More Bevacizumab Trials to Report Outcomes in San Antonio

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).