1403P - Sotorasib in KRAS p.G12C mutated advanced NSCLC: Real-word data from the Italian Expanded Access Program

Background

Sotorasib showed a significant improvement of progression free survival (PFS), safety and quality of life over docetaxel in patients with KRAS p.G12C–mutated advanced non–small-cell lung cancer (NSCLC) in the CodeBreak-200 study. Here we report real-world efficacy and tolerability data from NSCLC patients who received sotorasib within the Italian expanded access program (EAP).

Methods

Sotorasib (960 mg, orally, once daily) was available on physician request for KRAS p.G12C mutant advanced NSCLC patients who were pretreated with standard regimens or unfit for approved therapies. Clinical-pathological and molecular data were collected from the Italian ATLAS real-word registry. Patients underwent CT-scan and responses were evaluated by RECIST criteria. Efficacy and tolerability outcomes have been assessed.

Results

A total of 190 advanced NSCLC patients were treated across 30 Italian centres. The overall patients’ median age was 68 years old (range 32-85). Most patients were male (62%), former (49%) or current smokers (42%), with ECOG performance status 0/1 (84%) and adenocarcinoma subtype (89%). Tumor PD-L1 expression was ≥ 50%, 1-49% and <1% in 25%, 37% and 31% of patients, respectively. Patients had received a median of 2 (0–4) previous lines of systemic therapy, with 44% and 33% of them receiving sotorasib in 2^nd and 3^rd line, respectively. Overall, response rate was 26% and disease control rate 66%. Median PFS was 6.1 months (95% CI: 5.6 – 9.1). Median overall survival (OS) was 8.2 months (95% CI: 6.7-13.6) without significant differences across the main clinical subgroups [age (< 70 vs ≥ 70 years, p= 0.83), treatment line (1^st/2^nd vs >2^nd, p=0.3), brain metastases (p=0.53)]. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 32 patients (17%), with no significant differences between who received or not previous immunotherapy (16% vs 14%, respectively). The most common TRAEs were hepatotoxicity (12%), diarrhea (3%) and asthenia (1%).

Conclusions

Real-world data from the Italian EAP confirm the activity and tolerability of sotorasib in pre-treated patients with KRAS p.G12C-mutated advanced NSCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

F. Passiglia: Financial Interests, Advisory Board: AstraZeneca, Janssen, Amgen, Sanofi, Roche, MSD, BMS, BeiGene, Thermo Fisher Scientific. G. Minuti: Financial Interests, Advisory Board: Roche, BMS, AstraZeneca, Gilead, Novartis, Sanofi. E. Bria: Financial Interests, Advisory Board: MSD Oncology, AstraZeneca, Pfizer, Lilly, Bristol Myers Squibb, Roche. S. Pilotto: Financial Interests, Advisory Board: AstraZeneca, Eli Lilly & Co, Boehringer Ingelheim, Merck Sharp and Dohme, Roche, Bristol-Myers Squibb. C. Genova: Financial Interests, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Merck-Sharp-Dohme, Roche, Takeda. R. Chiari: Financial Interests, Advisory Board: Takeda. S. Novello: Financial Interests, Advisory Board: Boehringer Ingelheim, AstraZeneca, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Eli Lilly. All other authors have declared no conflicts of interest.