ASCO 2015: Novel Targeted Drug Palbociclib Slows Progression of Hormone Receptor–Positive Breast Cancer


Key Points

  • Progression-free survival among women with previously treated hormone receptor–positive, HER2-negative advanced breast cancer was 9.2 months for patients receiving palbociclib and fulvestrant vs 3.8 months with placebo and fulvestrant.
  • The phase III study, PALOMA-3, was stopped early based on efficacy seen in the interim analysis.
  • The benefit from palbociclib was demonstrated across all prespecified subgroups, including pre- and postmenopausal women.

Results from the phase III registration study PALOMA-3 show that adding the investigational targeted agent palbociclib (Ibrance) to the standard hormonal therapy fulvestrant (Faslodex) more than doubled the duration of disease control, delaying disease progression by roughly 5 months in women with previously treated, hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. This trial was stopped early based on efficacy seen in the interim analysis.

The lead study author Nicholas C. Turner, MD, PhD, reported the results at the 2015 ASCO Annual Meeting (Abstract LBA502). Dr. Turner is a consultant medical oncologist at The Royal Marsden and a team leader at The Institute of Cancer Research, London.

Blocks Cyclin Dependent Kinases  

Palbociclib is a novel, first-in-class oral drug that blocks cyclin dependent kinases (CDK) 4 and 6. Prior research has shown that CDK4 and CDK6 are among the key proteins that fuel the growth of hormone receptor–positive breast tumors. Strong preclinical evidence supports combining CDK4 and CDK6 inhibitors with hormonal therapy.

“This is the first phase III study to report on with a CDK4/6 inhibitor and identifies and confirms that [CDK4 and CDK6 are key enzymes] to target for hormone receptor–positive breast cancer,” Dr. Turner stated.

Earlier this year, the U.S. Food and Drug Administration granted palbociclib accelerated approval for use in combination with letrozole for postmenopausal women with advanced estrogen receptor–positive, HER2-negative breast cancer as initial endocrine therapy for metastatic disease. The approval was granted based on results of a prior phase II study, PALOMA-1, showing that palbociclib in combination with letrozole significantly improved progression-free survival compared to letrozole alone.

Comparable Benefits for Pre- And Postmenopausal Women

In the PALOMA-3 trial, 521 women were randomly assigned to palbociclib in combination with fulvestrant (n = 347), the standard-of-care endocrine therapy for these women, or placebo in combination with fulvestrant (n = 174). All patients’ cancer had progressed on prior endocrine therapy, and all had received a maximum of one prior chemotherapy regimen for advanced cancer.

Postmenopausal women must have experienced disease progression on prior aromatase inhibitor therapy, and premenopausal women (21% of study participants) had all received goserelin (Zoladex). According to the authors, PALOMA-3 is one of the first registration targeted therapy–hormone therapy combination studies in advanced breast cancer to include younger, premenopausal women.

At the time of this interim analysis, investigator-assessed progression-free survival, the primary endpoint of the study, was 9.2 months for patients receiving palbociclib compared to 3.8 months for patients receiving placebo, “with a hazard ratio of 0.422 and a highly significant P value of < .000001,” Dr. Turner stated. “The curves separate early and then continue to separate with ongoing follow-up,” he added.  

“The benefit from palbociclib was demonstrated across all prespecified subgroups, including pre- and postmenopausal women,” Dr. Turner noted.

Combination Generally Well Tolerated

The palbociclib and fulvestrant combination was generally well tolerated. The most common adverse events reported were hematologic, with neutropenia occurring in 79% of patients in the palbociclib arm vs 3% in the placebo arm, and leukopenia occurring in 46% vs 4%. “The incidence of febrile neutropenia,” Dr. Turner noted, “was very rare—0.6% in both arms.”  

Symptomatic adverse events were largely similar in both groups. There was a small increase in fatigue, alopecia, and infections, in the palbociclib group. Serious adverse events affected 9.6% in the palbociclib group vs 14.0% in the placebo group. Discontinuations due to adverse events were similar, 2.6% with palbociclib vs 1.7% with placebo.

Longer Follow-up Needed

Longer follow-up is needed to determine the effect of palbociclib on overall survival. Quality-of-life data were collected and will be reported at a later date.

“The PALOMA-3 results are incredibly important for women with hormone receptor–positive advanced or metastatic breast cancer and represent a new standard of care option” for women with previously treated hormone receptor–positive, HER2-negative metastatic breast cancer, commented ASCO expert and press briefing moderator Don S. Dizon, MD. The follow-up data on overall survival and quality of life are awaited, he added. Dr. Dizon is Clinical Co-Director of Gynecologic Oncology and Director of the Oncology Sexual Health Clinic at Massachusetts General Hospital, Boston.

Another study known as 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.

The study received funding from Pfizer. Dr. Turner reported honoraria from Roche, Novartis, AstraZeneca, Pfizer, Servier, Clovis Oncology, and Biomarin; and research funding from AstraZeneca, Pfizer, and Roche/Genentech. For full disclosures of the study authors, view the study abstract at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.