medwireNews: PALOMA-2 study findings suggest that first-line palbociclib does not improve overall survival (OS) when added to letrozole for estrogen receptor (ER)-positive, HER2-negative advanced breast cancer, but the analysis was hindered by missing data.
Speaking at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, Richard Finn (University of California, Los Angeles, USA) explained that the primary PALOMA-2 analysis found that adding the CDK4/6 inhibitor to letrozole almost doubled progression-free survival compared with placebo, at a median of 24.8 versus 14.5 months, but OS data were immature at that time.
After a median 90 months of follow-up, the required number of OS events were met (405 deaths in total) and Finn reported the findings at the meeting.
He told delegates that median OS was 53.9 months among the 444 participants randomly assigned to receive oral palbociclib 125 mg/day in a 3 weeks on, 1 week off schedule plus letrozole 2.5 mg/day as a first-line treatment for advanced disease.
This was not significantly different from the median OS of 51.2 months among the 222 participants given placebo plus letrozole.
However, Finn noted that interpretation of the findings “is limited by the large and disproportionate percentage of patients with missing survival data between treatment arms.”
Specifically, 13% of participants in the palbociclib arm and 21% of those in the placebo arm had missing survival data as a result of consent withdrawal or being lost to follow-up.
To address the discordance, the researchers performed an unplanned post-hoc analysis that excluded patients with missing data. In this analysis, median OS was 51.6 months with palbociclib and 44.6 months with placebo, also a nonsignificant difference.
Subgroup analyses suggested that participants with a disease-free interval (DFI) of more than 12 months prior to enrollment derived greater benefit from palbociclib than those with a shorter DFI.
To investigate further, Finn and team combined PALOMA-2 data with data from the earlier PALOMA-1 trial and found that median OS was 64.0 months among patients with a DFI of more than 12 months who received palbociclib and a significantly shorter 44.6 months among those from this subgroup who received placebo, with a hazard ratio of 0.74 in favor of palbociclib.
Of note, discussant Claudine Isaacs, from Georgetown University Medical Center in Washington, DC, USA, said she would “urge caution in the interpretation of the unplanned overall survival analysis that was presented excluding those patients with missing survival data as this analysis has some biases.”
She remarked: “The patients should have been censored as of their last follow-up visit and not excluded entirely.”
The median treatment duration was 22.0 months in the palbociclib arm and 13.8 months in the placebo arm, and Finn noted that there was no evidence of long-term toxicity with palbociclib plus letrozole. At the time of analysis, 10% of patients remained on the combination treatment.
He concluded that although OS findings were not statistically significant, “median survival of over 50 months in this population represents a significant improvement in the natural history of hormone receptor-positive breast cancer.”
He added: “This is highlighted in the subgroup of patients with a disease-free interval of greater than 12 months.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group