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David S. Ettinger, MD, FACP, FCCP

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SITC 2022: Outcomes of Combination Therapy for Advanced NSCLC Stratified by KRAS Status

By: Vanessa A. Carter, BS
Posted: Monday, November 28, 2022

During the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 1403), Jyoti Patel, MD, FASCO, of Robert H. Lurie Comprehensive Cancer Center, Chicago, and colleagues presented their real-world data analysis for outcomes following first-line immunotherapy with or without chemotherapy in patients with non–small cell lung cancer (NSCLC) harboring KRAS mutations. This is reportedly the largest data analysis among this patient population, and the results imply that these individuals may require a tailored trial design because of outcome variability.

“Our analysis suggests that advanced NSCLC patients with KRAS mutations, including G12C with high PD-L1, had the best outcomes when treated with first-line immune checkpoint inhibitors including [immunotherapy] alone,” the investigators concluded. “Outcomes were significantly worse when STK11/KEAP1 co-mutations were present.”

The Tempus Lens database was queried to respectively analyze 2,680 patients with advanced NSCLC who underwent first-line chemotherapy or immunotherapy with or without chemotherapy. Participants were stratified by KRAS mutational status: mutant, a G12C point mutation, or wild-type. Subgroup analyses were stratified by KRAS status; PD-L1 status; and pathogenic aberrations in KEAP1, TP53, and STK11.

Approximately 31.4% of patients presented with a KRAS mutation—11.3% of them being G12C point mutations. Additionally, those with a PD-L1 tumor proportion score of at least 50% had the highest incidence of KRAS mutations and G12C groups when compared with wild-type. Although demographics were well balanced, there was a higher frequency of squamous histology (25% vs. 4%) and never-smokers (14% vs. 5%) among those with mutant versus wild-type disease.

Of note, the prevalence of aberrations in TP53 (48% vs. 37%), STK11 (16% vs. 10%), and KEAP1 (9% vs. 8%) occurred more often in those with KRAS mutations than not. Regardless of KRAS mutational status, those receiving immune checkpoint inhibitors alone demonstrated the highest overall survival rates. The G12C and PD-L1 group demonstrated the longest median overall survival of 47.4 months.

Disclosure: Disclosure information was not provided.


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