First-in-class CDK 4/6 inhibitor improves overall survival in advanced breast cancer patients
Final analysis of results from the PALOMA-3 study showed improvement in overall survival (OS) with addition of cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib to fulvestrant in hormone receptor−positive, HER2-negative advanced breast cancer that has relapsed or progressed on hormonal therapy.
The final analysis of the prospective, randomized, phase III PALOMA-3 trial in 521 hormone receptor−positive, HER2-negative advanced breast cancer patients (median follow up, 44.8 months) showed that the median OS improved by 6.9 months with palbociclib plus fulvestrant vs placebo plus fulvestrant (34.9 months [95 percent confidence interval (CI), 28.8 to 40] vs 28 months [95 percent CI, 23.6 to 34.6]; p=0.043). [Cristofanilli M, et al, ESMO 2018, abstract LBA2_PR]
“This is the first report demonstrating that the absolute gain in [overall] survival is similar to the absolute gain in progression-free survival [PFS] in the whole population. This is very important to patients in terms of improving the chance of a long-term life in spite of advanced disease,” reported investigator Professor Massimo Cristofanilli of the Northwestern University, Feinberg School of Medicine, Chicago, US, at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich, Germany.
“The study was unpowered for OS so the data should be cautiously interpreted. Although the results strongly suggest that the PFS benefit may translate into OS benefit, the other trials conducted with CDK4/6 inhibitors will contribute to confirm the estimate of the OS benefit observed in this study,” commented discussant Dr Carmen Criscitiello of the European Institute of Oncology, Milan, Italy.
Findings from the PALOMA-3 trial reported 2 years ago demonstrated that fulvestrant plus palbociclib was associated with significant and consistent improvement in PFS compared with fulvestrant plus placebo irrespective of the degree of endocrine resistance, hormone-receptor expression level, and PIK3CA mutational status. [Lancet Oncol 2016;17:425-439]