medwireNews: Overall survival (OS) with first-line chemoimmunotherapy may be similar to that with immunotherapy alone among patients with advanced non-small-cell lung cancer (NSCLC) and PD-L1 expression levels of at least 50%, pooled study data suggest.
The analysis, which was presented at the 2022 ASCO Annual Meeting in Chicago, Illinois, USA, included data from 12 randomized controlled trials that supported FDA approvals of their respective regimens.
Six trials included chemoimmunotherapy regimens that involved pembrolizumab, atezolizumab, or nivolumab plus ipilimumab, and six investigated immunotherapy only with pembrolizumab, atezolizumab, nivolumab, nivolumab plus ipilimumab, or cemiplimab. All regimens were compared with platinum-based doublet chemotherapy.
Oladimeji Akinboro, from the US Food and Drug Administration in Silver Spring, Maryland, USA, reported that the 12 trials included 3189 patients who were mostly male (69%) and White (80%). None of the participants carried EGFR mutations or ALK alterations and all had a PD-L1 tumor proportion score of 50% or higher.
After adjusting for age, sex, race, ECOG performance status, histology, and smoking status, Akinboro and team found that there was no significant difference in OS between the patients who received chemoimmunotherapy and those who received immunotherapy only, at a median of 25.0 versus 20.9 months.
Median progression-free survival (PFS), however, was significantly longer in the chemoimmunotherapy arm than in the immunotherapy arm, at 9.6 versus 7.1 months and a hazard ratio of 0.69 in favor of chemoimmunotherapy.
The objective response rate (ORR) was also significantly better with chemoimmunotherapy than with immunotherapy alone, at 61% versus 43% and an odds ratio of 1.2.
Subgroup analyses indicated that most people had a tendency for better OS with chemoimmunotherapy than with immunotherapy alone, but the differences were not statistically significant.
The only exception was for patients aged 75 years and older who had a nonsignificantly better OS when treated with immunotherapy only than when given chemoimmunotherapy.
Discussing the limitations of the study, Akinboro said that the analysis did not examine factors that may explain the discordance between OS and PFS or ORR such as subsequent receipt of platinum-based chemotherapy by patients in the immunotherapy-only arm, which he noted could have attenuated the difference between the two arms.
Differences in safety and tolerability between the two regimens were also not assessed and Akinboro said that if there was a higher rate of death or discontinuation due to toxicity in the chemoimmunotherapy arm this could also have attenuated any OS differences between the two arms.
The presenter stressed that the analysis was an exploratory, hypothesis-generating cross-trial comparison and that the discordant OS and PFS findings warrant further investigation.
He added that the data are “not meant to be prescriptive” but instead “reinforce and emphasize the importance of shared decision-making between patients and their oncologists.”
Discussing the findings, Sukhmani Padda, from Cedars-Sinai Medical Center in Los Angeles, California, USA, said that the data show that “optimal treatment with chemoimmunotherapy versus immunotherapy in PD-L1 high expressers is not known,” and agreed that “we have to have ongoing shared decision-making with our patients.”
She also pointed out that only 10% of study participants were aged 75 years and older, which “is a reminder to us who are designing clinical trials to ensure that our eligibility is modernized and that we are even conducting dedicated trials in this population.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group