Dr Simon on PD-L1 Inhibitors in NSCLC

George Simon, MD, FACP, FCCP, executive director, Moffitt Cancer Center-AdventHealth joint Clinical Research Unit, senior member, Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center, discusses findings from an FDA pooled analysis of PD-1/PD-L1 inhibitors with or without chemotherapy in patients with non–small cell lung cancer (NSCLC).

A study evaluated the outcomes with first-line PD-1/PD-L1 inhibitors alone or with chemotherapy in patients with advanced NSCLC. For the analysis, investigators pooled overall survival (OS) and progression-free survival (PFS) data from 12 randomized clinical trials that investigated first-line PD-1/PD-L1 inhibitors with or without chemotherapy in this population.

At the 2021 ASCO Annual Meeting, it was reported that in the subset of patients with a PD-L1 score of 1% to 49%, chemotherapy plus immunotherapy provided significant exploratory PFS and OS benefits compared with immunotherapy alone, Simon explains. The median PFS was 7.7 months (95% CI, 7.1-8.4) with chemotherapy plus immunotherapy vs 4.2 months (95% CI, 4.0-4.9) with immunotherapy alone (HR, 0.60; 95% CI, 0.48-0.76). The median OS was 21.4 months (95% CI, 19.4-25.2) with the combination vs 14.5 months (95% CI, 12.2-16.9) with immunotherapy alone (HR, 0.68; 95% CI, 0.52-0.90).

At the 2022 ASCO Annual Meeting, the study investigators reported findings from the subgroup of patients with a PD-L1 score of at least 50%. Immunotherapy alone is a standard of care for this patient population, and several agents are approved for use in this setting, including pembrolizumab (Keytruda), atezolizumab (Tecentriq), and cemiplimab (Libtayo), Simon notes. Data from this updated analysis showed OS and PFS benefits with chemotherapy plus immunotherapy in the subset of patients with a PD-L1 score of 50% or greater. The median OS was 25.0 months and 20.9 months in the chemotherapy/immunotherapy and immunotherapy arms, respectively (HR, 0.82; 95% CI, 0.62-1.08). The median PFS was 9.6 months and 7.1 months in the chemotherapy/immunotherapy and immunotherapy arms, respectively (HR, 0.69; 95% CI, 0.55-0.87). This survival benefit was seen regardless of ECOG performance status and smoking status.

One subgroup of patients with a PD-L1 score of at least 50% that did not seem to derive significant benefit from the addition of chemotherapy to immunotherapy was those who were at least 75 years of age. In this subgroup, the median OS was not estimable vs 18.9 months in the chemotherapy/immunotherapy and immunotherapy arms, respectively (HR, 1.68; 95% CI, 0.69-4.06), and the median PFS was 11.8 months vs 7.2 months in the chemotherapy/immunotherapy and immunotherapy arms, respectively (HR, 1.22; 95% CI, 0.58-2.57). Patients in this age group with a PD-L1 score of 50% or greater may have better outcomes with immunotherapy alone, Simon concludes.