Cemiplimab Shows Improved PFS, Comparable OS to Pembrolizumab in NSCLC

Cemiplimab may yield more favorable outcomes in patients with non–small cell lung cancer (NSCLC) with high programmed cell death-ligand (PD-L1) expression and no genomic aberrations, compared with pembrolizumab, say findings from a meta-analysis published in Therapeutic Advances in Medical Oncology.

In the absence of a head-to-head trial, the researchers compiled data from randomized controlled trials (RCTs) of the 2 programmed cell death-1 (PD-1)/PD-L1 inhibitors in patients with advanced disease and PD-L1 of at least 50%. Alhough the treatments showed comparable overall survival (OS), cemiplimab was associated with statistically significant improvements in progression-free survival (PFS) and overall response rate (ORR) vs pembrolizumab.

“While each new treatment has provided significant benefits to patients, the clinical evidence base for trials targeting high PD-L1 expression is still evolving and uncertainty remains regarding the most appropriate first-line therapeutic strategies,” wrote the researchers. “Moreover, there are no trials that directly compare the efficacy and safety between these immunotherapies. Such an analysis might help clinicians to optimize immune-oncology monotherapy especially in patients with high PD-L1 expression.”

Data was pulled from 2 pembrolizumab trials—KEYNOTE-024 and KEYNOTE-042—and from the EMPOWER-Lung 1 trial of cemiplimab. The researchers analyzed data from the PD-L1 ≥50% populations, rather than the intent-to-treatment populations, from the EMPOWER-Lung 1 and KEYNOTE-042 trials for efficacy evaluation in order to align with the target population.

At 3 months (HR, 0.81; 95% CI, 0.54-1.19) and 30 months (HR, 0.70; 95% CI, 0.40-1.22), OS with cemiplimab was comparable to that with pembrolizumab, although the researchers noted that at 2 years, more patients receiving cemiplimab were alive, and significantly more were alive without disease progression, compared with patients receiving pembrolizumab. From month 6 (HR, 0.62; 95% CI, 0.15-0.83) through month 30 (HR, 0.32; 95% CI, 0.15-0.68), cemiplimab yielded statistically significant improvements in PFS vs pembrolizumab.

Odds of demonstrating an objective response were also favorable for cemiplimab compared with pembrolizumab (odds ratio, 1.64; 95% CI, 1.04-2.62). Safety between the 2 treatments was comparable, with no evidence of differences in grade 3-5 adverse events (AEs), immune-related AEs, or all-cause discontinuation due to AEs.

In addition to cemiplimab and pembrolizumab, atezolizumab has been approved for this group of patients based on data from the IMpower110 trial; however, this trial was excluded in the current analysis due to an incompatible PD-L1 assay used for patient selection. The MYSTIC trial of durvalumab was also excluded because the treatment is not indicated for monotherapy for advanced NSCLC due to failure to meet the study’s primary end point.

“The current systematic literature review focused only on immune-oncology [IO] monotherapies that were licensed or in the process of being evaluated by the FDA for patients with high PD-L1 expression. Nivolumab monotherapy was excluded since it was not indicated for the target population with high PD-L1 expression, given the unfavorable efficacy results from the CheckMate 026 trial,” the authors concluded. “Future analyses should consider the inclusion of IO combination regimens to assess whether the addition of chemotherapy is beneficial for patients with high PD-L1 expression, as there have been discrepancies in the results from several recently published RCTs and results from indirect comparisons suggest a potential benefit of IO combination regimens for particular subgroups.”

Reference

Freemantle N, Xu Y, Wilson F, et al. Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ≥50%. Ther Adv Med Oncol. Published online June 16, 2022. doi:10.1177/17588359221105024