CHICAGO, IL—The phase 3 PALOMA-3 registration study found that combining the investigational targeted agent palbociclib with fulvestrant improved progression-free survival in women with hormone receptor-positive, HER2-negative advanced breast cancer that had progressed on prior endocrine therapy, a study presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting concluded.

The trial was stopped early based on efficacy seen in the interim analysis.

“Palbociclib was well tolerated and the combination of palbociclib and fulvestrant is an effective treatment option for women whose cancer has progressed on prior endocrine therapy,” said Nicholas C. Turner, MBBS, PhD, a consultant medical oncologist at The Royal Marsden, London & Surrey, UK, and a team leader at The Institute of Cancer Research in London, UK.

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“With palbociclib, we’ve demonstrated efficacy across all prespecified subgroups, including in both pre- and postmenopausal women,” he said. PALOMA-3 is one of the first registration targeted therapy—hormone therapy combination studies in advanced breast cancer to include younger, premenopausal women.

Palbociclib, a novel, first-in-class oral drug, blocks cyclin-dependent kinases (CDKs) 4 and 6. Both CDK4 and CDK6 are among key proteins known to fuel the growth of hormone receptor-positive breast tumors.

Based on strong preclinical evidence that supports combining CDK4 and CDK6 inhibitors with hormonal therapy, fulvestrant, one of the most active hormone therapies for patients with hormone receptor-positive/HER2-negative advanced breast cancer was selected for this trial.

The study randomly assigned 521 women with hormone receptor-positive/HER2-negative advanced metastatic breast cancer whose cancer had relapsed or progressed on prior endocrine therapy 2:1 to oral palbociclib 125 mg/day for 3 weeks followed by 1 week off and fulvestrant 500 mg, per standard of care (347 patients), or placebo and fulvestrant (174 patients). Pre- and perimenopausal women also received goserelin.

Baseline characteristics were well balanced. The median age was 57 and 56 years, 79% were postmenopausal, 60% had visceral disease, and 79% were sensitive to prior endocrine therapy

One previous line of chemotherapy for metastatic disease was permitted. The primary end point was investigator assessed progression-free survival. Secondary end points included overall survival, response assessment, patient-reported outcomes, and safety and tolerability. A preplanned interim analysis was performed after 195 progression-free survival events by an independent data monitoring committee.

At the time of the interim analysis, the study met its primary end point. Median progression-free survival was 9.2 months for palbociclib with fulvestrant and 3.8 months for placebo plus fulvestrant (HR=0.422; 95% CI: 0.318, 0.560, P<0.000001).

Consistent benefit from palbociclib was seen in pre- and postmenopausal women.

The most common adverse events (AEs) for palbociclib + fulvestrant compared with placebo + fulvestrant were neutropenia (79% vs, 3%, respectively), leucopenia (46% vs. 4%, respectively), and fatigue (38% vs. 27%, respectively).

Febrile neutropenia was reported in 0.6% of patients on palbociclib + fulvestrant and 0.6% of patients on placebo + fulvestrant. The discontinuation rate due to adverse events was 2.6% on palbociclib and 1.7% on placebo. There were no deaths due to AEs or toxicity.

Longer follow-up is needed to determine the effect of palbociclib on overall survival, Dr. Turner said.

“For women with advanced breast cancer, it’s remarkable to be able to stall disease progression and stave off the need for chemotherapy for months with a simple pill,” said ASCO Expert Don S. Dizon, MD, in a press release. “In one of the most common forms of advanced breast cancer, palbociclib works in both older and younger women.”

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Another study, PALOMA-2, is exploring the efficacy of palbociclib as a therapy for advanced breast cancer not previously treated with hormonal therapy. Dr. Turner noted that researchers are also looking at the possibility of using this therapy in women with early-stage hormone receptor-positive breast cancer.

Earlier this year, the U.S. Food and Drug Administration granted palbociclib accelerated approval for use in combination with letrozole for women with metastatic estrogen receptor positive, HER2-negative breast cancer who have not yet received hormonal therapy for their metastatic disease. The approval was granted based on results of PALOMA-1, a phase 2 study.

The PALOMA-3 results were also published online in the New England Journal of Medicine.1


  1. Turner NC, Ro J, André F, et al. Palbociclib in hormone-receptor–positive advanced breast cancer. N Engl J Med. Published online June 1, 2015.