Abstract 97P
Background
In the absence of head-to-head trials, a MAIC was conducted to evaluate efficacy and safety of sotorasib and adagrasib, the only approved KRAS G12C inhibitors for NSCLC in the United States and Europe.
Methods
MAIC compared data from phase III trials: CodeBreaK (CB) 200 (patient-level data for sotorasib) and KRYSTAL-12 (aggregate data for adagrasib). An unanchored (base-case) MAIC was preferred over anchored (sensitivity analysis), due to differential bias in comparator arm (early dropout, cross-over, protocol deviations). The MAIC adjusted for prognostic factors and effectmodifiers such as age, sex, region, prior treatment, brain metastases and liver metastases. Sensitivity analyses adjusted for additional covariates and utilized an anchored approach. Hazard ratios (HR) for progression-free survival (PFS), odds ratio (OR) for objective response rate (ORR) and safety outcomes were estimated. PFS was also evaluated in the subgroup of patients with baseline brain metastases.
Results
In the base-case, an effective sample size of 70.7% was achieved from CB 200. In the overall population, sotorasib and adagrasib showed comparable efficacy for PFS (HR: 0.93, P=0.6 and ORR (OR: 0.86, P=0.5), with no significant differences. However, in patients with brain metastases, sotorasib was associated with a 39% lower risk of systemic progression than adagrasib (HR: 0.61, P=0.04). Regarding safety, sotorasib showed better outcomes (OR, P) for any grade treatment-related adverse events (TRAEs) (0.20,
Conclusions
Sotorasib demonstrated comparable efficacy vs adagrasib in patients with advanced NSCLC, with the PFS point estimate favoring sotorasib in patients with brain metastases. Sotorasib also exhibited a favorable safety profile compared to adagrasib.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
J. Wolf: Financial Interests, Institutional, Advisory Board: AbbVie, Amgen, AstraZeneca, Beigene, Blueprint, BMS, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Ellipses Pharma, Genmab, Janssen, Lilly, Loxo, Merck, Mirati, MSD, Novartis, Nuvalent, Pfizer, Pierre-Fabre, Regeneron, Roche, Seattle Genetic; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Janssen Pharmaceutica, Novartis, Pfizer. D. Chopra: Financial Interests, Institutional, Stocks/Shares: Amgen; Other, Institutional, Full or part-time Employment: Amgen. Z. Lan: Financial Interests, Institutional, Other, Consulting Fees: Amgen; Financial Interests, Institutional, Full or part-time Employment: Cytel. D.M. Waterhouse: Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, AZTherapies, AbbVie, Amgen, McGivenny Global, Janssen Oncology, Seattle Genetics, Exelixis, Eisai, EMD Serono, Merck, Pfizer, Mirati Therapeutics, Regeneron, Sanofi, Lilly, Astellas, Gilead, Takeda, Daiichi, Novartis, Bayer, Aveo; Financial Interests, Institutional, Speaker’s Bureau: Bristol Myers Squibb, Janssen Oncology, Merck, AstraZeneca, Amgen, EMD Serono,; Financial Interests, Institutional, Other, Travel and Accommodations: Bristol Myers Squibb. E. Felip: Financial Interests, Institutional, Advisory Role: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi, F. Hoffmann – La Roche, Gilead, GSK, Iteos Therapeutics, Janssen, Johnson & Johnson, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Regeneron, TUR; Financial Interests, Institutional, Invited Speaker, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Gilead, Janssen, Johnson & Johnson, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Peervoice, Pfizer, Regeneron; Financial Interests, Institutional, Other, Support for meetings/travel: AstraZeneca, Janssen, Roche; Financial Interests, Institutional, Member, Independent Member of the board: Grifols. H. Moradian: Financial Interests, Institutional, Other, Consulting Fees: Amgen; Other, Institutional, Full or part-time Employment: Cytel. N. Karim: Financial Interests, Institutional, Stocks/Shares: Amgen; Other, Institutional, Full or part-time Employment: Amgen. C. Obiozor: Financial Interests, Institutional, Full or part-time Employment: Amgen. B. Stollenwerk: Financial Interests, Institutional, Stocks/Shares: Amgen; Other, Institutional, Full or part-time Employment: Amgen.