exposure in Nonagenarians who received IPI within the VA system nationwide between 2016-2017 using CAPRI. We identified 48 veterans and reviewed each patient’s treatment, duration of immunotherapy exposure, response, and toxicity to generate a global review on how those nonagenarians tolerated treatment. Demographic data of study participants and all endpoints have been analyzed using descriptive statistics.
Results
We obtained the record data for 48 veterans who received CPI in the VA health system between 2016 and 2017. Baseline characteristics revealed that the majority of patients (N=26) were ECOG 0-1 at the time of treatment initiation. The most commonly treated malignancies included melanoma (N=19) and NSCLC (N=15) with the majority of cancers being stage IV (N=42). The primary outcome measures are duration of therapy (average 12.2 cycles) and overall survival (average 1.59 years). The secondary outcome is adverse events, with a total rate of 27.1% and grade III/IV events occurring at a rate of 6.3%
Implications
These cases and data points illustrate that immunotherapy is being used in nonagenarians. With close monitoring of toxicities, nonagenarians with acceptable performance status can be treated with immunotherapy with their consent. Future aims will focus on the addition of more data points by expanding to include 2018.
References
1. Lewis JH, Kilgore ML, Goldman DP, Trimble EL, Kaplan R,Montello MJ, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21(7):1383–9. 2. Sgambato S, Casaluce F, Gridelli C. The role of checkpoint inhibitors immunotherapy in advanced non-small cell lung cancer in the elderly. Expert Opin Biol Ther. 2017;17(5):565-571.
Evaluation of the Impact of the VHA National Precision Oncology Program (NPOP) on Prior Authorization Adjudication of Targeted Anti-Cancer Agents
Purpose
To evaluate the impact of the VHA NPOP on prescribing and prior authorization approval of targeted anti-cancer therapies.
Background
Comprehensive genomic profiling (CGP) next-generation sequencing (NGS) panels have seen increased use to guide oncology therapeutic decision making. In-line with the White House Cancer Moonshot initiative, the VHA established the National Precision Oncology Program (NPOP) in July of 2016 to provide veterans with easier access to CGP and help match patients with commercially available targeted oncology therapies based on their tumor molecular profile.
Methods/Data Analysis
A retrospective review within the VHA was conducted on patients who underwent CGP testing through the VHA NPOP from July 2016 through December 2020. Prior authorization drug request (PADR) consults for targeted oncology therapies for which CGP is a companion diagnostic for use were queried and approval outcomes were determined. NPOP interfacility consult (IFC) data was queried and matched to PADR and prescription data to determine if the IFC therapy recommendation was accepted and prescribed. Descriptive statistics were used to describe patient demographics and characterize PADR and IFC outcomes.
Results
From July 2016 to December 2020, 16,312 tumor and blood samples from 130 unique VA medical centers representing 15,467 veterans were analyzed. Approximately 15% of veterans were prescribed targeted oncology therapies that required a PADR with a 95% approval rate. Targeted therapy recommendations with corresponding level of evidence was seen in 160 of 425 IFCs. Among 160 IFCs with targeted therapy recommendations, 75 had the recommendations accepted with two denied by PADR after local review. Recommended therapies were ultimately received by 72 patients as one patient did not have an active drug order.
Implications
Implementation of the VHA NPOP has increased access to CGP for more than 15,000 veterans. Availability of CGP results may have affected PADR approval outcomes of targeted therapies in approximately 15% of veterans. Approximately 50% of IFCs led to approval and subsequent prescribing of recommended therapies. Further analysis of these data and trends may help guide future prescribing practices and aid with development of clinical pathways involving molecularly targeted anti-cancer therapies.
Purpose
To evaluate the impact of the VHA NPOP on prescribing and prior authorization approval of targeted anti-cancer therapies.
Background
Comprehensive genomic profiling (CGP) next-generation sequencing (NGS) panels have seen increased use to guide oncology therapeutic decision making. In-line with the White House Cancer Moonshot initiative, the VHA established the National Precision Oncology Program (NPOP) in July of 2016 to provide veterans with easier access to CGP and help match patients with commercially available targeted oncology therapies based on their tumor molecular profile.
Methods/Data Analysis
A retrospective review within the VHA was conducted on patients who underwent CGP testing through the VHA NPOP from July 2016 through December 2020. Prior authorization drug request (PADR) consults for targeted oncology therapies for which CGP is a companion diagnostic for use were queried and approval outcomes were determined. NPOP interfacility consult (IFC) data was queried and matched to PADR and prescription data to determine if the IFC therapy recommendation was accepted and prescribed. Descriptive statistics were used to describe patient demographics and characterize PADR and IFC outcomes.
Results
From July 2016 to December 2020, 16,312 tumor and blood samples from 130 unique VA medical centers representing 15,467 veterans were analyzed. Approximately 15% of veterans were prescribed targeted oncology therapies that required a PADR with a 95% approval rate. Targeted therapy recommendations with corresponding level of evidence was seen in 160 of 425 IFCs. Among 160 IFCs with targeted therapy recommendations, 75 had the recommendations accepted with two denied by PADR after local review. Recommended therapies were ultimately received by 72 patients as one patient did not have an active drug order.
Implications
Implementation of the VHA NPOP has increased access to CGP for more than 15,000 veterans. Availability of CGP results may have affected PADR approval outcomes of targeted therapies in approximately 15% of veterans. Approximately 50% of IFCs led to approval and subsequent prescribing of recommended therapies. Further analysis of these data and trends may help guide future prescribing practices and aid with development of clinical pathways involving molecularly targeted anti-cancer therapies.
Purpose
To evaluate the impact of the VHA NPOP on prescribing and prior authorization approval of targeted anti-cancer therapies.
Background
Comprehensive genomic profiling (CGP) next-generation sequencing (NGS) panels have seen increased use to guide oncology therapeutic decision making. In-line with the White House Cancer Moonshot initiative, the VHA established the National Precision Oncology Program (NPOP) in July of 2016 to provide veterans with easier access to CGP and help match patients with commercially available targeted oncology therapies based on their tumor molecular profile.
Methods/Data Analysis
A retrospective review within the VHA was conducted on patients who underwent CGP testing through the VHA NPOP from July 2016 through December 2020. Prior authorization drug request (PADR) consults for targeted oncology therapies for which CGP is a companion diagnostic for use were queried and approval outcomes were determined. NPOP interfacility consult (IFC) data was queried and matched to PADR and prescription data to determine if the IFC therapy recommendation was accepted and prescribed. Descriptive statistics were used to describe patient demographics and characterize PADR and IFC outcomes.
Results
From July 2016 to December 2020, 16,312 tumor and blood samples from 130 unique VA medical centers representing 15,467 veterans were analyzed. Approximately 15% of veterans were prescribed targeted oncology therapies that required a PADR with a 95% approval rate. Targeted therapy recommendations with corresponding level of evidence was seen in 160 of 425 IFCs. Among 160 IFCs with targeted therapy recommendations, 75 had the recommendations accepted with two denied by PADR after local review. Recommended therapies were ultimately received by 72 patients as one patient did not have an active drug order.
Implications
Implementation of the VHA NPOP has increased access to CGP for more than 15,000 veterans. Availability of CGP results may have affected PADR approval outcomes of targeted therapies in approximately 15% of veterans. Approximately 50% of IFCs led to approval and subsequent prescribing of recommended therapies. Further analysis of these data and trends may help guide future prescribing practices and aid with development of clinical pathways involving molecularly targeted anti-cancer therapies.
Improving the Efficiency of Ordering Next Generation Sequencing During New Patient Triage: A Quality Improvement Project
Objective
To decrease the time to treatment by streamlining ordering of next generation sequencing (NGS) during new patient triage utilizing a centralized document of indications for testing.
Background
Use of NGS in management of patients with cancer is rapidly expanding. In 2017, over 75% of oncologists reported using NGS to guide treatment decisions (1). NGS testing is also now incorporated into 67% of NCCN guidelines (2). However, due to the wide variety and changing indications for NGS, integrating testing into routine clinical care can be challenging.
Results
A total of 118 new patients were seen at the SLC VA Oncology Clinic between 2020-2021 of which 21 met criteria for NGS testing at time of triage consult, 10 before and 11 after the intervention. Median time from triage to treatment initiation was 30 days (30-33) after the incorporation of the document into clinic workflow compared to 63 days (47-66). Median time from biopsy to NGS results was similar between pre- and post-intervention groups, 28 (25-49) vs 26 days (18.5-26.5).
Conclusion
Our centralized summary of NGS indications is easily updated and accessible to staff. To date, shorter times from triage to treatment have been seen after integrating this document into clinic workflow. As our sample size is small, further evaluation of this trend is required. However, our data suggests that additional improvement may be achieved through incorporating this document into the Pathology department’s workflow.
References
(1) Freedman A et al. Use of NGS sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States. JCO Precis Oncol. 2018;2:1-13. (2) Conway J et al. NGS and the clinical oncology workflow: data challenges, proposed solutions and a call to action. JCO Precis Oncol. 2019;3:1-10.
Objective
To decrease the time to treatment by streamlining ordering of next generation sequencing (NGS) during new patient triage utilizing a centralized document of indications for testing.
Background
Use of NGS in management of patients with cancer is rapidly expanding. In 2017, over 75% of oncologists reported using NGS to guide treatment decisions (1). NGS testing is also now incorporated into 67% of NCCN guidelines (2). However, due to the wide variety and changing indications for NGS, integrating testing into routine clinical care can be challenging.
Results
A total of 118 new patients were seen at the SLC VA Oncology Clinic between 2020-2021 of which 21 met criteria for NGS testing at time of triage consult, 10 before and 11 after the intervention. Median time from triage to treatment initiation was 30 days (30-33) after the incorporation of the document into clinic workflow compared to 63 days (47-66). Median time from biopsy to NGS results was similar between pre- and post-intervention groups, 28 (25-49) vs 26 days (18.5-26.5).
Conclusion
Our centralized summary of NGS indications is easily updated and accessible to staff. To date, shorter times from triage to treatment have been seen after integrating this document into clinic workflow. As our sample size is small, further evaluation of this trend is required. However, our data suggests that additional improvement may be achieved through incorporating this document into the Pathology department’s workflow.
References
(1) Freedman A et al. Use of NGS sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States. JCO Precis Oncol. 2018;2:1-13. (2) Conway J et al. NGS and the clinical oncology workflow: data challenges, proposed solutions and a call to action. JCO Precis Oncol. 2019;3:1-10.
Objective
To decrease the time to treatment by streamlining ordering of next generation sequencing (NGS) during new patient triage utilizing a centralized document of indications for testing.
Background
Use of NGS in management of patients with cancer is rapidly expanding. In 2017, over 75% of oncologists reported using NGS to guide treatment decisions (1). NGS testing is also now incorporated into 67% of NCCN guidelines (2). However, due to the wide variety and changing indications for NGS, integrating testing into routine clinical care can be challenging.
Results
A total of 118 new patients were seen at the SLC VA Oncology Clinic between 2020-2021 of which 21 met criteria for NGS testing at time of triage consult, 10 before and 11 after the intervention. Median time from triage to treatment initiation was 30 days (30-33) after the incorporation of the document into clinic workflow compared to 63 days (47-66). Median time from biopsy to NGS results was similar between pre- and post-intervention groups, 28 (25-49) vs 26 days (18.5-26.5).
Conclusion
Our centralized summary of NGS indications is easily updated and accessible to staff. To date, shorter times from triage to treatment have been seen after integrating this document into clinic workflow. As our sample size is small, further evaluation of this trend is required. However, our data suggests that additional improvement may be achieved through incorporating this document into the Pathology department’s workflow.
References
(1) Freedman A et al. Use of NGS sequencing tests to guide cancer treatment: results from a nationally representative survey of oncologists in the United States. JCO Precis Oncol. 2018;2:1-13. (2) Conway J et al. NGS and the clinical oncology workflow: data challenges, proposed solutions and a call to action. JCO Precis Oncol. 2019;3:1-10.
Successful Recruitment of VA Patients in Precision Medicine Research Through Passive Recruitment Efforts
Background
We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.
Methods
We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.
Results
From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.
Implications
The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.
Background
We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.
Methods
We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.
Results
From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.
Implications
The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.
Background
We sought to evaluate passive recruitment efforts of VA patients into a precision medicine research program. Access to clinical trials and other research opportunities is important to discovering new disease treatments and better ways to detect, diagnose, and reduce disease risk. The WISDOM (Women Informed to Screen Depending on Measures of risk) Study is a multi-site, pragmatic trial with webbased participation based at the University of California at San Francisco (UCSF) that aims to move breast cancer screening away from its current one-size-fitsall approach to one that is personalized based on each woman’s individual risk.
Methods
We created a hub and spoke recruitment model with the San Francisco VA Medical Center (SFVAMC) serving as the central hub of passive recruitment activities and eligible VA facilities that agreed to participate serving as the spoke recruitment sites. Eligible facilities had at least 3,000 women patients, VA clinical genetic services available, a site lead from the VA Women’s Health-Practice-Based Research Network, and mammography on site. Site participation involved permission for the research team to email eligible patients (women aged 40-74 without prior breast cancer diagnosis) about the WISDOM Study. We evaluated the effectiveness of the recruitment by assessing trends in enrollment and monitoring participation of VA patients in the WISDOM Study. Analysis: Pre/post frequencies of women consenting to participate in the WISDOM Study.
Results
From 5/24/2021 through 6/21/2021, we emailed 27,061 eligible VA patients from six participating VA facilities. Prior to the VA emailing, an average of 22 women per week consented to participating in the WISDOM Study and none were Veterans. After the first month of the VA emailing, an average of 186 women per week consented – a 7.5-fold increase. Additionally, during the first month of VA emailing, 81% of women registering with the WISDOM Study said they heard about the study from the VA.
Implications
The VA has recently approved of emailing as a method for recruiting research subjects. Our results demonstrate this is a feasible approach for precision medicine research, a growing area of research in VA and at academic affiliates.
COVID-19 vaccines in pregnancy may protect baby, too
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
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Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
FROM AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM