Palbociclib Improves Progression-Free Survival in Advanced Hormone Receptor–Positive Breast Cancer


Key Points

  • Palbociclib significantly improved progression-free survival in women with advanced hormone receptor–positive breast cancer.
  • Similar improvements were observed among premenopausal/perimenopausal women and postmenopausal women.

In a phase III PALOMA 3 trial reported at the 2015 ASCO Annual Meeting and published in The New England Journal of Medicine, Turner et al found that the cyclin-dependent kinase 4 and 6 inhibitor palbociclib (Ibrance) significantly improved progression-free survival in women with advanced hormone receptor–positive/HER2-negative breast cancer that had relapsed or progressed during endocrine therapy.

Study Details

In this double-blind trial, 521 women from 17 countries were randomly assigned 2:1 between October 2013 and August  2014 to receive oral palbociclib at 125 mg/d for 3 weeks followed by 1 week off and fulvestrant at 500 mg intramuscularly every 14 days for the first three injections and then every 28 days (n = 347) or placebo plus fulvestrant (n = 174). Premenopausal/perimenopausal patients received goserelin (Zoladex) for the duration of study treatment, starting ≥ 4 weeks before randomization and continuing every 28 days. The primary endpoint was investigator-assessed progression-free survival.

The palbociclib and placebo groups were generally balanced for baseline characteristics. Overall, median age was 57 years, 60% of patients had visceral disease, 79% were postmenopausal, 79% had cancer that was sensitive to prior endocrine therapy, 67% had both estrogen receptor–positive and progesterone receptor–positive disease, 27% had estrogen receptor–positive and progesterone receptor-negative disease, 78% had measurable disease, 23% had at least partially lytic bone-only disease, and 23% had metastatic disease as first disease manifestation (including 25% of palbociclib and 21% of placebo patients).

Improved Progression-Free Survival

On preplanned interim analysis, median progression-free survival was 9.2 months in the palbociclib group vs 3.8 months in the placebo group (hazard ratio [HR] = 0.42,  P < .001). Subgroup analysis showed consistent benefit of palbociclib, including among premenopausal/perimenopausal patients and postmenopausal patients (HRs = 0.44 and 0.41; P = 0.94 for interaction).

Objective response rates were 10.4% vs 6.3% (P = .16), and clinical benefit rates were 34.0% vs 19.0% (P < .001). At the time of the progression-free survival interim analysis, overall survival data were immature; a total of 28 patients had died, including 19 (5.5%) in the palbociclib group and 9 (5.2%) in the placebo group.

Adverse Events

The most common grade 3 or 4 adverse events in the palbociclib group were neutropenia (62.0% vs 0.6% in the placebo group), leukopenia (25.2% vs 0.6%), anemia (2.6% vs 1.7%), thrombocytopenia (2.3% vs 0%), and fatigue (2.0% vs 1.2%). Febrile neutropenia occurred in 0.6% of both groups. Adverse events led to treatment discontinuation in 2.6% vs 1.7%.

The investigators concluded: “Among patients with hormone-receptor–positive metastatic breast cancer who had progression of disease during prior endocrine therapy, palbociclib combined with fulvestrant resulted in longer progression-free survival than fulvestrant alone.”

Nicholas C. Turner, MD, PhD, of the Royal Marsden Hospital and Institute of Cancer Research, is the corresponding author for the New England Journal of Medicine article.

The study was funded by Pfizer. For full disclosures of the study authors, visit

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