SABCS 2017

SAN ANTONIO – The phase 3 SOLD trial failed to show a 9-week course of trastuzumab as noninferior to the standard 12-month course when combined with chemotherapy for women with early-stage HER2-positive breast cancer.

Disease-free survival (DFS) with a 9-week course of adjuvant trastuzumab (Herceptin)did not pass muster as noninferior to the standard 12 months, reported Dr. Heikki Joensuu, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki.

“The non-inferiority of 9 week administration of trastuzumab plus docetaxel could not be demonstrated in terms of disease free survival, as compared to chemotherapy and one year duration of adjuvant trastuzumab.”

Based on these findings, he noted that chemotherapy plus one year of anti-HER2 therapy should remain the standard of care.

However, the dose of docetaxel administered along with trastuzumab could influence survival outcomes. Patients who received a higher dose of docetaxel in the 9 week cohort had similar DFS as those who received 12 months of trastuzumab.

Dr. Joensuu explained that the regimen of giving trastuzumab for one year is an arbitrary one and is not based on research data. In the four large randomized trials that established the current standard treatment for this population of breast cancer patients, trastuzumab was administered for one year and that eventually became the standard of care, he said at the San Antonio Breast Cancer Symposium.

But in two randomized trials that had relatively limited statistical power, a statistically significant difference in DFS or overall survival was not observed between patients who received only nine weeks of trastuzumab compared with those who received the one year regimen.

In addition, the one year treatment course is costly and has been associated with cardiac-related adverse events, although it is relatively uncommon (less than 3% of patients).

The phase 3 SOLD (Synergism or Long Duration) clinical trial was conducted by Dr. Joensuu and his colleagues to compare DFS between women treated with 9 weeks of concomitant trastuzumab plus docetaxel followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to that of women treated with the same regimen followed by single-agent trastuzumab for a one year duration.

The cohort included 2,176 patients with early-stage HER2-positive breast cancer who were randomized to either the 9-week or the 12-month trastuzumab arm. In addition, cardiac function among women enrolled in the trial had to be normal, Dr. Joensuu said, as determined by left ventricular ejection fraction of 50% or greater.

Patients in both groups received three cycles of docetaxel (80 mg/m² or 100 mg/m²) and trastuzumab three times a week, followed by three cycles of FEC. The dose of docetaxel was determined by the individual center. Patients in the 12-month arm continued to receive trastuzumab every 3 weeks for 14 cycles and in both groups, those with estrogen receptor–positive cancer received appropriate endocrine treatment per guidelines.

“SOLD was initially designed as a superiority trial,” he said, “But, we redesigned the study and the size during the study because we noticed that the assumptions we made for 5-year disease-free survival were too low.”

“We also realized that the shorter arm cannot be better than the longer arm because less drug is given,” said Dr. Joensuu. “So we changed it from a superiority trial to a noninferiority design, where the shorter arm would be at least equal to the longer arm.”

When looking at results, the DFS favored the longer arm: 90.5% in the 12-month arm vs. 88% in the 9-week arm (hazard ratio, 1.39; 90% confidence interval, 1.12-1.72). However, there were no substantial differences in secondary endpoints. Five-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 12-month arm (HR, 1.24; 90% CI, 0.93-1.65), and similarly, 5-year overall survival was 94.7% vs. 95.9% (HR, 1.39; 90% CI, 0.98-1.89).

There was an interaction between the dose of docetaxel given concomitantly with trastuzumab. For patients who received 100 mg/m² docetaxel, DFS was similar in both groups: 92.2% (long arm) vs. 87.8% (short arm) (HR 0.71, 90% CI 0,44-1.14). But among those who received 80 mg/m² docetaxel, DFS was superior in the group who received 12 months of trastuzumab, compared with the 9-week group (91.3% vs. 86.8%; HR, 1.66; 90% CI, 1.30-2.11).

Less cardiac toxicity was observed in the 9-week group, for any protocol-defined cardiac adverse event (n = 22 [2%] vs. n = 42 [3.9%]; P = .012) and for heart failure (n = 21 [1.9%] vs. n = 36 [3.3%]; P = .046).

“Docetaxel dosing with trastuzumab requires further study,” Dr. Joensuu said.

SOURCE: Joensuu H et al., Abstract GS3-04

SAN ANTONIO – The phase 3 SOLD trial failed to show a 9-week course of trastuzumab as noninferior to the standard 12-month course when combined with chemotherapy for women with early-stage HER2-positive breast cancer.

Disease-free survival (DFS) with a 9-week course of adjuvant trastuzumab (Herceptin)did not pass muster as noninferior to the standard 12 months, reported Dr. Heikki Joensuu, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki.

“The non-inferiority of 9 week administration of trastuzumab plus docetaxel could not be demonstrated in terms of disease free survival, as compared to chemotherapy and one year duration of adjuvant trastuzumab.”

Based on these findings, he noted that chemotherapy plus one year of anti-HER2 therapy should remain the standard of care.

However, the dose of docetaxel administered along with trastuzumab could influence survival outcomes. Patients who received a higher dose of docetaxel in the 9 week cohort had similar DFS as those who received 12 months of trastuzumab.

Dr. Joensuu explained that the regimen of giving trastuzumab for one year is an arbitrary one and is not based on research data. In the four large randomized trials that established the current standard treatment for this population of breast cancer patients, trastuzumab was administered for one year and that eventually became the standard of care, he said at the San Antonio Breast Cancer Symposium.

But in two randomized trials that had relatively limited statistical power, a statistically significant difference in DFS or overall survival was not observed between patients who received only nine weeks of trastuzumab compared with those who received the one year regimen.

In addition, the one year treatment course is costly and has been associated with cardiac-related adverse events, although it is relatively uncommon (less than 3% of patients).

The phase 3 SOLD (Synergism or Long Duration) clinical trial was conducted by Dr. Joensuu and his colleagues to compare DFS between women treated with 9 weeks of concomitant trastuzumab plus docetaxel followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to that of women treated with the same regimen followed by single-agent trastuzumab for a one year duration.

The cohort included 2,176 patients with early-stage HER2-positive breast cancer who were randomized to either the 9-week or the 12-month trastuzumab arm. In addition, cardiac function among women enrolled in the trial had to be normal, Dr. Joensuu said, as determined by left ventricular ejection fraction of 50% or greater.

Patients in both groups received three cycles of docetaxel (80 mg/m² or 100 mg/m²) and trastuzumab three times a week, followed by three cycles of FEC. The dose of docetaxel was determined by the individual center. Patients in the 12-month arm continued to receive trastuzumab every 3 weeks for 14 cycles and in both groups, those with estrogen receptor–positive cancer received appropriate endocrine treatment per guidelines.

“SOLD was initially designed as a superiority trial,” he said, “But, we redesigned the study and the size during the study because we noticed that the assumptions we made for 5-year disease-free survival were too low.”

“We also realized that the shorter arm cannot be better than the longer arm because less drug is given,” said Dr. Joensuu. “So we changed it from a superiority trial to a noninferiority design, where the shorter arm would be at least equal to the longer arm.”

When looking at results, the DFS favored the longer arm: 90.5% in the 12-month arm vs. 88% in the 9-week arm (hazard ratio, 1.39; 90% confidence interval, 1.12-1.72). However, there were no substantial differences in secondary endpoints. Five-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 12-month arm (HR, 1.24; 90% CI, 0.93-1.65), and similarly, 5-year overall survival was 94.7% vs. 95.9% (HR, 1.39; 90% CI, 0.98-1.89).

There was an interaction between the dose of docetaxel given concomitantly with trastuzumab. For patients who received 100 mg/m² docetaxel, DFS was similar in both groups: 92.2% (long arm) vs. 87.8% (short arm) (HR 0.71, 90% CI 0,44-1.14). But among those who received 80 mg/m² docetaxel, DFS was superior in the group who received 12 months of trastuzumab, compared with the 9-week group (91.3% vs. 86.8%; HR, 1.66; 90% CI, 1.30-2.11).

Less cardiac toxicity was observed in the 9-week group, for any protocol-defined cardiac adverse event (n = 22 [2%] vs. n = 42 [3.9%]; P = .012) and for heart failure (n = 21 [1.9%] vs. n = 36 [3.3%]; P = .046).

“Docetaxel dosing with trastuzumab requires further study,” Dr. Joensuu said.

SOURCE: Joensuu H et al., Abstract GS3-04

SAN ANTONIO – The phase 3 SOLD trial failed to show a 9-week course of trastuzumab as noninferior to the standard 12-month course when combined with chemotherapy for women with early-stage HER2-positive breast cancer.

Disease-free survival (DFS) with a 9-week course of adjuvant trastuzumab (Herceptin)did not pass muster as noninferior to the standard 12 months, reported Dr. Heikki Joensuu, professor in the department of oncology at the Helsinki University Hospital and University of Helsinki.

“The non-inferiority of 9 week administration of trastuzumab plus docetaxel could not be demonstrated in terms of disease free survival, as compared to chemotherapy and one year duration of adjuvant trastuzumab.”

Based on these findings, he noted that chemotherapy plus one year of anti-HER2 therapy should remain the standard of care.

However, the dose of docetaxel administered along with trastuzumab could influence survival outcomes. Patients who received a higher dose of docetaxel in the 9 week cohort had similar DFS as those who received 12 months of trastuzumab.

Dr. Joensuu explained that the regimen of giving trastuzumab for one year is an arbitrary one and is not based on research data. In the four large randomized trials that established the current standard treatment for this population of breast cancer patients, trastuzumab was administered for one year and that eventually became the standard of care, he said at the San Antonio Breast Cancer Symposium.

But in two randomized trials that had relatively limited statistical power, a statistically significant difference in DFS or overall survival was not observed between patients who received only nine weeks of trastuzumab compared with those who received the one year regimen.

In addition, the one year treatment course is costly and has been associated with cardiac-related adverse events, although it is relatively uncommon (less than 3% of patients).

The phase 3 SOLD (Synergism or Long Duration) clinical trial was conducted by Dr. Joensuu and his colleagues to compare DFS between women treated with 9 weeks of concomitant trastuzumab plus docetaxel followed by 5-FU, epirubicin, and cyclophosphamide (FEC) to that of women treated with the same regimen followed by single-agent trastuzumab for a one year duration.

The cohort included 2,176 patients with early-stage HER2-positive breast cancer who were randomized to either the 9-week or the 12-month trastuzumab arm. In addition, cardiac function among women enrolled in the trial had to be normal, Dr. Joensuu said, as determined by left ventricular ejection fraction of 50% or greater.

Patients in both groups received three cycles of docetaxel (80 mg/m² or 100 mg/m²) and trastuzumab three times a week, followed by three cycles of FEC. The dose of docetaxel was determined by the individual center. Patients in the 12-month arm continued to receive trastuzumab every 3 weeks for 14 cycles and in both groups, those with estrogen receptor–positive cancer received appropriate endocrine treatment per guidelines.

“SOLD was initially designed as a superiority trial,” he said, “But, we redesigned the study and the size during the study because we noticed that the assumptions we made for 5-year disease-free survival were too low.”

“We also realized that the shorter arm cannot be better than the longer arm because less drug is given,” said Dr. Joensuu. “So we changed it from a superiority trial to a noninferiority design, where the shorter arm would be at least equal to the longer arm.”

When looking at results, the DFS favored the longer arm: 90.5% in the 12-month arm vs. 88% in the 9-week arm (hazard ratio, 1.39; 90% confidence interval, 1.12-1.72). However, there were no substantial differences in secondary endpoints. Five-year distant DFS was 93.2% in the 9-week arm vs. 94.2% in the 12-month arm (HR, 1.24; 90% CI, 0.93-1.65), and similarly, 5-year overall survival was 94.7% vs. 95.9% (HR, 1.39; 90% CI, 0.98-1.89).

There was an interaction between the dose of docetaxel given concomitantly with trastuzumab. For patients who received 100 mg/m² docetaxel, DFS was similar in both groups: 92.2% (long arm) vs. 87.8% (short arm) (HR 0.71, 90% CI 0,44-1.14). But among those who received 80 mg/m² docetaxel, DFS was superior in the group who received 12 months of trastuzumab, compared with the 9-week group (91.3% vs. 86.8%; HR, 1.66; 90% CI, 1.30-2.11).

Less cardiac toxicity was observed in the 9-week group, for any protocol-defined cardiac adverse event (n = 22 [2%] vs. n = 42 [3.9%]; P = .012) and for heart failure (n = 21 [1.9%] vs. n = 36 [3.3%]; P = .046).

“Docetaxel dosing with trastuzumab requires further study,” Dr. Joensuu said.

SOURCE: Joensuu H et al., Abstract GS3-04

SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.

In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.

SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01

SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.

In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.

SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01

SAN ANTONIO – Five years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer, Austrian investigators reported.

In fact, the only thing that the additional years of the aromatase inhibitor (AI) anastrozole seemed to add was increased risk for fracture, said Michael Gnant, MD, from the Medical University of Vienna, on behalf of colleagues in the ABCSG-16 trial.

SOURCE: Gnant et al. SABCS 2017 Abstract GS3-01

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.

Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.

The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.

op@frontlinemedcom.com

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.

Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.

The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.

op@frontlinemedcom.com

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life scores.

Previous clinical trials have shown the advantage of adding a CDK4/6 inhibitor to standard aromatase inhibitor therapy in postmenopausal women, but the randomized phase 3 MONALEESA-7 trial is the first phase 3 study of an agent in this class in premenopausal women with breast cancer, and is the first randomized trial in this population in nearly 2 decades, notes Debu Tripathy, MD, from the University of Texas MD Anderson Cancer Center in Houston.

The median PFS for women treated with ribociclib plus endocrine therapy with either an aromatase inhibitor or tamoxifen plus the lutenizing hormone-releasing hormone agonist goserelin was 23.8 months, compared with 13 months for women treated with the same combination except for a ribociclib placebo.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Tripathy discusses the therapeutic benefits and quality of life improvements associated with adding ribociclib to endocrine therapy and ovarian suppression in this population.

The MONALEESA 7 trial was supported by Novartis. Dr. Tripathy disclosed steering committee consulting fees and institutional funding from the company.

op@frontlinemedcom.com

SAN ANTONIO – Acupuncture significantly reduced joint pain that was associated with the use of aromatase inhibitors (AIs) in women with early breast cancer, according to new findings reported at the San Antonio Breast Cancer Symposium.

The randomized, phase 3 SWOG S1200 clinical trial found that, compared with sham acupuncture and a control group receiving no therapy, women receiving acupuncture reported significantly lower scores on the Brief Pain Inventory–Short Form (BPI).

“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter trial,” said lead author Dawn L. Hershman, MD, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. “Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence and subsequent breast cancer outcomes.”

AIs can reduce both early breast cancer recurrence and mortality. Dr. Hershman noted that these agents are effective in the adjuvant setting and for prevention “but we know that it doesn’t work if you don’t take it. Noncompliance is a major problem among women taking hormonal therapy.”

Noncompliance is multifactorial and one of the main reasons women discontinue their therapy early is because of arthralgias or joint discomfort. “We were interested in a nonpharmacologic intervention, to assess whether or not we could control these symptoms.”

Dr. Hershman pointed out acupuncture provides a safe and effective alternative for patients reluctant to take a prescription medication that can result in other side effects. “Identification of nonopioid options for pain control is a public health priority,” she said.

Acupuncture is a popular nonpharmacologic modality and widely used for a number of indications. Several single-institution studies have suggested that it may be useful for controlling AI-associated arthralgias, while other studies have not demonstrated a benefit.

In this trial, the authors evaluated the efficacy of acupuncture, compared with sham acupuncture or waitlist control, in the treatment of AI associated arthralgia in a large population of patients. The study was conducted at 11 centers.

The cohort comprised 226 postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer who were receiving treatment with AIs. The primary endpoint was the decline in joint pain as measured by BPI-SF at 6 weeks, and to assess the duration of the effect, the women were followed for an additional 12 weeks.

Within this group, 110 were randomized to true acupuncture; 59 to sham acupuncture, and 57 to waitlist control (no treatment). Patients receiving true or sham acupuncture had sessions three times a week for 6 weeks followed by one session per week for 6 more weeks. Pain status was reported at baseline, during treatment, and then afterwards, using a variety of measurement tools including the BPI-SF, which is a self-administered 14-item questionnaire that evaluates pain severity on a 0-10 scale, and the impact of pain on activities of daily living.

At 6 weeks, the true acupuncture treatment arm reported significantly lower BPI worst pain scores than those in the sham acupuncture and the waitlist control arms. The mean BPI worst pain for the true acupuncture arm was 0.92 points lower than the sham acupuncture arm (P = .01) and 0.96 points lower than the waitlist control arm (P = .01). The proportion of patients experiencing a large reduction in BPI worst pain (greater than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively. The differences continued to remain statistically significant at 24 weeks, even though the treatment only continued for 12 weeks.

Associated adverse effects were minimal with true and sham acupuncture and limited to grade 1 bruising.

The cost of the 12-week intervention was about $1,250 or $65-$75 a session. “We feel that there is now sufficient evidence to support insurance coverage of acupuncture of AI arthralgia.”

In a discussion of the paper, Dr. Anne Partridge, from the Dana Farber Cancer Center, noted that it is imperative to seek new ways to improve outcomes in breast cancer, and AIs are contributing to that. However, she echoed the concern that nonadherence to treatment is a “tremendous problem” and hampers the clinical effectiveness of AI therapy.

The rate of discontinuation during the first year of therapy is 20% within the first year and up to 40% of patients do not take them daily. Both early discontinuation and nonadherence contribute to mortality.

Based on these results from the largest randomized controlled trial looking at acupuncture in this setting, should physicians be recommending acupuncture to patients prescribed AI therapy?

“The short answer is, why not?” said Dr. Partridge, “And that we should be recommending it for some of our patients.”

However, there are a number of issues that need to be addressed, she added. The duration of treatment is not known, and the need for follow-up treatment or the frequency of it is not known. The generalizability of it is also unclear when looking at a larger population, and acupuncture is highly operator dependent.

“There are cost and access issues, and insurance right now offers very limited coverage,” she said.

Importantly, Dr. Partridge emphasized, “We know that it will help symptoms, but will it improve adherence to AI?”

It may improve adherence for some patients, but “side effects are only one factor,” she said. “Adherence behavior is complicated. We need to figure out how to optimize these therapies in our patients.”

This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.

SOURCE: Hershman et al. Abstract GS4-04

SAN ANTONIO – Acupuncture significantly reduced joint pain that was associated with the use of aromatase inhibitors (AIs) in women with early breast cancer, according to new findings reported at the San Antonio Breast Cancer Symposium.

The randomized, phase 3 SWOG S1200 clinical trial found that, compared with sham acupuncture and a control group receiving no therapy, women receiving acupuncture reported significantly lower scores on the Brief Pain Inventory–Short Form (BPI).

“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter trial,” said lead author Dawn L. Hershman, MD, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. “Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence and subsequent breast cancer outcomes.”

AIs can reduce both early breast cancer recurrence and mortality. Dr. Hershman noted that these agents are effective in the adjuvant setting and for prevention “but we know that it doesn’t work if you don’t take it. Noncompliance is a major problem among women taking hormonal therapy.”

Noncompliance is multifactorial and one of the main reasons women discontinue their therapy early is because of arthralgias or joint discomfort. “We were interested in a nonpharmacologic intervention, to assess whether or not we could control these symptoms.”

Dr. Hershman pointed out acupuncture provides a safe and effective alternative for patients reluctant to take a prescription medication that can result in other side effects. “Identification of nonopioid options for pain control is a public health priority,” she said.

Acupuncture is a popular nonpharmacologic modality and widely used for a number of indications. Several single-institution studies have suggested that it may be useful for controlling AI-associated arthralgias, while other studies have not demonstrated a benefit.

In this trial, the authors evaluated the efficacy of acupuncture, compared with sham acupuncture or waitlist control, in the treatment of AI associated arthralgia in a large population of patients. The study was conducted at 11 centers.

The cohort comprised 226 postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer who were receiving treatment with AIs. The primary endpoint was the decline in joint pain as measured by BPI-SF at 6 weeks, and to assess the duration of the effect, the women were followed for an additional 12 weeks.

Within this group, 110 were randomized to true acupuncture; 59 to sham acupuncture, and 57 to waitlist control (no treatment). Patients receiving true or sham acupuncture had sessions three times a week for 6 weeks followed by one session per week for 6 more weeks. Pain status was reported at baseline, during treatment, and then afterwards, using a variety of measurement tools including the BPI-SF, which is a self-administered 14-item questionnaire that evaluates pain severity on a 0-10 scale, and the impact of pain on activities of daily living.

At 6 weeks, the true acupuncture treatment arm reported significantly lower BPI worst pain scores than those in the sham acupuncture and the waitlist control arms. The mean BPI worst pain for the true acupuncture arm was 0.92 points lower than the sham acupuncture arm (P = .01) and 0.96 points lower than the waitlist control arm (P = .01). The proportion of patients experiencing a large reduction in BPI worst pain (greater than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively. The differences continued to remain statistically significant at 24 weeks, even though the treatment only continued for 12 weeks.

Associated adverse effects were minimal with true and sham acupuncture and limited to grade 1 bruising.

The cost of the 12-week intervention was about $1,250 or $65-$75 a session. “We feel that there is now sufficient evidence to support insurance coverage of acupuncture of AI arthralgia.”

In a discussion of the paper, Dr. Anne Partridge, from the Dana Farber Cancer Center, noted that it is imperative to seek new ways to improve outcomes in breast cancer, and AIs are contributing to that. However, she echoed the concern that nonadherence to treatment is a “tremendous problem” and hampers the clinical effectiveness of AI therapy.

The rate of discontinuation during the first year of therapy is 20% within the first year and up to 40% of patients do not take them daily. Both early discontinuation and nonadherence contribute to mortality.

Based on these results from the largest randomized controlled trial looking at acupuncture in this setting, should physicians be recommending acupuncture to patients prescribed AI therapy?

“The short answer is, why not?” said Dr. Partridge, “And that we should be recommending it for some of our patients.”

However, there are a number of issues that need to be addressed, she added. The duration of treatment is not known, and the need for follow-up treatment or the frequency of it is not known. The generalizability of it is also unclear when looking at a larger population, and acupuncture is highly operator dependent.

“There are cost and access issues, and insurance right now offers very limited coverage,” she said.

Importantly, Dr. Partridge emphasized, “We know that it will help symptoms, but will it improve adherence to AI?”

It may improve adherence for some patients, but “side effects are only one factor,” she said. “Adherence behavior is complicated. We need to figure out how to optimize these therapies in our patients.”

This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.

SOURCE: Hershman et al. Abstract GS4-04

SAN ANTONIO – Acupuncture significantly reduced joint pain that was associated with the use of aromatase inhibitors (AIs) in women with early breast cancer, according to new findings reported at the San Antonio Breast Cancer Symposium.

The randomized, phase 3 SWOG S1200 clinical trial found that, compared with sham acupuncture and a control group receiving no therapy, women receiving acupuncture reported significantly lower scores on the Brief Pain Inventory–Short Form (BPI).

“We have shown consistently, with multiple measures assessing pain and stiffness, that true acupuncture generated better outcomes than either control group in a large multicenter trial,” said lead author Dawn L. Hershman, MD, leader of the Breast Cancer Program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia University Medical Center. “Acupuncture provides a nonpharmacologic option that can improve symptoms and possibly increase AI adherence and subsequent breast cancer outcomes.”

AIs can reduce both early breast cancer recurrence and mortality. Dr. Hershman noted that these agents are effective in the adjuvant setting and for prevention “but we know that it doesn’t work if you don’t take it. Noncompliance is a major problem among women taking hormonal therapy.”

Noncompliance is multifactorial and one of the main reasons women discontinue their therapy early is because of arthralgias or joint discomfort. “We were interested in a nonpharmacologic intervention, to assess whether or not we could control these symptoms.”

Dr. Hershman pointed out acupuncture provides a safe and effective alternative for patients reluctant to take a prescription medication that can result in other side effects. “Identification of nonopioid options for pain control is a public health priority,” she said.

Acupuncture is a popular nonpharmacologic modality and widely used for a number of indications. Several single-institution studies have suggested that it may be useful for controlling AI-associated arthralgias, while other studies have not demonstrated a benefit.

In this trial, the authors evaluated the efficacy of acupuncture, compared with sham acupuncture or waitlist control, in the treatment of AI associated arthralgia in a large population of patients. The study was conducted at 11 centers.

The cohort comprised 226 postmenopausal women diagnosed with early-stage, hormone receptor–positive breast cancer who were receiving treatment with AIs. The primary endpoint was the decline in joint pain as measured by BPI-SF at 6 weeks, and to assess the duration of the effect, the women were followed for an additional 12 weeks.

Within this group, 110 were randomized to true acupuncture; 59 to sham acupuncture, and 57 to waitlist control (no treatment). Patients receiving true or sham acupuncture had sessions three times a week for 6 weeks followed by one session per week for 6 more weeks. Pain status was reported at baseline, during treatment, and then afterwards, using a variety of measurement tools including the BPI-SF, which is a self-administered 14-item questionnaire that evaluates pain severity on a 0-10 scale, and the impact of pain on activities of daily living.

At 6 weeks, the true acupuncture treatment arm reported significantly lower BPI worst pain scores than those in the sham acupuncture and the waitlist control arms. The mean BPI worst pain for the true acupuncture arm was 0.92 points lower than the sham acupuncture arm (P = .01) and 0.96 points lower than the waitlist control arm (P = .01). The proportion of patients experiencing a large reduction in BPI worst pain (greater than 2) was significantly greater in the true acupuncture arm, compared with the other groups: 58% versus 33% percent and 31%, respectively. The differences continued to remain statistically significant at 24 weeks, even though the treatment only continued for 12 weeks.

Associated adverse effects were minimal with true and sham acupuncture and limited to grade 1 bruising.

The cost of the 12-week intervention was about $1,250 or $65-$75 a session. “We feel that there is now sufficient evidence to support insurance coverage of acupuncture of AI arthralgia.”

In a discussion of the paper, Dr. Anne Partridge, from the Dana Farber Cancer Center, noted that it is imperative to seek new ways to improve outcomes in breast cancer, and AIs are contributing to that. However, she echoed the concern that nonadherence to treatment is a “tremendous problem” and hampers the clinical effectiveness of AI therapy.

The rate of discontinuation during the first year of therapy is 20% within the first year and up to 40% of patients do not take them daily. Both early discontinuation and nonadherence contribute to mortality.

Based on these results from the largest randomized controlled trial looking at acupuncture in this setting, should physicians be recommending acupuncture to patients prescribed AI therapy?

“The short answer is, why not?” said Dr. Partridge, “And that we should be recommending it for some of our patients.”

However, there are a number of issues that need to be addressed, she added. The duration of treatment is not known, and the need for follow-up treatment or the frequency of it is not known. The generalizability of it is also unclear when looking at a larger population, and acupuncture is highly operator dependent.

“There are cost and access issues, and insurance right now offers very limited coverage,” she said.

Importantly, Dr. Partridge emphasized, “We know that it will help symptoms, but will it improve adherence to AI?”

It may improve adherence for some patients, but “side effects are only one factor,” she said. “Adherence behavior is complicated. We need to figure out how to optimize these therapies in our patients.”

This study was supported by the National Institutes of Health National Center for Complementary and Integrative Health and the Office of Research on Women’s Health, and grants from the NIH/National Cancer Institute Division of Cancer Prevention. Dr. Hershman declared no conflicts of interest. Dr. Partridge had no disclosures.

SOURCE: Hershman et al. Abstract GS4-04

SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.

In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.

The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.

op@frontlinemedcom.com

SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.

In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.

The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.

op@frontlinemedcom.com

SAN ANTONIO – Clinical trials have shown a clear benefit for preventing breast cancer recurrence with aromatase inhibitor (AI) therapy following 5 years of tamoxifen. Yet the optimal duration for additional AI therapy following 5 years of endocrine therapy with tamoxifen, an AI, or sequential therapies is not known, according to Michael Gnant, MD, from the Medical University of Vienna.

In the ABCSG-16 trial, Dr. Gnant and his colleagues reported that 5 years of additional therapy with anastrozole (Arimidex) was no more effective than 2 additional years following the standard 5 years of initial endocrine therapy in postmenopausal women with hormone receptor–positive (HR+) breast cancer.

In this video interview at the San Antonio Breast Cancer Symposium, Dr. Gnant notes that, although some patients may still benefit from 5 years of additional therapy, the trial results suggest that most patients can be spared from such adverse events as risk for fractures associated with three additional and evidently unnecessary years of therapy.

The ABCSG-16 study was supported by AstraZeneca. Dr. Gnant disclosed research funding, honoraria, and travel funding from the company and others.

op@frontlinemedcom.com

SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.

Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.

“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.

The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.

“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.

However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.

“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.

POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.

Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.

For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.

Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.

The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.

For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).

The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.

SOURCE: Robertson J et al., Abstract GS1-03

SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.

Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.

“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.

The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.

“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.

However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.

“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.

POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.

Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.

For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.

Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.

The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.

For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).

The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.

SOURCE: Robertson J et al., Abstract GS1-03

SAN ANTONIO – Skip the perioperative aromatase inhibitor (AI) therapy in women with early stage hormone receptor-positive breast cancer, because it doesn’t make a difference in either time to recurrence or overall survival, British investigators advise.

Among nearly 4,500 women enrolled in the POETIC trial, time to recurrence (TTR) and overall survival (OS) were similar whether patients received AI therapy within 2 weeks of surgery or did not, reported John Robertson, MD, from the University of Nottingham, England, and his colleagues.

“There is no evidence of improved clinical outcome with perioperative aromatase inhibitor therapy,” he said at the San Antonio Breast Cancer Symposium.

The trial wasn’t all for naught, however, because it also provided further evidence that measuring Ki67 levels at baseline and at 2 weeks of therapy offer significant and independent prognostic information.

“If your baseline Ki67 is low, the prognosis is good, suggesting no need for 2 weeks of AI treatment and a second Ki67 measurement,” Dr. Robertson said.

However, if the Ki67 level is 10% or higher at baseline, a Ki67 measure after 2 weeks of AI therapy can be used to guide additional therapy.

“If the 2-week Ki67 is low, patients will do relatively well, with 8.4% recurrences, and may need no additional treatment beyond standard of care. If, however, your Ki67 at 2 weeks remains high, you have a poor prognosis with an almost 20% 5-year recurrence risk, and those patients should be considered for additional chemotherapy, and/or for trials looking at new agents,” he said.

POETIC was a randomized phase 3 trial in postmenopausal women with newly diagnosed estrogen– and progesterone receptor–positive invasive breast cancer. Patients were randomized on a 2:1 basis, respectively, to either perioperative therapy with an AI (letrozole or anastrozole) for 2 weeks, surgery, and an additional 2 weeks of AI treatment, or to surgery with no perioperative therapy within a 2-week window. Patients could receive further treatment in accordance with local practice.

Of 4,486 patients randomized, 4,480 were available for analysis, including 2,528 with both baseline and 2-week Ki67 in the perioperative therapy arm, and 678 with paired Ki67 readings in the no-therapy arm.

For the primary endpoint of TTR, the curves were superimposable, with 5-year TTR of 90.9% in the perioperative AI groups, and 90.3% in the no perioperative AI group, translating into an absolute difference of only 0.52%.

Similarly, there were no differences in OS at 5 years, at 89.0% vs. 89.5%, respectively (absolute difference, 0.51%), with survival curves virtually indistinguishable from one another.

The events contributing to TTR, including local or distant recurrence and breast cancer deaths were equally distributed between the trial arms.

For patients with high baseline Ki67 values (10% or greater) at both baseline and after 2 weeks of perioperative AI therapy, the 5-year absolute risk for recurrence was 19.6%, compared with 8.9% for those with high baseline but low 2-week Ki67 levels, and 4.5% for those with low levels at both time points. The hazard ratio for patients with high Ki67 at both time points was 2.22 (P less than .001).

The POETIC trial was supported by Cancer Research UK. Dr. Robertson did not report disclosure information.

SOURCE: Robertson J et al., Abstract GS1-03

SAN ANTONIO – Increasing the dose intensity of adjuvant chemotherapy for breast cancer by spacing cycles more closely or by giving drugs sequentially instead of concurrently improves outcomes, confirms a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Study details

“We know that adjuvant chemotherapy can really help reduce recurrence and prevent breast cancer death. It reduces breast cancer death by about a third,” Mr. Gray noted, giving some background to the analysis. “We are still looking at ways to improve that even further. One of the approaches, which is based on cytokinetic modeling, is to try and increase the dose intensity of the chemotherapy.”

For the meta-analysis, the investigators identified trials that achieved dose intensification by reducing the interval between treatment cycles (a dose-dense approach) and/or by giving drugs sequentially rather than concurrently (allowing delivery of higher doses of each drug).

In all, seven trials, which included 10,004 women in total, tested chemotherapy given every 2 weeks (dose-dense chemotherapy) versus the same chemotherapy given every 3 weeks. Results showed that the former approach netted significantly lower risks of recurrence (rate ratio [RR], 0.83; P = .00004) and breast cancer mortality (RR, 0.86; P = .004), Mr. Gray reported. Absolute gains at 10 years were 4.3% and 2.8%, respectively. Findings were similar after adding five more trials, with another 5,508 women, that had some differences in chemotherapy treatments between arms.

Six trials, which included 11,028 women in total, tested sequential chemotherapy every 3 weeks versus concurrent chemotherapy every 3 weeks. Results showed similarly that the former strategy yielded lower risks of recurrence (RR, 0.87; P = .0006) and breast cancer death (RR, 0.89; P = .03). Absolute gains at 10 years were 3.2% and 2.1%, respectively.

Another six trials, which included a total of 6,532 women, tested sequential chemotherapy given every 2 weeks versus concurrent chemotherapy given every 3 weeks. Results here showed once again that the former yielded lower risks of recurrence (RR, 0.82; P = .0001) and breast cancer mortality (RR, 0.82; P = .001). Absolute gains at 10 years were 4.5% and 3.9%, respectively.

Finally, a pooled analysis of all trials showed that dose intensification reduced the risk of recurrence (RR, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001). Absolute gains at 10 years were 3.6% and 2.7%, respectively.

“That 13% reduction in breast cancer mortality may seem relatively modest, but given that taxane and anthracycline on a standard schedule reduces your chance of breast cancer death by a third, if you then reduce that by another 15%, then you have got almost 50% of breast cancer deaths by dose-dense taxane and anthracycline chemotherapy,” Mr. Gray pointed out. “So these little step-by-step improvements, it’s really important to identify them, and you get incremental gains which result in breast cancer deaths being about half of what they were 25 or 30 years ago.”

The proportional reduction in risk was similar whether tumors were ER positive or negative, but additional follow-up, especially for the positive tumors, will be important. “We do need longer follow-up in these trials, and sadly, many of the funding bodies are not providing funding for long-term follow-up,” he commented. “This is really valuable information, and we should be following these women up further, out to 20 years, given the long natural history of breast cancer.”

In terms of safety, the dose-intensification strategies were actually associated with lower risks of death without recurrence (RR, 0.85; P less than .02) and all-cause mortality (RR, 0.87; P less than .00001). Findings were similar when analyses focused on the first year of treatment.

Tolerability and toxicities of dose-intense regimens relative to standard regimens were not evaluated by the meta-analysis because these outcomes were reported differently across trials, according to Mr. Gray. However, the investigators did perform a systematic review of health-related quality of life studies that will be part of the final manuscript.

“We found surprisingly little extra toxicity” with the dose intensification, he reported. “It’s not very much considering the extra benefits we are getting. And when you know you are getting more benefit, it makes it easy to tolerate a drug.”

“In the U.S., people have moved toward the accelerated chemotherapy much more than they have in Europe. I think people have the mindset, ‘Well, we’ve always done it this way,’ ” Mr. Gray concluded. “This evidence being so clear and definite will help change that mindset. I wouldn’t be surprised if practice in the U.K. and many other parts of Europe doesn’t switch as a result of these very definite findings.” 

SAN ANTONIO – Increasing the dose intensity of adjuvant chemotherapy for breast cancer by spacing cycles more closely or by giving drugs sequentially instead of concurrently improves outcomes, confirms a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Study details

“We know that adjuvant chemotherapy can really help reduce recurrence and prevent breast cancer death. It reduces breast cancer death by about a third,” Mr. Gray noted, giving some background to the analysis. “We are still looking at ways to improve that even further. One of the approaches, which is based on cytokinetic modeling, is to try and increase the dose intensity of the chemotherapy.”

For the meta-analysis, the investigators identified trials that achieved dose intensification by reducing the interval between treatment cycles (a dose-dense approach) and/or by giving drugs sequentially rather than concurrently (allowing delivery of higher doses of each drug).

In all, seven trials, which included 10,004 women in total, tested chemotherapy given every 2 weeks (dose-dense chemotherapy) versus the same chemotherapy given every 3 weeks. Results showed that the former approach netted significantly lower risks of recurrence (rate ratio [RR], 0.83; P = .00004) and breast cancer mortality (RR, 0.86; P = .004), Mr. Gray reported. Absolute gains at 10 years were 4.3% and 2.8%, respectively. Findings were similar after adding five more trials, with another 5,508 women, that had some differences in chemotherapy treatments between arms.

Six trials, which included 11,028 women in total, tested sequential chemotherapy every 3 weeks versus concurrent chemotherapy every 3 weeks. Results showed similarly that the former strategy yielded lower risks of recurrence (RR, 0.87; P = .0006) and breast cancer death (RR, 0.89; P = .03). Absolute gains at 10 years were 3.2% and 2.1%, respectively.

Another six trials, which included a total of 6,532 women, tested sequential chemotherapy given every 2 weeks versus concurrent chemotherapy given every 3 weeks. Results here showed once again that the former yielded lower risks of recurrence (RR, 0.82; P = .0001) and breast cancer mortality (RR, 0.82; P = .001). Absolute gains at 10 years were 4.5% and 3.9%, respectively.

Finally, a pooled analysis of all trials showed that dose intensification reduced the risk of recurrence (RR, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001). Absolute gains at 10 years were 3.6% and 2.7%, respectively.

“That 13% reduction in breast cancer mortality may seem relatively modest, but given that taxane and anthracycline on a standard schedule reduces your chance of breast cancer death by a third, if you then reduce that by another 15%, then you have got almost 50% of breast cancer deaths by dose-dense taxane and anthracycline chemotherapy,” Mr. Gray pointed out. “So these little step-by-step improvements, it’s really important to identify them, and you get incremental gains which result in breast cancer deaths being about half of what they were 25 or 30 years ago.”

The proportional reduction in risk was similar whether tumors were ER positive or negative, but additional follow-up, especially for the positive tumors, will be important. “We do need longer follow-up in these trials, and sadly, many of the funding bodies are not providing funding for long-term follow-up,” he commented. “This is really valuable information, and we should be following these women up further, out to 20 years, given the long natural history of breast cancer.”

In terms of safety, the dose-intensification strategies were actually associated with lower risks of death without recurrence (RR, 0.85; P less than .02) and all-cause mortality (RR, 0.87; P less than .00001). Findings were similar when analyses focused on the first year of treatment.

Tolerability and toxicities of dose-intense regimens relative to standard regimens were not evaluated by the meta-analysis because these outcomes were reported differently across trials, according to Mr. Gray. However, the investigators did perform a systematic review of health-related quality of life studies that will be part of the final manuscript.

“We found surprisingly little extra toxicity” with the dose intensification, he reported. “It’s not very much considering the extra benefits we are getting. And when you know you are getting more benefit, it makes it easy to tolerate a drug.”

“In the U.S., people have moved toward the accelerated chemotherapy much more than they have in Europe. I think people have the mindset, ‘Well, we’ve always done it this way,’ ” Mr. Gray concluded. “This evidence being so clear and definite will help change that mindset. I wouldn’t be surprised if practice in the U.K. and many other parts of Europe doesn’t switch as a result of these very definite findings.” 

SAN ANTONIO – Increasing the dose intensity of adjuvant chemotherapy for breast cancer by spacing cycles more closely or by giving drugs sequentially instead of concurrently improves outcomes, confirms a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG).

Study details

“We know that adjuvant chemotherapy can really help reduce recurrence and prevent breast cancer death. It reduces breast cancer death by about a third,” Mr. Gray noted, giving some background to the analysis. “We are still looking at ways to improve that even further. One of the approaches, which is based on cytokinetic modeling, is to try and increase the dose intensity of the chemotherapy.”

For the meta-analysis, the investigators identified trials that achieved dose intensification by reducing the interval between treatment cycles (a dose-dense approach) and/or by giving drugs sequentially rather than concurrently (allowing delivery of higher doses of each drug).

In all, seven trials, which included 10,004 women in total, tested chemotherapy given every 2 weeks (dose-dense chemotherapy) versus the same chemotherapy given every 3 weeks. Results showed that the former approach netted significantly lower risks of recurrence (rate ratio [RR], 0.83; P = .00004) and breast cancer mortality (RR, 0.86; P = .004), Mr. Gray reported. Absolute gains at 10 years were 4.3% and 2.8%, respectively. Findings were similar after adding five more trials, with another 5,508 women, that had some differences in chemotherapy treatments between arms.

Six trials, which included 11,028 women in total, tested sequential chemotherapy every 3 weeks versus concurrent chemotherapy every 3 weeks. Results showed similarly that the former strategy yielded lower risks of recurrence (RR, 0.87; P = .0006) and breast cancer death (RR, 0.89; P = .03). Absolute gains at 10 years were 3.2% and 2.1%, respectively.

Another six trials, which included a total of 6,532 women, tested sequential chemotherapy given every 2 weeks versus concurrent chemotherapy given every 3 weeks. Results here showed once again that the former yielded lower risks of recurrence (RR, 0.82; P = .0001) and breast cancer mortality (RR, 0.82; P = .001). Absolute gains at 10 years were 4.5% and 3.9%, respectively.

Finally, a pooled analysis of all trials showed that dose intensification reduced the risk of recurrence (RR, 0.85; P less than .00001) and breast cancer mortality (RR, 0.87; P less than .00001). Absolute gains at 10 years were 3.6% and 2.7%, respectively.

“That 13% reduction in breast cancer mortality may seem relatively modest, but given that taxane and anthracycline on a standard schedule reduces your chance of breast cancer death by a third, if you then reduce that by another 15%, then you have got almost 50% of breast cancer deaths by dose-dense taxane and anthracycline chemotherapy,” Mr. Gray pointed out. “So these little step-by-step improvements, it’s really important to identify them, and you get incremental gains which result in breast cancer deaths being about half of what they were 25 or 30 years ago.”

The proportional reduction in risk was similar whether tumors were ER positive or negative, but additional follow-up, especially for the positive tumors, will be important. “We do need longer follow-up in these trials, and sadly, many of the funding bodies are not providing funding for long-term follow-up,” he commented. “This is really valuable information, and we should be following these women up further, out to 20 years, given the long natural history of breast cancer.”

In terms of safety, the dose-intensification strategies were actually associated with lower risks of death without recurrence (RR, 0.85; P less than .02) and all-cause mortality (RR, 0.87; P less than .00001). Findings were similar when analyses focused on the first year of treatment.

Tolerability and toxicities of dose-intense regimens relative to standard regimens were not evaluated by the meta-analysis because these outcomes were reported differently across trials, according to Mr. Gray. However, the investigators did perform a systematic review of health-related quality of life studies that will be part of the final manuscript.

“We found surprisingly little extra toxicity” with the dose intensification, he reported. “It’s not very much considering the extra benefits we are getting. And when you know you are getting more benefit, it makes it easy to tolerate a drug.”

“In the U.S., people have moved toward the accelerated chemotherapy much more than they have in Europe. I think people have the mindset, ‘Well, we’ve always done it this way,’ ” Mr. Gray concluded. “This evidence being so clear and definite will help change that mindset. I wouldn’t be surprised if practice in the U.K. and many other parts of Europe doesn’t switch as a result of these very definite findings.” 

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.

SAN ANTONIO – For premenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer, the addition of the CDK4/6 inhibitor ribociclib (Kisqali) to endocrine therapy and goserelin was associated with a near doubling in progression-free survival (PFS), improvement in pain scores and a longer time to deterioration of quality of life (Qol) scores, investigators reported.

SAN ANTONIO – A meta-analysis of five trials among 873 premenopausal women with early breast cancer finds that temporarily suppressing ovarian function with a gonadotropin-releasing hormone analog during chemotherapy helps preserve fertility, reducing risk of premature ovarian insufficiency by 62% and nearly doubling the posttreatment pregnancy rate. In an interview at the San Antonio Breast Cancer Symposium, lead investigator Matteo Lambertini, MD, of the Institut Jules Bordet in Brussels, Belgium, discussed subgroup findings, the risk-benefit profile, and appropriate patient selection, as well as avenues for future research in this area.

SAN ANTONIO – A meta-analysis of five trials among 873 premenopausal women with early breast cancer finds that temporarily suppressing ovarian function with a gonadotropin-releasing hormone analog during chemotherapy helps preserve fertility, reducing risk of premature ovarian insufficiency by 62% and nearly doubling the posttreatment pregnancy rate. In an interview at the San Antonio Breast Cancer Symposium, lead investigator Matteo Lambertini, MD, of the Institut Jules Bordet in Brussels, Belgium, discussed subgroup findings, the risk-benefit profile, and appropriate patient selection, as well as avenues for future research in this area.

SAN ANTONIO – A meta-analysis of five trials among 873 premenopausal women with early breast cancer finds that temporarily suppressing ovarian function with a gonadotropin-releasing hormone analog during chemotherapy helps preserve fertility, reducing risk of premature ovarian insufficiency by 62% and nearly doubling the posttreatment pregnancy rate. In an interview at the San Antonio Breast Cancer Symposium, lead investigator Matteo Lambertini, MD, of the Institut Jules Bordet in Brussels, Belgium, discussed subgroup findings, the risk-benefit profile, and appropriate patient selection, as well as avenues for future research in this area.

SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.

Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.

“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”

He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.

“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.

Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.

Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).

In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.

All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.

Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.

The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.

The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.

Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.

The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.

Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”

Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.

Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.

Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets. 

SOURCE: Bardia A et al. Abstract GS1-07.

SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.

Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.

“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”

He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.

“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.

Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.

Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).

In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.

All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.

Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.

The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.

The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.

Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.

The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.

Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”

Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.

Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.

Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets. 

SOURCE: Bardia A et al. Abstract GS1-07.

SAN ANTONIO – A novel antibody drug conjugate has shown promise in metastatic triple-negative breast cancer (TNBC), according to new findings presented at the San Antonio Breast Cancer Symposium.

Sacituzumab govitecan, a novel antibody-drug conjugate, demonstrated significant clinical activity when used as a single agent among patients with relapsed/refractory disease who had already received multiple lines of therapy. The objective response rate in a cohort of more than 100 patients was 34%, and that included 3 complete responses and 34 partial responses.

“Sacituzumab govitecan demonstrated significant single-agent activity in this population,” said lead author Aditya Bardia, MD, of Harvard Medical School and Massachusetts General Hospital Cancer Center.

“Metastatic triple-negative breast cancer is an aggressive disease with a poor prognosis that tends to affect young women,” said Dr. Bardia. “Visceral and brain metastases are very common. Currently there is no single standard chemotherapy for relapsed or refractory metastatic triple-negative breast cancer.”

He noted that the response rates to standard chemotherapy are low and that median progression-free survival is in the range of 2-3 months. The response rate to standard chemotherapy first line and beyond, based on available data, is in the range of 6-15%.

“Consequently, there is a large unmet need in the breast cancer community,” said Dr. Bardia.

Sacituzumab govitecan (IMMU-132) is an antitrophoblastic cell-surface antigen (anti–Trop-2) and humanized antibody-SN-38 conjugate, which is the active metabolite of the topoisomerase I inhibitor irinotecan. Trop-2 is highly expressed in most epithelial cancers, including TNBC. A phase 1/2 basket trial was previously conducted in a cohort with multiple, advanced epithelial cancers and showed encouraging activity.

Dr. Bardia and his group also published preliminary results earlier this year in patients with metastatic TNBC, which showed an objective response rate of 30%, and last year, sacituzumab govitecan was granted Breakthrough Designation by the Food and Drug Administration. In the current study, the authors expanded the cohort and looked at a more defined population (third-line setting or greater in metastatic TNBC).

In this study, 110 patients who had metastatic TNBC (109 female, 1 male) and had received two or more lines of therapy for metastatic disease were enrolled between July 2013 and February 2017. The cohort included 53 patients from the investigators’ previously reported study in metastatic TNBC (n=69 total). As of this study’s cutoff date (June 30, 2017), 66 patients had died, 30 were in long term follow up, and 14 were still on treatment.

All patients were treated at the 10 mg/kg dose level, receiving 14.5 median doses (range, 1-88) over a median duration of 4.9 months. Treatment was administered on day 1 and 8 in a 21 day cycle, until progression or unacceptable toxicity.

Within the cohort of this heavily pretreated group, 41% received sacituzumab govitecan as third-line therapy while 59% received it at fourth line or more. The majority of patients had previously received taxanes or anthracyclines, and of note, 75% had previously received prior platinum, and 17% had previously received checkpoint inhibitors.

The clinical benefit rate, calculated using the rate of complete and partial response and stable disease greater than 6 months, was 45%. Responses were durable, with a median duration of 7.6 months by local assessment and 9.1 months by central review.

The median progression-free survival was 5.5 months (95% confidence interval, 4.8-6.6) and median overall survival was 12.7 months (95% CI, 10.8-13.6). Of the long term responders, nine have been progression free for more than a year, and four for more than 2 years. At the time of data cutoff, 12 responders were still receiving treatment.

Of note, Dr. Bardia said, patients stayed on sacituzumab govitecan longer than they had stayed on their most recent previous therapy.

The authors also conducted an exploratory subset analysis but found no difference in response when looking at age, prior regimens, onset of metastasis, the presence of visceral involvement at study entry, or Trop-2 expression.

Response among patients who had previously received checkpoint inhibitors was 47%, but Dr. Bardia cautions that “these numbers are small.”

Treatment with sacituzumab govitecan was well tolerated overall, with 2 patients discontinuing the drug because of related toxicity, and no antidrug antibodies detected. Grade 3 or greater toxicity included neutropenia (39%), leukopenia (14%), and anemia (10%); the incidence of febrile neutropenia was low (7%). There was a high rate of gastrointestinal related toxicity, but the majority were grade 1-2, and the rate of grade 3-4 “was in the single digits, ranging from 5-8%,” said Dr. Bardia. There were no drug-related deaths.

Given the high unmet medical need among patients with metastatic TNBC, data from this trial is being sent to the FDA to be considered for accelerated approval, and a global confirmatory randomized Phase 3 is now underway. “The ASCENT trial is recruiting in the United States right now,” said Dr. Bardia; this trial will include patients with metastatic TNBC who will receive either sacituzumab govitecan or physician’s choice of standard therapy.

Additional studies including rational combinations are currently being evaluated for metastatic TNBC and other breast cancer subsets. 

SOURCE: Bardia A et al. Abstract GS1-07.