Patients with Lung Cancer Harboring KRAS G12C Mutation and Higher PD-L1 Expression Benefit from Immunotherapy

Lung cancer survival has improved during the past decade, with more effective therapies driving this improvement.¹ Chemotherapy is the standard treatment, but targeted therapies have also entered into the standard of care.¹ KRAS mutations occur in 25% to 30% of patients with lung adenocarcinomas (LUADs), and KRAS G12C accounts for 40% of these mutations.¹ In the past, KRAS G12C had been considered undruggable, but it has recently become a targetable mutation.¹

To better understand if targeted treatment is preferrable to immunotherapy in patients with LUADs, a study was performed to assess clinical and pathological characteristics and outcomes of immunotherapy in patients with LUADs. KRAS G12C–harboring tumors were compared with tumors without targetable alterations, other KRAS mutations, and other targetable alterations. The study included 89 patients with LUADs who were treated with immunotherapy between January 2017 and July 2020. Patient median age was 64 years, and 78.6% of patients were men. Current smokers comprised 55% of the study population, and 38.2% of patients were former smokers. Stage IV cancer was found in 75.2% of patients, stage III in 14.6%, stage II in 7.9%, and stage I in 2.2%.

Molecular analysis found that 53 patients had no targetable alterations. MET amplification or exon skipping was found in 5 patients, BRAF mutation occurred in 3 patients, and RET rearrangement, EGFR mutation, NTRK rearrangement, and HER2 mutation occurred in 1 patient each. KRAS mutations were found in 24 patients, and KRAS G12C was found in 58.3% of KRAS mutations, KRAS G12A in 16.6%, KRAS G12V in 16.6%, KRAS G12F in 4.2%, and KRAS G13C in 4.2%. When PD-L1 status was evaluated for KRAS G12C mutations, PD-L1 ≥50% was found in 7 patients, and PD-L1–negative tumor was found in 1 patient. In KRAS mutation other than KRAS G12C, PD-L1 ≥50% was found in 2 patients, and 6 patients were PD-L1–negative.

The overall response rate to immunotherapy was 31.25% for patients with KRAS G12C mutation. Other KRAS mutations had an 18.2% overall response to immunotherapy. The overall survival rate for patients with KRAS G12C LUAD was 16.32 months, whereas the overall survival rate for patients with other KRAS mutations was 9.7 months.

The researchers concluded that patients with LUAD who had the KRAS G12C mutation with higher PD-L1 expression appeared to benefit from immunotherapy compared with patients who had other KRAS mutations.

Reference

1. Arbour KC, Rizvi H, Plodkowski AJ, et al. Treatment outcomes and clinical characteristics of patients with KRAS-G12C-mutant non-small cell lung cancer. Clin Cancer Res. 2021;27(8):2209-2215.

Source: Pinto L, da Rocha S, Clave S, et al. KRAS G12C lung adenocarcinoma represents a distinct group of patients with different response to immunotherapy. Ann Oncol. 2022;33(suppl 2):S105-S110.