ASCO 2015 Report: New, less toxic, treatment emerges for difficult-to-treat breast cancer

by Bruce Sylvester: Investigators from the phase III PALOMA-3 trial report that treatment with the recently FDA-approved drug palbociclib more than doubled the time to cancer recurrence among subjects with hormone-receptor (HR+) positive metastatic breast cancer.

This trial was ended early due to efficacy discovered in the interim analysis.

The investigators presented their findings on May 30, 2015 at ASCO 2015/American Society of Clinical Oncology and published them simultaneously in the New England Journal of Medicine.

“These are women with advanced metastatic cancer whose disease was kept in check without the use of toxic and life-disrupting chemotherapy,” said investigator Massimo Cristofanilli, M.D., Director of the Breast Care Center at the Thomas Jefferson Univerity in Philadelphia, Pennsylvania, USA. “This is a major advance for this population of women for which we had very few active options and are often treated with chemotherapy alone.”

The researchers enrolled women with HR+/HER2- breast cancer, and they randomized the subjects to palbociclib with fulvestrant (345 subjects) or placebo with fulvestrant (172 subjects).

All subjects had metastatic disease which had worsened or relapsed after initial hormonal therapy, and they were not candidates for the HER2-blocking therapy herceptin.

Twenty-one percent were premenopausal.

The study was ended early, at 10 months, because it had met the primary endpoint of improving progression-free survival/time to cancer relapse.

Subjects on palbociclib-plus-fulvestrant achieved a median progression-free survival of 9.2 months, compared to 3.8 months on for subjects on fulvestrant monotherapy.

Progression or recurrence of cancer appeared in 25 percent of palbociclib-plus- fulvestrant treated subjects, compared with 50 percent of patients treated with fulvestrant monotherapy.

Common side effects of palbociclib treatment included neutropenia and leukopenia, effects that show the drug is working. Rates of nausea and fatigue were low. The drug was better tolerated than biologics used in this clinical situation.

“After initial hormonal therapy stops working in metastatic breast cancer, the next step is typically chemotherapy, which can be effective, but the side effects are often very difficult for women,” said investigator Nicholas C. Turner, a consultant medical oncologist at The Royal Marsden Hospital and a team leader at The Institute of Cancer Research, London, United Kingdom. “This relatively easy-to-take new drug can substantially delay the point when women need to start chemotherapy, making this an exciting new approach for women.”

On February 3, 2015, the U. S. Food and Drug Administration/FDA approved palbociclib (Ibrance®) for use in combination with letrozole for the treatment of postmenopausal women with ER-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for metastatic disease.

The study received funding from Pfizer.