Palbociclib Plus Fulvestrant ‘A Therapeutic Option’ For Recurrent, Metastatic Breast Cancer

Results of the phase III PALOMA-3 support the use of palbociclib plus fulvestrant in patients with metastatic breast cancer irrespective of the degree of endocrine sensitivity or PIK3CA mutational status

medwireNews: Addition of palbociclib to fulvestrant significantly extends progression-free survival in women with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer that has progressed after previous endocrine therapy, shows the final analysis of the PALOMA-3 trial.

The benefits of the combination were maintained “irrespective of the degree of endocrine resistance, hormone-receptor expression level, and PIK3CA mutational status”, say Massimo Cristofanilli, from Northwestern University in Chicago, Illinois, USA, and colleagues. They add that palbociclib plus fulvestrant “could be considered as a therapeutic option” for this patient population.

Speaking to the press, study author Nicholas Turner, from the Institute of Cancer Research and Royal Marsden Hospital in London, UK, said: “We hope our results lead to the adoption of this drug combination in breast cancer, where it delays the need to start chemotherapy by an average of nine months.”

After a median follow-up of 8.9 months, progression-free survival (PFS) was a median of 9.5 months for the 347 patients randomly assigned to receive oral palbociclib 125 mg daily for 3 weeks of a 28-day cycle together with fulvestrant. This was significantly longer than the 4.6 months recorded for the 174 women given placebo alongside fulvestrant, and equated to a hazard ratio of 0.46. These findings are in line with those of the interim analysis, conducted after a median follow-up of 5.6 months, say the researchers.

The results of subgroup analyses were “generally consistent” with those of the overall study cohort, they add, with the benefits of palbociclib over placebo maintained regardless of whether patients were sensitive or not to prior hormonal therapy or whether they harboured wild-type or mutated PIK3CA.

Moreover, an objective response was achieved by 24.6% of 268 patients with measureable disease in the palbociclib treatment arm and by 10.9% of 138 patients in the placebo arm, a significant difference. However, the team highlights that responses to the combination of palbociclib plus fulvestrant were “slow to manifest”, with a median time to response of 112 days compared with 57 days for the placebo arm.

Adverse events of grade 3 or 4 occurred more frequently in the palbociclib than in the placebo group, at 73% versus 22%, with neutropenia (65 vs 1%) and leukopenia (28 vs 1%) the most common.

However, the incidence of febrile neutropenia was “similarly low” in both treatment arms and only a small (4%) proportion of palbociclib-treated patients discontinued treatment as a result of toxicity, leading Massimo Cristofanilli et al to comment that the inhibitor of CDK4 and CDK6 has an acceptable safety profile.

And they conclude in The Lancet Oncology: “Our findings confirm the important observation that endocrine monotherapy has limited efficacy in patients with disease progression after previous exposure to endocrine therapy, irrespective of clinical or molecularly defined endocrine sensitivity, suggesting a need for the routine use of more effective combination regimens.”


Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial.Lancet Oncol 2016; Advance online publication 2 March. doi:

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