Breast Cancer

The fall 2017 approval by the US Food and Drug Administration (FDA) of abemaciclib made it the third cyclin-dependent kinase (CDK) inhibitor approved for the treatment of hormone receptor (HR)-positive breast cancer, and the first to receive an approved indication as monotherapy in that setting. Abemaciclib is a small-molecule inhibitor of the CDK4 and CDK6 proteins, which are key gatekeepers of the cell cycle and frequently dysregulated in HR-positive breast cancer. On the basis of the randomized, placebo-controlled, multicenter phase 3 MONARCH-2 trial, it was approved in combination with fulvestrant for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer who had progressed during endocrine therapy.¹

A total of 669 women aged 18 years and older, with any menopausal status, an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) or nonmeasurable bone-only disease, were enrolled. Patients had progressed during neoadjuvant or adjuvant endocrine therapy, within 12 months of adjuvant endocrine therapy, or during frontline endocrine treatment for metastatic disease.

Those who had received more than 1 endocrine therapy or any prior chemotherapy for metastatic breast cancer or prior treatment with everolimus or CDK4/6 inhibitors, as well as those with the presence of visceral crisis or evidence or history of central nervous system (CNS) metastases, were excluded from the study.

Patients were randomized 2:1 to receive 150 mg abemaciclib or placebo, both in combination with 500 mg fulvestrant. The initial dose of abemaciclib was 200 mg, but this was amended to 150mg after enrollment of the first 178 patients to alleviate diarrhea-related toxicity concerns. Randomization was stratified according to metastatic site (visceral, bone only, or other) and endocrine therapy resistance (primary or secondary).

Tumors were measured by computed tomography (CT) and magnetic-resonance imaging (MRI) according to RECIST-1.1 within 28 days before random assignment, every 8 weeks for the first year, every 12 weeks thereafter, and then within 2 weeks of clinical progression. Bone scintigraphy was also performed at baseline and then every 6th cycle starting with cycle 7. Hematologic and blood chemistry laboratory tests were performed centrally on days 1 and 15 of the first cycle and day 1 of all remaining cycles.

The primary endpoint was progression-free survival (PFS); median PFS was 16.4 months in the abemaciclib arm, compared with 9.3 months in the placebo arm in the intent-to-treat population (hazard ratio [HR], 0.553;P < .0000001), translating to a 45% reduction in the risk of disease progression or death with the combination. Objective response rate in the 2 groups among patients with measurable disease was 48.1% and 21.3%, respectively, which included a complete response rate of 3.5% in the abemaciclib arm. The median duration of response was not yet reached in the study group, compared with 25.6 months for placebo. Overall survival data were not yet mature.

The agency also approved abemaciclib as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. That approval was based on data from the single-arm MONARCH-1 trial of 132 patients who received 200 mg abemaciclib twice daily on a continuous schedule.²

Patients had adequate organ function, measurable disease per RECIST-1.1, and an ECOG performance status of 0 or 1. Patients must have progressed on or after previous endocrine therapy and have received prior treatment with at least 2 chemotherapy regimens, at least 1 of them, but no more than 2, having been administered in the metastatic setting. Exclusion criteria included prior receipt of a CDK inhibitor, major surgery within 14 days of the start of the study, and CNS metastases.

Tumor assessments were performed by CT or MRI according to RECIST-1.1 within the 4 weeks prior to the first dose of study drug and then subsequently at every other cycle. Responses were confirmed at least 4 weeks after the initial observation. The overall response rate was 19.7%, made up completely of partial responses. Median duration of response was 8.6 months, median PFS was 6 months and median OS was 17.7 months.
 

Adverse events

The most common adverse events experienced with the combination of abemaciclib and fulvestrant were neutropenia (23.6%) and diarrhea (13.4%). The rate of grade 4 neutropenia was higher in the combination arm (2.9% vs 0.4%) and there were 3 deaths with the combination that were linked to treatment-related AEs. In the monotherapy trial, abemaciclib treatment most commonly caused diarrhea (90.2%), fatigue (65.2%), nausea (64.4%), decreased appetite (45.5%), and abdominal pain (38.6%). Grade 3 diarrhea and fatigue occurred in 19.7% and 12.9% of patients, respectively. Serious AEs occurred in 24.2% of patients and AEs led to treatment discontinuation in 7.6% of patients.

Warnings and precautions

Abemaciclib is marketed as Verzenio by Eli Lilly and Company. Warnings and precautions relating to diarrhea, neutropenia, hepatotoxicity, venous thromboembolism (VTE), and embryofetal toxicity are detailed in the prescribing information. In the event of diarrhea, patients should be treated with antidiarrheal therapy and should increase oral fluids and notify their health care provider. Treatment should be interrupted for grade 3 or 4 diarrhea and then resumed at a lower dose upon return to grade 1.

To guard against neutropenia, complete blood counts should be performed prior to starting therapy, every 2 weeks for the first 2 months, monthly for the subsequent 2 months, and then as clinically indicated. Treatment should be interrupted or delayed or the dose reduced for grade 3 or 4 neutropenia and patients should report episodes of fever.

Liver function tests should be performed before starting abemaciclib, every 2 weeks for the first 2 months, monthly for the next 2 months, and then as clinically indicated. For patients who develop persistent or recurrent grade 2, 3 or 4 hepatic transaminase elevation, dose interruption, reduction, discontinuation, or delay should be considered.

Patients should be monitored for signs and symptoms of VTE and pulmonary embolism, and treated appropriately. Pregnant women should be advised of the potential risk to a fetus, and those of reproductive potential should be counselled on the importance of using effective contraception during treatment and for at least 3 weeks after the last dose.³

The fall 2017 approval by the US Food and Drug Administration (FDA) of abemaciclib made it the third cyclin-dependent kinase (CDK) inhibitor approved for the treatment of hormone receptor (HR)-positive breast cancer, and the first to receive an approved indication as monotherapy in that setting. Abemaciclib is a small-molecule inhibitor of the CDK4 and CDK6 proteins, which are key gatekeepers of the cell cycle and frequently dysregulated in HR-positive breast cancer. On the basis of the randomized, placebo-controlled, multicenter phase 3 MONARCH-2 trial, it was approved in combination with fulvestrant for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer who had progressed during endocrine therapy.¹

A total of 669 women aged 18 years and older, with any menopausal status, an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) or nonmeasurable bone-only disease, were enrolled. Patients had progressed during neoadjuvant or adjuvant endocrine therapy, within 12 months of adjuvant endocrine therapy, or during frontline endocrine treatment for metastatic disease.

Those who had received more than 1 endocrine therapy or any prior chemotherapy for metastatic breast cancer or prior treatment with everolimus or CDK4/6 inhibitors, as well as those with the presence of visceral crisis or evidence or history of central nervous system (CNS) metastases, were excluded from the study.

Patients were randomized 2:1 to receive 150 mg abemaciclib or placebo, both in combination with 500 mg fulvestrant. The initial dose of abemaciclib was 200 mg, but this was amended to 150mg after enrollment of the first 178 patients to alleviate diarrhea-related toxicity concerns. Randomization was stratified according to metastatic site (visceral, bone only, or other) and endocrine therapy resistance (primary or secondary).

Tumors were measured by computed tomography (CT) and magnetic-resonance imaging (MRI) according to RECIST-1.1 within 28 days before random assignment, every 8 weeks for the first year, every 12 weeks thereafter, and then within 2 weeks of clinical progression. Bone scintigraphy was also performed at baseline and then every 6th cycle starting with cycle 7. Hematologic and blood chemistry laboratory tests were performed centrally on days 1 and 15 of the first cycle and day 1 of all remaining cycles.

The primary endpoint was progression-free survival (PFS); median PFS was 16.4 months in the abemaciclib arm, compared with 9.3 months in the placebo arm in the intent-to-treat population (hazard ratio [HR], 0.553;P < .0000001), translating to a 45% reduction in the risk of disease progression or death with the combination. Objective response rate in the 2 groups among patients with measurable disease was 48.1% and 21.3%, respectively, which included a complete response rate of 3.5% in the abemaciclib arm. The median duration of response was not yet reached in the study group, compared with 25.6 months for placebo. Overall survival data were not yet mature.

The agency also approved abemaciclib as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. That approval was based on data from the single-arm MONARCH-1 trial of 132 patients who received 200 mg abemaciclib twice daily on a continuous schedule.²

Patients had adequate organ function, measurable disease per RECIST-1.1, and an ECOG performance status of 0 or 1. Patients must have progressed on or after previous endocrine therapy and have received prior treatment with at least 2 chemotherapy regimens, at least 1 of them, but no more than 2, having been administered in the metastatic setting. Exclusion criteria included prior receipt of a CDK inhibitor, major surgery within 14 days of the start of the study, and CNS metastases.

Tumor assessments were performed by CT or MRI according to RECIST-1.1 within the 4 weeks prior to the first dose of study drug and then subsequently at every other cycle. Responses were confirmed at least 4 weeks after the initial observation. The overall response rate was 19.7%, made up completely of partial responses. Median duration of response was 8.6 months, median PFS was 6 months and median OS was 17.7 months.
 

Adverse events

The most common adverse events experienced with the combination of abemaciclib and fulvestrant were neutropenia (23.6%) and diarrhea (13.4%). The rate of grade 4 neutropenia was higher in the combination arm (2.9% vs 0.4%) and there were 3 deaths with the combination that were linked to treatment-related AEs. In the monotherapy trial, abemaciclib treatment most commonly caused diarrhea (90.2%), fatigue (65.2%), nausea (64.4%), decreased appetite (45.5%), and abdominal pain (38.6%). Grade 3 diarrhea and fatigue occurred in 19.7% and 12.9% of patients, respectively. Serious AEs occurred in 24.2% of patients and AEs led to treatment discontinuation in 7.6% of patients.

Warnings and precautions

Abemaciclib is marketed as Verzenio by Eli Lilly and Company. Warnings and precautions relating to diarrhea, neutropenia, hepatotoxicity, venous thromboembolism (VTE), and embryofetal toxicity are detailed in the prescribing information. In the event of diarrhea, patients should be treated with antidiarrheal therapy and should increase oral fluids and notify their health care provider. Treatment should be interrupted for grade 3 or 4 diarrhea and then resumed at a lower dose upon return to grade 1.

To guard against neutropenia, complete blood counts should be performed prior to starting therapy, every 2 weeks for the first 2 months, monthly for the subsequent 2 months, and then as clinically indicated. Treatment should be interrupted or delayed or the dose reduced for grade 3 or 4 neutropenia and patients should report episodes of fever.

Liver function tests should be performed before starting abemaciclib, every 2 weeks for the first 2 months, monthly for the next 2 months, and then as clinically indicated. For patients who develop persistent or recurrent grade 2, 3 or 4 hepatic transaminase elevation, dose interruption, reduction, discontinuation, or delay should be considered.

Patients should be monitored for signs and symptoms of VTE and pulmonary embolism, and treated appropriately. Pregnant women should be advised of the potential risk to a fetus, and those of reproductive potential should be counselled on the importance of using effective contraception during treatment and for at least 3 weeks after the last dose.³

The fall 2017 approval by the US Food and Drug Administration (FDA) of abemaciclib made it the third cyclin-dependent kinase (CDK) inhibitor approved for the treatment of hormone receptor (HR)-positive breast cancer, and the first to receive an approved indication as monotherapy in that setting. Abemaciclib is a small-molecule inhibitor of the CDK4 and CDK6 proteins, which are key gatekeepers of the cell cycle and frequently dysregulated in HR-positive breast cancer. On the basis of the randomized, placebo-controlled, multicenter phase 3 MONARCH-2 trial, it was approved in combination with fulvestrant for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer who had progressed during endocrine therapy.¹

A total of 669 women aged 18 years and older, with any menopausal status, an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) or nonmeasurable bone-only disease, were enrolled. Patients had progressed during neoadjuvant or adjuvant endocrine therapy, within 12 months of adjuvant endocrine therapy, or during frontline endocrine treatment for metastatic disease.

Those who had received more than 1 endocrine therapy or any prior chemotherapy for metastatic breast cancer or prior treatment with everolimus or CDK4/6 inhibitors, as well as those with the presence of visceral crisis or evidence or history of central nervous system (CNS) metastases, were excluded from the study.

Patients were randomized 2:1 to receive 150 mg abemaciclib or placebo, both in combination with 500 mg fulvestrant. The initial dose of abemaciclib was 200 mg, but this was amended to 150mg after enrollment of the first 178 patients to alleviate diarrhea-related toxicity concerns. Randomization was stratified according to metastatic site (visceral, bone only, or other) and endocrine therapy resistance (primary or secondary).

Tumors were measured by computed tomography (CT) and magnetic-resonance imaging (MRI) according to RECIST-1.1 within 28 days before random assignment, every 8 weeks for the first year, every 12 weeks thereafter, and then within 2 weeks of clinical progression. Bone scintigraphy was also performed at baseline and then every 6th cycle starting with cycle 7. Hematologic and blood chemistry laboratory tests were performed centrally on days 1 and 15 of the first cycle and day 1 of all remaining cycles.

The primary endpoint was progression-free survival (PFS); median PFS was 16.4 months in the abemaciclib arm, compared with 9.3 months in the placebo arm in the intent-to-treat population (hazard ratio [HR], 0.553;P < .0000001), translating to a 45% reduction in the risk of disease progression or death with the combination. Objective response rate in the 2 groups among patients with measurable disease was 48.1% and 21.3%, respectively, which included a complete response rate of 3.5% in the abemaciclib arm. The median duration of response was not yet reached in the study group, compared with 25.6 months for placebo. Overall survival data were not yet mature.

The agency also approved abemaciclib as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. That approval was based on data from the single-arm MONARCH-1 trial of 132 patients who received 200 mg abemaciclib twice daily on a continuous schedule.²

Patients had adequate organ function, measurable disease per RECIST-1.1, and an ECOG performance status of 0 or 1. Patients must have progressed on or after previous endocrine therapy and have received prior treatment with at least 2 chemotherapy regimens, at least 1 of them, but no more than 2, having been administered in the metastatic setting. Exclusion criteria included prior receipt of a CDK inhibitor, major surgery within 14 days of the start of the study, and CNS metastases.

Tumor assessments were performed by CT or MRI according to RECIST-1.1 within the 4 weeks prior to the first dose of study drug and then subsequently at every other cycle. Responses were confirmed at least 4 weeks after the initial observation. The overall response rate was 19.7%, made up completely of partial responses. Median duration of response was 8.6 months, median PFS was 6 months and median OS was 17.7 months.
 

Adverse events

The most common adverse events experienced with the combination of abemaciclib and fulvestrant were neutropenia (23.6%) and diarrhea (13.4%). The rate of grade 4 neutropenia was higher in the combination arm (2.9% vs 0.4%) and there were 3 deaths with the combination that were linked to treatment-related AEs. In the monotherapy trial, abemaciclib treatment most commonly caused diarrhea (90.2%), fatigue (65.2%), nausea (64.4%), decreased appetite (45.5%), and abdominal pain (38.6%). Grade 3 diarrhea and fatigue occurred in 19.7% and 12.9% of patients, respectively. Serious AEs occurred in 24.2% of patients and AEs led to treatment discontinuation in 7.6% of patients.

Warnings and precautions

Abemaciclib is marketed as Verzenio by Eli Lilly and Company. Warnings and precautions relating to diarrhea, neutropenia, hepatotoxicity, venous thromboembolism (VTE), and embryofetal toxicity are detailed in the prescribing information. In the event of diarrhea, patients should be treated with antidiarrheal therapy and should increase oral fluids and notify their health care provider. Treatment should be interrupted for grade 3 or 4 diarrhea and then resumed at a lower dose upon return to grade 1.

To guard against neutropenia, complete blood counts should be performed prior to starting therapy, every 2 weeks for the first 2 months, monthly for the subsequent 2 months, and then as clinically indicated. Treatment should be interrupted or delayed or the dose reduced for grade 3 or 4 neutropenia and patients should report episodes of fever.

Liver function tests should be performed before starting abemaciclib, every 2 weeks for the first 2 months, monthly for the next 2 months, and then as clinically indicated. For patients who develop persistent or recurrent grade 2, 3 or 4 hepatic transaminase elevation, dose interruption, reduction, discontinuation, or delay should be considered.

Patients should be monitored for signs and symptoms of VTE and pulmonary embolism, and treated appropriately. Pregnant women should be advised of the potential risk to a fetus, and those of reproductive potential should be counselled on the importance of using effective contraception during treatment and for at least 3 weeks after the last dose.³

ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.

Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.

“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.

Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.

The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.

At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.

There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.

It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.

“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.

Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
 

[email protected]

SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.

ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.

Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.

“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.

Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.

The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.

At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.

There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.

It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.

“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.

Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
 

[email protected]

SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.

ORLANDO – Physical exercise during adjuvant chemotherapy may lead to improved physical activity and decreased fatigue years after the treatment is completed, results of a recent analysis suggest.

Four years after participating in an exercise program that took place during cancer treatment, patients reported more moderate-to-vigorous activity and less fatigue, compared with patients who did not participate in the program, according to long-term follow-up results presented at the Cancer Survivorship Symposium.

“We think that offering exercise during cancer treatment, including chemotherapy, is recommended and has beneficial short- and long-term effects on health,” said Anne M. May, PhD, of University Medical Center, Utrecht, the Netherlands.

Speaking in a press conference at the symposium, Dr. May described results of the analysis, which included 128 patients who had previously participated in PACT, a 237-patient randomized controlled trial evaluating a supervised exercise program versus usual care in patients undergoing adjuvant treatment for breast or colon cancer.

The 18-week exercise program included moderate- to high-intensity aerobic and strength training under physical therapist supervision for 60 minutes twice weekly, plus home-based physical activity for 30 minutes three times weekly.

At 4 years’ follow-up, patients in the exercise group reported on average 90 minutes of moderate-to-vigorous exercise per week, compared to an average of 70 minutes per week in the usual care group (P less than .05), Dr. May reported at the symposium, which was sponsored by the American Academy of Family Physicians, the American College of Physicians, and the American Society of Clinical Oncology.

There was also a trend toward decreased fatigue reported in the exercise vs. usual care group, though the finding did not reach statistical significance, she said.

It is “encouraging” to see that this exercise program had a long-term impact on patients’ physical activity levels, said ASCO expert Timothy Gilligan, MD, MSc.

“I think the public sometimes gets jaded because the nutritional recommendations seem to change every year, but if you look at the research on exercise in health … it’s interesting how consistent the data is that exercise really is good for us – if we can only get people to do it,” said Dr. Gilligan, who moderated the press conference.

Dr. May said she had no disclosures to report for the study, which was supported by grants from the Dutch Cancer Society, the Dutch Pink Ribbon Foundation, and the Netherlands Organization for Health Research.
 

[email protected]

SOURCE: May AM et al. Cancer Survivorship Symposium, Abstract 99.

Adding metronomic oral cyclophosphamide to trastuzumab and pertuzumab in frail elderly women with human epidermal growth factor receptor 2–positive metastatic breast cancer improved median progression-free survival by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.

After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.

The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.

Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.

“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”

Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.

This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.

[email protected]

SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.

Adding metronomic oral cyclophosphamide to trastuzumab and pertuzumab in frail elderly women with human epidermal growth factor receptor 2–positive metastatic breast cancer improved median progression-free survival by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.

After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.

The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.

Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.

“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”

Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.

This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.

[email protected]

SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.

Adding metronomic oral cyclophosphamide to trastuzumab and pertuzumab in frail elderly women with human epidermal growth factor receptor 2–positive metastatic breast cancer improved median progression-free survival by 7 months – with acceptable toxicity – vs. dual HER2 blockade alone in a randomized, open-label, phase 2 trial.

After a median follow-up of 20.7 months, the median progression-free survival (PFS) among 41 women who received trastuzumab and pertuzumab plus metronomic oral cyclophosphamide was 12.7 months, compared with 5.6 months among 39 women who received only trastuzumab and pertuzumab. Estimated PFS at 6 months was 73.4% and 46.2% in the groups, respectively (hazard ratio, 0.65), Hans Wildiers, MD, PhD, of University Hospitals Leuven, Belgium, and his colleagues reported in Lancet Oncology.

The most frequent grade 3-4 adverse events occurring in each group, respectively, were hypertension (12% and 15%), diarrhea (12% and 10%), dyspnea (10% and 5%), fatigue (5% and 8%), and pain (5% in each group). Thromboembolic events occurred in four patients (10%) receiving cyclophosphamide, while none occurred in the dual HER2 blockade-only group. Severe cardiac toxicities were occasionally observed in both groups.

Study subjects were women aged at least 70 years, or at least 60 years with confirmed functional restrictions. All had confirmed HER2-positive metastatic breast cancer and no prior chemotherapy for metastatic disease. They received either intravenous trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks, and intravenous pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks (median of 6 cycles), or those same doses of trastuzumab and pertuzumab plus metronomic oral cyclophosphamide at a dose of 50 mg daily (median of 13 cycles). Subsequent treatment with trastuzumab emtansine in 29 patients who progressed during the study was active and well tolerated; the overall PFS at 6 months in this group of patients was 49.5% and median PFS was 5 months after starting trastuzumab emtansine.

“The results of this study indicate that the benefit of avoiding the side effects of chemotherapy with the use of dual anti–HER2 blockade only does not compensate for an important loss of activity in the metastatic setting,” the investigators wrote, concluding that “trastuzumab and pertuzumab plus metronomic oral cyclophosphamide, potentially followed by trastuzumab emtansine after progression, might delay the need for, or supersede, the use of taxane-based chemotherapy in this population.”

Further evaluation of this combination in a randomized phase 3 study is warranted, as the phase 2 findings do not provide “robust justification for a change in practice.” They do, however, provide a scientific framework for supporting more specific trials in older patients, who compromise nearly a third of breast cancer patients worldwide, and up to 50% in high-income countries, they said.

This study was funded by F Hoffmann-La Roche. Dr. Wildiers has received research grants from Roche, and personal fees to his institute from Roche, Amgen, Novartis, Pfizer, Puma, and Celldex. Other authors also reported receiving research or other support from Roche Products, Eisai, Novartis Pharmaceuticals UK, Astellas/Medivation, Astra Zeneca, Celgene, Daiichi-Sankyo, GE Oncology, Genentech, GlaxoSmithKline, Macrogenics, Merck Sharp & Dohme, Merus BV, Mylan, Novartis, Pfizer, Pierre Fabre, Sanofi, and Teva.

[email protected]

SOURCE: Wildiers H et al. Lancet Oncol. 2018 Feb 9. doi: 10.1016/S1470-2045(18)30083-4.

The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.

This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.

The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.

Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.

The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.

“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.

The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.

Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.

Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
 

[email protected]

SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.

The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.

This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.

The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.

Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.

The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.

“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.

The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.

Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.

Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
 

[email protected]

SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.

The PAM50-based risk of recurrence (ROR) score enabled selection of a subset of patients with estrogen receptor (ER)–positive early-stage breast cancer with node-positive or node-negative disease with an estimated 10-year distant recurrence (DR) absolute risk of less than 5%, investigators reported.

This subset of patients with one to three positive lymph nodes presented a sufficiently low risk of disease recurrence and could safely avoid chemotherapy, reported Anne-Vibeke Laenkholm, MD, and her associates. The report was published in the Journal of Clinical Oncology.

The PAM50-based ROR score (Prosigna Score; Nanostring Technologies, Seattle) is a comparative gene expression profile of the tumor, relative to each of the four PAM50 molecular profiles (luminal A, luminal B, basal, and HER2 enriched) to determine the degree of similarity. The Prosigna assay currently has Food and Drug Administration clearance for prognostic use.

Postmenopausal women diagnosed with ER-positive/HER2-negative early-stage breast cancer in Denmark between 2000 and 2003, and who received adjuvant treatment with tamoxifen or an aromatase inhibitor without chemotherapy were eligible for this cohort study.

The primary endpoint was time to DR, defined as the interval from breast cancer surgery until DR or death as a result of breast cancer. Secondary endpoints included overall survival and time to any recurrence. “The median age of patients was 63 years (range, 50-89 years); 45.5% were node negative, and 54.5% had one to three positive nodes. Tumor characteristics including nodal status, tumor size, malignancy grade, and lymphovascular invasion were all associated with DR, whereas treatment adherence was not,” wrote Dr. Laenkholm of the department of surgical pathology, Zealand University Hospital, Denmark, and her colleagues.

“With a median follow-up of approximately 9 years, 26% of the patients with node-positive disease were categorized as having a low ROR score corresponding to a DR of 3.5% at 10 years compared with those with an intermediate ROR score with a DR of 11.5% and those with a high ROR score corresponding to a DR risk of 22%. In the node-negative group, those with a low ROR score had a 10-year DR risk of 5% and those with an intermediate ROR score had a 7.3% 10-year DR risk, compared with a DR of 17.8% in those with a high ROR score,” Dr. Laenkholm and her associates reported.

The data are entirely prognostic and do not address whether chemotherapy might offer some benefit in a node-positive population (i.e., one to three nodes), or whether adjuvant chemotherapy–associated adverse effects may offset the added benefit, if any, the investigators said.

Nonetheless, genomic assay–based scoring tools are an important aid in clinical decision making readily available to the physician at the patient’s bedside, they said.

Nanostring Technologies funded the study. Laboratory work flow was executed at the department of surgical pathology, Zealand University Hospital. Several authors reported ties with Roche and other pharmaceutical companies.
 

[email protected]

SOURCE: Laenkholm et al. J Clin Oncol. 2018 Jan 25. doi: 10.1200/JCO.2017.74.6586.

Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.

The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.

Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.

Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.

Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.

A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.

Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.

Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.

To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.

In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.

Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.

Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.

“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.

Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.

[email protected]

SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.

Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.

The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.

Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.

Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.

Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.

A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.

Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.

Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.

To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.

In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.

Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.

Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.

“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.

Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.

[email protected]

SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.

Breast cancer outcomes rely on “coexisting cardiovascular health” at every step in the patient journey, the American Heart Association has said in its first-ever scientific statement on the matter.

The statement, published in Circulation provides a comprehensive overview of cardiovascular disease and breast cancer prevalence and shared risk factors, as well as current recommendations on avoiding the cardiotoxic effects of some cancer treatments and strategies to prevent or treat CVD in breast cancer patients.

Breast cancer and CVD share a number of common and sometimes modifiable risk factors, including dietary patterns, physical activity, and being overweight or obese, and tobacco use. There is “growing awareness” that modifying those risk factors may help prevent some cases of breast cancer.

Even in patients who have a breast cancer diagnosis, “from a cardiology standpoint, lifestyle is going to be key,” said Dr. Mehta. She said breast cancer patients can be encouraged to follow AHA recommendations to aim for 150 minutes of moderate aerobic exercise weekly and to follow an “overall healthy dietary pattern” that limits saturated and trans fats, sodium, red meat, sweets, and sugar-sweetened beverages.

Although left ventricular systolic dysfunction is the most common cardiovascular side effect associated with chemotherapy, other manifestations of early or delayed cardiotoxicity can include heart failure, hypertension, thromboembolic disease, pulmonary hypertension, pericarditis, and myocardial ischemia, according to the AHA scientific statement.

A wide range of standard breast cancer treatments cause cardiovascular adverse effects, including taxanes such as paclitaxel, anthracyclines such as doxorubicin, and alkylating agents such as cisplatin and cyclophosphamide, as outlined in the statement.

Targeted HER-2–directed therapies, including trastuzumab and pertuzumab, are associated with left ventricular dysfunction and heart failure, while emerging therapies, such as the cyclin-dependent kinase 4/6 inhibitors palbociclib and ribociclib, are associated with QTc prolongation, the statement also notes.

Current strategies for monitoring for cardiovascular toxicity, which typically involve myocardial strain imaging, assessing cardiac biomarkers, or a combination of imaging and biomarkers, are outlined in the report.

To mitigate the impact of cancer treatments on cardiovascular health, several oncologic strategies are useful, according to Dr. Mehta and colleagues.

In multiple clinical trials of breast cancer patients receiving doxorubicin or epirubicin, the iron-binding agent dexrazoxane reduced the combined endpoint of decreased left ventricular ejection fraction or development of heart failure, the authors said.

Likewise, clinical trial evidence has suggested cardiotoxicity associated with doxorubicin can be mitigated through administration via infusion as opposed to bolus and with longer versus shorter infusion durations, they continued.

Extreme cases or difficult-to-manage patients can be referred to a center that has an active program in cardio-oncology, a newer and rapidly expanding field, according to Dr. Mehta.

“That’s where there’s tight collaboration in terms of understanding the current treatments, and that’s also where research on how to best take care of these patients will be conducted,” she said.

Dr. Mehta reported no disclosures. Coauthors reported disclosures related to Amgen, Boehringer Ingelheim, Genentech, AstraZeneca, Lilly, Roche, Novartis, and others.

[email protected]

SOURCE: Mehta LS et al. Circulation. 2017 Jan 22. doi: 10.1161/CIR.0000000000000556.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Young women with primary Hodgkin lymphoma had an increased relative risk of estrogen receptor–positive breast cancer if they received radiotherapy and, irrespective of the type of treatment they got, an elevated risk of ER-negative breast cancer, based on results of a study based on patient records from 12 U.S. National Cancer Institute Surveillance, Epidemiology, and End Results registries.

Of 7,355 women diagnosed with primary Hodgkin lymphoma during 1973-2009 and aged 10-39 years, 377 patients subsequently were diagnosed with breast cancer at a mean age of 45 years; 57% of the cancers were ER positive, 34% were ER negative, and 9% had unknown/borderline ER status, Diana R. Withrow, PhD, and her colleagues from the radiation epidemiology branch, division of cancer epidemiology and genetics, National Cancer Institute reported in JAMA Oncology.

Survivors of Hodgkin lymphoma had a greater relative risk of ER-negative (standardized incidence ratio, 5.8; 95% confidence interval, 4.8-6.9) than ER-positive breast cancer (SIR, 3.1; 95% CI, 2.7-3.5; P less than .001 for the difference), the researchers wrote.

For ER-positive disease, the increased SIR was observed only among women who had received radiotherapy for their Hodgkin lymphoma (SIR, 3.9; 95% CI, 3.4-4.5). In this group, the SIR for ER-positive disease was lower in the chemotherapy than in the no/unknown chemotherapy group (P = .04), said the researchers.

The authors acknowledged that lack of information on patient risk factors such as family history, reproductive factors, and hormone therapy, as well as detailed treatment information such as radiotherapy dose, fields, specific chemotherapeutic agents, and subsequent therapy is a limitation of the current study. Further research, including comprehensive treatment records, will lead to a better understanding of the association between treatment and breast cancer subtype in these patients, the researchers concluded.

None of the study authors reported any conflicts of interest.

SOURCE: Withrow D et al. doi: 10.1001/jamaoncol.2017.4887.

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.

Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

[email protected]

SOURCE: Lemons J et al., ASCO-SITC abstract #20.

SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.

Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

[email protected]

SOURCE: Lemons J et al., ASCO-SITC abstract #20.

SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.

Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

[email protected]

SOURCE: Lemons J et al., ASCO-SITC abstract #20.

More women received recommended mammograms after cost sharing for the service was eliminated under the Affordable Care Act, a study shows.

In health plans that eliminated cost sharing, such as copays, deductibles, or other out-of-pocket costs, the rate of biennial screening mammography increased from 60% in the 2-year period before the cost-sharing elimination to 65% in the 2-year period following the new regulation, according to an analysis in the New England Journal of Medicine.

John Foxx/Thinkstock

The findings extend that of past studies that show older women who need mammograms are sensitive to out-of-pocket costs and the presence of supplemental coverage, the authors conclude. If the cost-sharing provisions of the ACA are rescinded, the results also “raise concern that fewer older women will receive recommended breast-cancer screening.”

However, the authors also note that since mammogram rates in the health plans that eliminated cost sharing remained below those in plans with full coverage and less than three-quarters of women in control plans received biennial breast cancer screenings, that “the removal of out-of-pocket payments alone may not raise screening rates to desired levels.”

[email protected]

SOURCE: Trivedi A et al. N Engl J Med. 2018 Jan 18;378:262-9.
 

More women received recommended mammograms after cost sharing for the service was eliminated under the Affordable Care Act, a study shows.

In health plans that eliminated cost sharing, such as copays, deductibles, or other out-of-pocket costs, the rate of biennial screening mammography increased from 60% in the 2-year period before the cost-sharing elimination to 65% in the 2-year period following the new regulation, according to an analysis in the New England Journal of Medicine.

John Foxx/Thinkstock

The findings extend that of past studies that show older women who need mammograms are sensitive to out-of-pocket costs and the presence of supplemental coverage, the authors conclude. If the cost-sharing provisions of the ACA are rescinded, the results also “raise concern that fewer older women will receive recommended breast-cancer screening.”

However, the authors also note that since mammogram rates in the health plans that eliminated cost sharing remained below those in plans with full coverage and less than three-quarters of women in control plans received biennial breast cancer screenings, that “the removal of out-of-pocket payments alone may not raise screening rates to desired levels.”

[email protected]

SOURCE: Trivedi A et al. N Engl J Med. 2018 Jan 18;378:262-9.
 

More women received recommended mammograms after cost sharing for the service was eliminated under the Affordable Care Act, a study shows.

In health plans that eliminated cost sharing, such as copays, deductibles, or other out-of-pocket costs, the rate of biennial screening mammography increased from 60% in the 2-year period before the cost-sharing elimination to 65% in the 2-year period following the new regulation, according to an analysis in the New England Journal of Medicine.

John Foxx/Thinkstock

The findings extend that of past studies that show older women who need mammograms are sensitive to out-of-pocket costs and the presence of supplemental coverage, the authors conclude. If the cost-sharing provisions of the ACA are rescinded, the results also “raise concern that fewer older women will receive recommended breast-cancer screening.”

However, the authors also note that since mammogram rates in the health plans that eliminated cost sharing remained below those in plans with full coverage and less than three-quarters of women in control plans received biennial breast cancer screenings, that “the removal of out-of-pocket payments alone may not raise screening rates to desired levels.”

[email protected]

SOURCE: Trivedi A et al. N Engl J Med. 2018 Jan 18;378:262-9.
 

Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.

It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.

SilverV/Thinkstock

CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.

The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.

SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247.

Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.

It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.

SilverV/Thinkstock

CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.

The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.

SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247.

Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.

It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.

SilverV/Thinkstock

CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.

The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.

SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247.