Patients with KRAS G12C–Mutated NSCLC Experience a Short PFS When Treated with Docetaxel-Containing Regimens

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On May 28, 2021, the US Food and Drug Administration granted accelerated approval for the use of sotorasib as a second-line or later treatment in patients with locally advanced or metastatic non–small-cell lung cancer (NSCLC) harboring the KRAS G12C mutation. This was an important approval as prior to this there were no approved therapies for KRAS-mutated NSCLC. Approval was based on a study that showed an objective response rate of 37.1%, an 11.1-month median duration of response, and a median progression-free survival (PFS) of 6.8 months in patients primarily treated in the third line or later.

To determine the clinical outcomes of 396 patients with NSCLC harboring the KRAS G12C mutation in the second line or later, a multicenter, retrospective chart review of the clinical outcomes of these patients was performed. KRAS G12C mutation was found in 110 patients at diagnosis and in 286 patients later in their disease process. There were 235 women in the study, and 73% of the patients were White. Current or former smokers comprised 94% of the study population, and the median age at metastatic NSCLC diagnosis was 67 years.

Among the patients, 68% had stage IV NSCLC, 14% had stage III NSCLC, 8% had stage II NSCLC, and 7% had stage I NSCLC. PD-L1 score was known for 211 patients: 27% had <1% expression, 23% had 1% to 49% expression, and 49% had ≥50% expression. Brain metastases developed in 9% of patients, and liver metastases were found in 7% of the patients during the course of their disease.

In the 201 patients with KRAS G12C confirmed prior to first-line therapy, the median first-line real-world PFS (rwPFS) was 9.3 months and the median overall survival was 16.8 months. First-line therapy was platinum-doublet chemotherapy monotherapy in 44% of these patients, 30% had PD-(L)1 inhibitor monotherapy, and 18% had platinum chemotherapy plus PD-(L)1 inhibitor combination therapy. Second-line therapy was documented in 123 patients: PD-(L)1 inhibitor monotherapy was given to 31% of patients, 15% received platinum-based chemotherapy alone, 9% had platinum-based chemotherapy plus a PD-(L)1 inhibitor, and 45% of patients were treated with other regimens. Among these patients, the median rwPFS was 8.3 months; the median rwPFS was 4.6 months among 10 patients who were treated with docetaxel, with 1 of these patients also receiving ramucirumab. A co-occurring STK11 mutation was found in 12% of patients. For these patients, the median rwPFS on first-line therapy was 6.0 months.

Source: Iams WT, Balbach ML, Phillips S, et al. A multicenter retrospective chart review of clinical outcomes among patients with KRAS G12C mutant non–small cell lung cancer. Clin Lung Cancer. 2023 Feb 8. Epub ahead of print.

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