Patients with KRAS-mutant non-small cell lung cancer (NCSLC) should receive combination chemotherapy/immune checkpoint inhibitors in the first line, according to research presented at the 2022 ASCO Annual Meeting.

While immune checkpoint inhibitors have improved outcomes in certain NSCLC settings, it was previously unclear whether the presence of targetable mutations limited front-line response to these therapies. In a US Food and Drug Administration (FDA) pooled retrospective analysis, researchers evaluated whether KRAS status affected response to front-line immune checkpoint inhibitors among patients with NSCLC. These findings were presented by Eric C. Nakajima, MD, of the FDA in Silver Spring, Maryland.

Dr Nakajima and colleagues evaluated objective response rates (ORRs) and overall survival (OS) by KRAS mutational status — specifically, whether patients had mutant, G12C, or wild-type status. The evaluated front-line regimens were immune checkpoint inhibitors with chemotherapy, immune checkpoint inhibitors alone, and chemotherapy alone. Subgroups were also analyzed based on patient PD-L1 status.


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Overall, data were included for 1430 patients, of whom 61% had wild-type KRAS, while 39% had mutated KRAS. Of patients with KRAS-mutated disease, 11% had KRAS G12C. In the overall cohort, 60% of patients were men, 60% were positive for PD-L1, and 67% were former or current smokers.

In the KRAS-mutated group, the median OS periods for the combination therapy, immune checkpoint inhibitors only, and chemotherapy only groups were 22.4 months (95% CI, 18.2-not estimable), 16.2 months (95% CI, 11.1-not estimable), and 17.1 months (95% CI, 12.3-18.9), respectively; ORRs were 46%, 37%, and 35%, respectively.

In the KRAS G12C mutation group, the median OS periods for the combination therapy, immune checkpoint inhibitors only, and chemotherapy only groups were 20.8 months (95% CI, 11.3-not estimable), 11.8 months (95% CI, 8.2-not estimable), and 17.5 months (95% CI, 10.7-21.1), respectively; ORRs were 47%, 33%, and 44%, respectively.

Similar improvements were noted in the wild-type group, which had a combination therapy ORR of 51%.

“Clinical trials investigating targeted therapies for KRAS-mutated NSCLC in the front line should include a chemo-immune checkpoint inhibitor comparator arm,” Dr Nakajima said.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Nakajima EC, Ren Y, Vallejo JJ, et al. Outcomes of first-line immune checkpoint inhibitors with or without chemotherapy according to KRAS mutational status and PD-L1 expression in patients with advanced NSCLC: FDA pooled analysis. Presented at ASCO 2022; June 3-7, 2022. Abstract 9001.