No overall benefit seen with bisphosphonate treatment in chemoresistant breast cancer

SAN ANTONIO – Adjuvant zoledronate failed to improve outcomes in breast cancer patients with residual tumor following neoadjuvant chemotherapy in a large, randomized, phase-3 trial, Dr. Gunter von Minckwitz reported at the San Antonio Breast Cancer Symposium.

There was, however, a bright spot buried within the results of the Neo-Adjuvant Trial Add-On (NATAN) trial: the subset of participants over age 55 years showed a 17% improvement in disease-free survival compared with controls. Although this difference didn’t reach statistical significance because of limited patient numbers, it was closely similar to the benefit seen for adjuvant bisphosphonate therapy in the Early Breast Cancer Trialists Collaborative Group’s practice-changing meta-analysis presented earlier at the San Antonio symposium.

That meta-analysis, presented by Dr. Robert Coleman of the University of Sheffield (England), included more than 17,000 participants in randomized trials. The conclusion was that adjuvant bisphosphonate therapy was of significant benefit in postmenopausal breast cancer patients, with a 17% reduction in the risk of mortality and a 34% decrease in the risk of bone metastases, compared with controls. Premenopausal patients didn’t benefit from adjuvant bisphosphonate therapy.

"We had discussed doing another bisphosphonate trial, this one to be limited to postmenopausal patients without a pathologic complete response after neoadjuvant chemotherapy, but having seen Robert Coleman’s presentation yesterday we are not very much in favor of that any longer. We have our practice guideline meeting for Germany in January, and I expect that we will give a recommendation to use bisphosphonates in postmenopausal patients, so it makes no sense to do another prospective trial," said Dr. von Minckwitz, chairman of the German Breast Group, Neu-Isenburg, and a gynecologist at the University of Frankfurt.

NATAN was carried out because patients with residual disease after neoadjuvant chemotherapy have a worse prognosis than those with a pathologic complete response, and they have few adjuvant treatment options. The study included 654 patients with residual disease after at least four cycles of neoadjuvant anthracycline/taxane-based chemotherapy. Patients were randomized to a planned 5 years of postsurgical intravenous zoledronate or observation, plus adjuvant endocrine therapy and/or trastuzumab as indicated.

The study was halted early due to futility after a median follow-up of 48 months because of virtually identical event-free survival rates in the two study arms. Women over age 55 years, who comprised one-third of the study population, were the only subgroup with a strong, albeit nonsignificant, trend toward benefit for zoledronate.

There is a clear need for new treatment options for women with residual tumor after neoadjuvant chemotherapy, particularly those who aren’t postmenopausal. Several novel agents are now in clinical trials in patients with chemoresistant breast cancer, including rucaparib, an oral small-molecule inhibitor of PARP (poly ADP-ribose polymerase), for triple-negative breast cancer; palbociclib, an oral and selective inhibitor of cyclin dependent kinases 4 and 6, in women with hormone receptor–positive/HER2-negative disease; and trastuzumab emtansine, a conjugate of trastuzumab and the cytotoxic agent mertansine, in patients with chemoresistant HER2-positive breast cancer, Dr. von Minckwitz said.

NATAN was funded by Novartis. Dr. von Minckwitz reported having received research grants from, and serving as a speaker and consultant for, Novartis and Roche.

[email protected]

SAN ANTONIO – Adjuvant zoledronate failed to improve outcomes in breast cancer patients with residual tumor following neoadjuvant chemotherapy in a large, randomized, phase-3 trial, Dr. Gunter von Minckwitz reported at the San Antonio Breast Cancer Symposium.

There was, however, a bright spot buried within the results of the Neo-Adjuvant Trial Add-On (NATAN) trial: the subset of participants over age 55 years showed a 17% improvement in disease-free survival compared with controls. Although this difference didn’t reach statistical significance because of limited patient numbers, it was closely similar to the benefit seen for adjuvant bisphosphonate therapy in the Early Breast Cancer Trialists Collaborative Group’s practice-changing meta-analysis presented earlier at the San Antonio symposium.

That meta-analysis, presented by Dr. Robert Coleman of the University of Sheffield (England), included more than 17,000 participants in randomized trials. The conclusion was that adjuvant bisphosphonate therapy was of significant benefit in postmenopausal breast cancer patients, with a 17% reduction in the risk of mortality and a 34% decrease in the risk of bone metastases, compared with controls. Premenopausal patients didn’t benefit from adjuvant bisphosphonate therapy.

"We had discussed doing another bisphosphonate trial, this one to be limited to postmenopausal patients without a pathologic complete response after neoadjuvant chemotherapy, but having seen Robert Coleman’s presentation yesterday we are not very much in favor of that any longer. We have our practice guideline meeting for Germany in January, and I expect that we will give a recommendation to use bisphosphonates in postmenopausal patients, so it makes no sense to do another prospective trial," said Dr. von Minckwitz, chairman of the German Breast Group, Neu-Isenburg, and a gynecologist at the University of Frankfurt.

NATAN was carried out because patients with residual disease after neoadjuvant chemotherapy have a worse prognosis than those with a pathologic complete response, and they have few adjuvant treatment options. The study included 654 patients with residual disease after at least four cycles of neoadjuvant anthracycline/taxane-based chemotherapy. Patients were randomized to a planned 5 years of postsurgical intravenous zoledronate or observation, plus adjuvant endocrine therapy and/or trastuzumab as indicated.

The study was halted early due to futility after a median follow-up of 48 months because of virtually identical event-free survival rates in the two study arms. Women over age 55 years, who comprised one-third of the study population, were the only subgroup with a strong, albeit nonsignificant, trend toward benefit for zoledronate.

There is a clear need for new treatment options for women with residual tumor after neoadjuvant chemotherapy, particularly those who aren’t postmenopausal. Several novel agents are now in clinical trials in patients with chemoresistant breast cancer, including rucaparib, an oral small-molecule inhibitor of PARP (poly ADP-ribose polymerase), for triple-negative breast cancer; palbociclib, an oral and selective inhibitor of cyclin dependent kinases 4 and 6, in women with hormone receptor–positive/HER2-negative disease; and trastuzumab emtansine, a conjugate of trastuzumab and the cytotoxic agent mertansine, in patients with chemoresistant HER2-positive breast cancer, Dr. von Minckwitz said.

NATAN was funded by Novartis. Dr. von Minckwitz reported having received research grants from, and serving as a speaker and consultant for, Novartis and Roche.

[email protected]

SAN ANTONIO – Adjuvant zoledronate failed to improve outcomes in breast cancer patients with residual tumor following neoadjuvant chemotherapy in a large, randomized, phase-3 trial, Dr. Gunter von Minckwitz reported at the San Antonio Breast Cancer Symposium.

There was, however, a bright spot buried within the results of the Neo-Adjuvant Trial Add-On (NATAN) trial: the subset of participants over age 55 years showed a 17% improvement in disease-free survival compared with controls. Although this difference didn’t reach statistical significance because of limited patient numbers, it was closely similar to the benefit seen for adjuvant bisphosphonate therapy in the Early Breast Cancer Trialists Collaborative Group’s practice-changing meta-analysis presented earlier at the San Antonio symposium.

That meta-analysis, presented by Dr. Robert Coleman of the University of Sheffield (England), included more than 17,000 participants in randomized trials. The conclusion was that adjuvant bisphosphonate therapy was of significant benefit in postmenopausal breast cancer patients, with a 17% reduction in the risk of mortality and a 34% decrease in the risk of bone metastases, compared with controls. Premenopausal patients didn’t benefit from adjuvant bisphosphonate therapy.

"We had discussed doing another bisphosphonate trial, this one to be limited to postmenopausal patients without a pathologic complete response after neoadjuvant chemotherapy, but having seen Robert Coleman’s presentation yesterday we are not very much in favor of that any longer. We have our practice guideline meeting for Germany in January, and I expect that we will give a recommendation to use bisphosphonates in postmenopausal patients, so it makes no sense to do another prospective trial," said Dr. von Minckwitz, chairman of the German Breast Group, Neu-Isenburg, and a gynecologist at the University of Frankfurt.

NATAN was carried out because patients with residual disease after neoadjuvant chemotherapy have a worse prognosis than those with a pathologic complete response, and they have few adjuvant treatment options. The study included 654 patients with residual disease after at least four cycles of neoadjuvant anthracycline/taxane-based chemotherapy. Patients were randomized to a planned 5 years of postsurgical intravenous zoledronate or observation, plus adjuvant endocrine therapy and/or trastuzumab as indicated.

The study was halted early due to futility after a median follow-up of 48 months because of virtually identical event-free survival rates in the two study arms. Women over age 55 years, who comprised one-third of the study population, were the only subgroup with a strong, albeit nonsignificant, trend toward benefit for zoledronate.

There is a clear need for new treatment options for women with residual tumor after neoadjuvant chemotherapy, particularly those who aren’t postmenopausal. Several novel agents are now in clinical trials in patients with chemoresistant breast cancer, including rucaparib, an oral small-molecule inhibitor of PARP (poly ADP-ribose polymerase), for triple-negative breast cancer; palbociclib, an oral and selective inhibitor of cyclin dependent kinases 4 and 6, in women with hormone receptor–positive/HER2-negative disease; and trastuzumab emtansine, a conjugate of trastuzumab and the cytotoxic agent mertansine, in patients with chemoresistant HER2-positive breast cancer, Dr. von Minckwitz said.

NATAN was funded by Novartis. Dr. von Minckwitz reported having received research grants from, and serving as a speaker and consultant for, Novartis and Roche.

[email protected]