ICIs Found to Have Benefit in NSCLC with KRAS Mutations

Lung cancer remains the leading cause of cancer worldwide, with non–small-cell lung cancer (NSCLC) representing 85% of all lung cancer cases. Kirsten rat sarcoma viral oncogene (KRAS) mutation occurs in 25% of Western-population NSCLC cases, with a much lower 5% to 15% occurrence in Asian populations. Historically, standard treatment for KRAS-mutated NSCLC has been chemotherapy, but the development of KRAS inhibitors and immune checkpoint inhibitors (ICIs) has made precision medicine available, and in the past 5 years ICIs have become standard treatment for patients with metastatic NSCLC. Despite these advances in treatment, the efficacy of ICIs is controversial as there are limited efficacy data in patients with NSCLC harboring KRAS mutations.

To better understand the efficacy of ICIs in patients with advanced NSCLC with KRAS mutations, a retrospective analysis evaluating efficacy and prognosis in patients treated with ICIs in the real world was performed. In addition, the differences in ICI efficacy were also studied among KRAS-mutated subtypes.

The study included 95 patients who were grouped according to number of lines of treatment and treatment regimen. Former or current smokers made up 69.5% of the study population, and 95.8% of tumors were adenocarcinoma. Intrathoracic metastases were found in 52 patients, 33 patients had bone metastasis, 21 had brain metastasis, and 6 had liver metastasis. Mutation types were as follows: 24.2% had KRAS G12C, 44.2% had KRAS non-G12C, and 31.6% had unknown mutations.

First-line treatment consisted of ICIs plus platinum chemotherapy or platinum chemotherapy alone. Second-line treatment was ICI monotherapy or chemotherapy alone. ICIs were given as first- and second-line therapy for 61.1% of patients, with 33 patients also receiving platinum-based chemotherapy as first-line therapy. Platinum-based chemotherapy monotherapy was received by 37 patients as first-line therapy. When second-line therapy was evaluated, 25 patients received ICI monotherapy and 10 who were treated with platinum-based chemotherapy as first-line treatment received chemotherapy monotherapy.

First-line ICIs plus platinum-based chemotherapy treatment gave patients a progression-free survival (PFS) of 7.4 months and overall survival (OS) of 24.1 months versus 4.5 months and 13.2 months, respectively, in patients who received platinum-based chemotherapy monotherapy. When second-line therapy was evaluated, ICI monotherapy gave patients a PFS of 4.8 months and OS of 18.0 months versus a PFS of 3.0 months and OS of 13.8 months for patients receiving chemotherapy monotherapy. Subtype evaluation found that patients with NSCLC harboring KRAS mutation and those with NSCLC harboring KRAS wild-type mutation treated with ICIs had no significant difference in PFS and OS. In KRAS G12C and KRAS non-G12C patients, no significant difference was seen in PFS and OS with ICI use.

Source: Gu X, Si J, Guan Y, et al. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: a retrospective analysis. Open Med (Wars). 2023;18(1):20230653.