medwireNews: Adding cemiplimab to first-line platinum-doublet chemotherapy significantly improves outcomes for patients with advanced non-small-cell lung cancer (NSCLC), regardless of tumor PD-L1 expression or histology, EMPOWER-Lung 3 study data show.
As a result of meeting predefined overall survival (OS) efficacy criteria, the phase 3 trial was stopped early on the recommendation of the independent data monitoring committee, report Miranda Gogishvili (University Clinic Ltd, Tbilisi, Georgia) and co-authors in Nature Medicine.
Previous research demonstrated the efficacy of the PD-1 inhibitor as a first-line monotherapy in advanced NSCLC patients with PD-L1 expression of 50% or higher, resulting in FDA and EMA approvals for this indication.
In the current study, 466 patients with stage III (14.8%) or IV (85.2%) NSCLC without EGFR, ALK, or ROS1 genomic tumor aberrations were randomly assigned to receive cemiplimab 350 mg (n=312) or placebo (n=154) every 3 weeks for up to 108 weeks each in combination with four cycles of an investigator’s choice of platinum-doublet chemotherapy, followed by pemetrexed maintenance where indicated.
The participants were previously untreated for advanced disease, had an even distribution across PD-L1 expression categories, and were slightly more likely to have nonsquamous versus squamous histology (57.1 vs 42.9%).
After median 16.3 months of follow-up in the cemiplimab arm and 16.7 months in the placebo arm, the researchers found that the risk for death was a significant 29% lower with cemiplimab than with placebo. Median OS was 21.9 months in the former group and 13.0 months in the latter.
Median progression-free survival (PFS) was also significantly longer with cemiplimab versus placebo (8.2 vs 50 months), while the objective response rate (ORR) was significantly higher (43.3 vs 22.7%) and the median response duration significantly longer (15.6 vs 7.3 months).
Furthermore, prespecified subgroup analyses showed a similar pattern of results for each outcome, with the exception of OS in patients with PD-L1 expression below 1%, never smokers, women, and those with brain metastases. However, Gogishvili and team note that these subgroups were “relatively small, overlapping and underpowered for OS assessment.”
They say: “Given that cemiplimab plus chemotherapy showed consistently superior PFS and ORR in all subgroups, longer-term follow-up data are awaited to further inform OS results.”
For patient-reported outcomes, the investigators observed a general trend toward greater improvements in the cemiplimab arm versus placebo, including a significantly greater reduction in pain symptoms.
And “the safety profile was generally consistent with what has been reported for cemiplimab as monotherapy and for platinum-based chemotherapy,” they write.
Grade 3 or worse treatment-emergent adverse events (TEAEs) occurred in 43.6% of the cemiplimab group and 31.4% of the placebo group, most commonly anemia (9.9 vs 6.5%) and neutropenia (5.8 vs 5.9%).
Treatment discontinuation as a result of TEAEs was reported in 5.1% of patients receiving cemiplimab and 2.6% of those given placebo, while TEAEs of any grade that led to death occurred in a respective 6.1% and 7.8%. Just three (1.0%) patients discontinued cemiplimab plus chemotherapy due to an immune-mediated AE and one (0.3%) patient died due to immune-mediated pneumonitis.
Gogishvili et al conclude: “Cemiplimab is only the second anti-PD-1/PD-L1 agent to show efficacy in [advanced] NSCLC as both monotherapy and in combination with chemotherapy for both squamous and non-squamous histologies.”
They also highlight the importance of their findings for patients with locally advanced disease who are not candidates for surgical resection or definitive chemoradiation, and are often treated on the basis of data extrapolated from individuals with stage IV disease.
“Therefore, this study fills a gap in the available evidence that is important for clinical practice and establishes a potential new standard-of-care treatment option for these patients,” the authors write.
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