Real-world effectiveness and tolerability of sotorasib in patients with KRAS G12C-mutated metastatic non-small cell lung cancer: The IFCT-2102 Lung KG12Ci study.

INTRODUCTION

Sotorasib has shown efficacy in a phase 3 trial compared to docetaxel among previously treated non-small cell lung cancer (NSCLC) patients with a KRAS G12C mutation. However, its real-world effectiveness and tolerance, especially post-immunotherapy, remain debated.

METHODS

This French retrospective multicentre study analysed NSCLC patients receiving at least one dose of sotorasib as part of early access program The main objective was to assess real-world progression-free survival (rwPFS), and secondary objectives included assessment of overall survival (rwOS) and sotorasib-related hepatotoxicity.

RESULTS

458 patients from 76 centres were analysed, with a median age 65.8. Among them, 43.4 % were female, 28.3 % had performance status ≥ 2, 95.4 % were active/former smokers, and 38.0 % had brain metastases with 55.2 % in progression at sotorasib initiation. PD-L1 expression was < 1 %, ≥ 1-49 %, ≥ 50 %, and unknown in 35.1 %, 34.1 %, 23.4 %, and 7.4 % of patients, respectively. Most patients had received prior treatments (96.7 %), including immunotherapy (54.9 %). Median (95 % confidence interval [CI]) rwPFS and rwOS were 3.5 (3.1-4.2) and 8.3 (7.5-9.3) months, with a median (95 % CI) follow-up of 15.8 (13.9-17.3) and 16.4 (15.5-17.3) months, respectively. The real-world objective response rate (rwORR) was 33.2 % and disease control rate (rwDCR) was 63.2 %. In patients with brain metastases, cerebral rwORR and rwDCR were 20.1 % and 66.9 %, respectively. Grade 3-4 adverse events related to hepatotoxicity occurred in 5.2 % of patients. Sotorasib was discontinued for toxicity in 16.5 % of patients.

CONCLUSION

This study gave insights into effectiveness and safety of sotorasib in a real-world setting, in advanced or metastatic KRAS G12C-mutated non-squamous NSCLC.