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David S. Ettinger, MD, FACP, FCCP

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Pooled Analysis of Appropriate NSCLC Populations for First-Line Immunotherapy Plus Chemotherapy

By: Celeste L. Dixon
Posted: Tuesday, July 5, 2022

Patients with KRAS-mutated non–small cell lung cancer (NSCLC) may well benefit from first-line combination chemotherapy with immune checkpoint inhibition, just as those with KRAS wild-type NSCLC do. The results of a retrospective pooled analysis of 12 registrational clinical trials suggest that upfront combination therapy—versus immune checkpoint inhibitor therapy alone or chemotherapy alone—may be effective for these patients. However, the data indicate that immune checkpoint inhibition is not advised for patients with NSCLC who have any other targetable mutations. Erica C. Nakajima, MD, of the U.S. Food and Drug Administration’s Center for Drug Evaluation and Research, and colleagues presented these data at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9001).

The 12 trials investigated the efficacy of first-line immune checkpoint inhibitor therapy, with or without chemotherapy, and of chemotherapy alone in patients with documented KRAS status (mutant, wild-type, and G12C). Of the approximately 9,000 patients pooled, KRAS mutational status was reported in 1,430 (61% wild-type, 39% mutated), and KRAS G12C was found in 11% of those with a KRAS mutation. The G12C subgroup’s small size limited the interpretation of those data, according to the authors. Demographics of all groups were similar (60% male; 89% White; 67% former or current smokers).

Median overall survival was 22.4 months in patients with KRAS mutations who were treated with immune checkpoint inhibitor therapy plus chemotherapy compared with 18.7 months in those with wild-type KRAS. Moreover, all patients, regardless of PD-L1 status, appeared to benefit from this combination approach, reported the investigators.

However, “a more refined assessment of the response to immune checkpoint inhibitors according to specific KRAS mutations is needed,” said Dr. Nakajima in the ASCO Daily News. “Some evidence shows that patients with NSCLC harboring other KRAS mutations, such as KRAS G12D, may be less responsive to [immune checkpoint inhibition] compared with patients with non–KRAS G12D disease.”

Disclosure: The study authors’ disclosure information can be found at coi.asco.org.


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