PALOMA-3 OS Results Add Support For Palbociclib Use In Advanced Breast Cancer

Overall survival results reported for the phase III PALOMA-3 trial of palbociclib plus fulvestrant in the advanced breast cancer setting

medwireNews: Adding palbociclib to fulvestrant leads to significantly better overall survival (OS) in a subgroup of patients with hormone receptor-positive, HER2-negative advanced breast cancer, specifically those with sensitivity to previous endocrine therapy, trial findings show. 

Although the intention-to-treat (ITT) analysis was not statistically significant, “the addition of palbociclib to fulvestrant resulted in an absolute prolongation of overall survival of 6.9 months”, the PALOMA-3 investigators write in The New England Journal of Medicine

“This result is consistent with the significant prolongation in progression-free survival” that was reported previously, they continue. 

In the ITT population of the phase III trial, median OS was 34.9 months for the 347 patients who were randomly allocated to receive the CDK4/6 inhibitor at a dose of 125 mg/day for 3 weeks of every 4-week cycle alongside fulvestrant and was 28.0 months for the 174 patients who received placebo plus fulvestrant. This gave a nonsignificant hazard ratio (HR) for death of 0.81. 

But when the analysis was restricted to the subgroup of 410 participants who had documented sensitivity to prior endocrine therapy – defined as clinical benefit or treatment continuation for 24 months or more before recurrence – median OS was significantly improved with the addition of palbociclib, at 39.7 months versus 29.7 months with placebo. The absolute between-group difference was 10.0 months and the HR for death was 0.72 favouring palbociclib. 

Patients without sensitivity to endocrine therapy, however, did not derive a significant OS benefit from the addition of palbociclib; the median OS times were 20.2 and 26.2 months in the palbociclib and placebo groups, respectively. But the study authors point out that “relatively few patients with intrinsic endocrine resistance were recruited in the trial, which limits the assessment of palbociclib in these patients.” 

Furthermore, palbociclib use was associated with a significantly longer median time to subsequent therapy and to first use of chemotherapy relative to placebo in an exploratory analysis of the ITT population, at 18.8 versus 14.1 months and 17.6 versus 8.8 months, respectively. 

And no new safety signals were observed in the current analysis, even though the follow-up was longer, at a median of 44.8 months, report Nicholas Turner, from the Institute of Cancer Research and Royal Marsden Hospital in London, UK, and co-authors. 

They note that detecting a significant OS benefit “in the context of a disease in which survival after disease progression is substantially longer than the time in the trial” can be a challenge. Trials need to be “much larger” in this context, say the researchers, which can be difficult. 

They conclude: “Future meta-analyses of CDK4/6 inhibitor studies may provide a more robust assessment of the effect of this class of drugs on overall survival, including in subgroups of patients.” 

These data were simultaneously presented at the ESMO 2018 Congress in Munich, Germany. 



Cristofanilli M, Slamon DJ, Ro J, et al. Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2_) advanced breast cancer (ABC): Analyses from PALOMA-3 . ESMO 2018 Congress, 19-23 October, Munich, Germany (LBA2_PR). 

Turner NC, Slamon DJ, Ro J, et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer . N Engl J Med; Advance online publication 20 October 2018.
doi: 10.1056/NEJMoa1810527

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