The combination of the cyclin-dependent kinase 4/6 inhibitor palbociclib plus fulvestrant was approved by the FDA for women with hormone receptor-positive, HER2-negative advanced-stage or metastatic breast cancer in 2016, on the basis of a significant increase in progression-free survival (PFS) versus placebo plus fulvestrant observed in the PALOMA-3 trial. Newly published data reveal the overall survival (OS) outcomes of patients in this cohort.
At a median follow-up duration of 44.8 months, patients receiving palbociclib plus fulvestrant had a median OS duration of 34.9 months versus 28.0 months in the placebo plus fulvestrant group (HR 0.81, 95% CI 0.64–1.03; P = 0.09). These results, although not statistically significant, support the previous observation of an improvement in PFS of 6.6 months reported in 2016. The investigators attributed the lack of a significant improvement in OS in part to the commercial availability of palbociclib, which 18% of patients who had disease progression on placebo subsequently received.
Patients receiving palbociclib plus fulvestrant had a similar profile of adverse events to those reported in the previous analysis, including grade ≥3 neutropenia in 69.6% and grade ≥3 leukopenia in 38.3%.
Prespecified subgroup analyses demonstrated that women who remained sensitive to the previous line of endocrine therapy derived the highest level of benefit from palbociclib; whereas women with intrinsically endocrine resistant disease were less likely to benefit.
These findings confirm that the beneficial improvements in PFS duration are, to an extent, retained as improvements in OS with longer follow-up monitoring. However, as noted by the authors, owing to difficulties in investigating effects on OS in a cohort of patients who are likely to survive, and receive other treatments for a duration that exceeds the trial follow-up period, data from a larger cohort of patients, or from other sources, are likely to be required to demonstrate a statistically significant improvement in OS.
Turner, N. C. et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa1810527 (2018)
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Sidaway, P. Survival data from PALOMA-3 reported. Nat Rev Clin Oncol 15, 725 (2018). https://doi.org/10.1038/s41571-018-0125-9