medwireNews: PALOMA-3 trial findings show that overall survival (OS) is significantly improved with the addition of the CDK4/6 inhibitor palbociclib to fulvestrant in patients with hormone receptor-positive, HER2-negative advanced breast cancer and sensitivity to prior endocrine therapy.
Speaking to the press at the ESMO 2018 Congress in Munich, Germany, presenting author Massimo Cristofanilli (Feinberg School of Medicine, Chicago, Illinois, USA) noted that although the improvement did not reach statistical significance in the overall trial population, the absolute gain in OS was similar to that previously reported for progression-free survival in this trial.
He continued: “The demonstration of a positive impact on OS […] provides additional confidence to clinicians and patients as to the benefits of this combination as an appropriate and effective treatment approach.”
Over a median follow-up of 44.8 months, the secondary endpoint of OS was a median of 34.9 months for the 347 participants of the double-blind, phase III trial who were randomly assigned to receive daily palbociclib at a dose of 125 mg for 21 days of each 28-day cycle plus fulvestrant.
The median OS for the 174 patients who instead received placebo alongside fulvestrant was 28.0 months, which equated to an absolute difference of 6.9 months, but the hazard ratio (HR) for death of 0.81 was not statistically significant.
However, the OS benefit with palbociclib addition was significant in the prespecified subgroup of patients with sensitivity to previous endocrine therapy, defined as documented clinical benefit or receipt of therapy for at least 24 months before recurrence. Specifically, OS was a median of 39.7 and 29.7 months in the palbociclib and placebo groups, respectively, giving an absolute difference of 10.0 months and a significant HR of 0.72 in favor of palbociclib.
By contrast, the between-group difference was not significant among patients with intrinsic endocrine resistance (median, 20.2 vs 26.2 months in the palbociclib and placebo arms, respectively).
Additionally, an exploratory analysis showed that palbociclib treatment significantly prolonged the time to subsequent therapy (median, 18.8 vs 14.1 months) and also time to first use of chemotherapy (median, 17.6 vs 8.8 months) relative to placebo, indicating that palbociclib “did not interfere with the type or efficacy of standard treatment after progression,” Cristofanilli said.
And he noted that the safety profile of the palbociclib–fulvestrant combination did not change from that seen in the primary analysis, despite the longer follow-up.
In conclusion, Cristofanilli said that these results from the PALOMA-3 trial “confirm the use of palbociclib plus fulvestrant as a standard of care” in previously treated patients with hormone receptor-positive, HER2-negative advanced breast cancer.
These data are simultaneously published in The New England Journal of Medicine.
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