medwireNews: The outcomes of treatment-naïve, advanced non-small-cell lung cancer (NSCLC) patients with tumor PD-L1 levels of 1–49% may be better with the combination of chemotherapy and immunotherapy than immunotherapy alone, suggests a pooled analysis by the US FDA.
Speaking at the 2021 ASCO Annual Meeting, Oladimeji Akinboro (US Food and Drug Administration, Silver Spring, Maryland, USA) cautioned that as none of the trials included in the analysis directly compared the two regimens, “in effect making this a cross-trial comparison,” the results should be considered “exploratory and hypothesis-generating.”
Nevertheless, the findings “question the use of [immunotherapy] only regimens as control arms of randomized trials” in this patient population “and suggest that the preferred control arms in such trials may be [chemoimmunotherapy] regimens,” he added.
The researchers pooled data from eight randomized controlled trials supporting the FDA approvals of first-line chemoimmunotherapy (n=6 trials) and immunotherapy alone (n=2) regimens in advanced NSCLC, focusing especially on patients with a tumor PD-L1 score of 1–49% and no EGFR or ALK alterations.
The analysis population included 639 patients who received chemoimmunotherapy and 529 who received immunotherapy alone, reported Akinboro, noting that a greater proportion of patients in the combination than immunotherapy alone group were White (88 vs 69%), current or former smokers (91 vs 81%), and had nonsquamous disease (77 vs 63%).
In this population, chemoimmunotherapy appeared to be associated with better overall survival (OS) than immunotherapy, at a median of 21.4 versus 14.5 months, and a hazard ratio (HR) for death of 0.68 favoring the combination.
Progression-free survival (PFS) was similarly prolonged with the combination than with immunotherapy alone, with respective median durations of 7.7 and 4.2 months, and an HR for progression or death of 0.60.
Subgroup analyses showed results that were generally consistent with the full cohort, with the exception of participants aged at least 75 years, among whom neither treatment appeared to be favored with regard to either OS or PFS.
Discussing the limitations further, Akinboro highlighted that “the safety and tolerability of these regimens” was not compared in this pooled analysis.
“Although the overall survival outcomes we have presented should reflect the composite net benefit of drug efficacy and safety, these results are not prescriptive and not intended to regulate the practice of oncology,” he continued.
Mary Redman (Fred Hutchinson Cancer Research Center, Seattle, Washington, USA), who discussed the results in the session, outlined her “wish list” of analyses for the FDA, including a comparison of chemoimmunotherapy and immunotherapy alone regimens by squamous and nonsquamous histology as well as a comparison of these regimens versus chemotherapy.
She also suggested an analysis including studies that did not lead to FDA approval, which could help to address any potential selection bias.
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