{"doi":"10.1093/oncolo/oyad197","title":"Outcomes of Combination Platinum-Doublet Chemotherapy and Anti-PD(L)-1 Blockade in KRASG12C-Mutant Non-Small Cell Lung Cancer","abstract":"BACKGROUND: Direct KRASG12C inhibitors are approved for patients with non-small cell lung cancers (NSCLC) in the second-line setting. The standard-of-care for initial treatment remains immune checkpoint inhibitors, commonly in combination with platinum-doublet chemotherapy (chemo-immunotherapy). Outcomes to chemo-immunotherapy in this subgroup have not been well described. Our goal was to define the clinical outcomes to chemo-immunotherapy in patients with NSCLC with KRASG12C mutations. PATIENTS AND METHODS: Through next-generation sequencing, we identified patients with advanced NSCLC with KRAS mutations treated with chemo-immunotherapy at 2 institutions. The primary objective was to determine outcomes and determinants of response to first-line chemo-immunotherapy among patients with KRASG12C by evaluating objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). We assessed the impact of coalterations in STK11/KEAP1 on outcomes. As an exploratory objective, we compared the outcomes to chemo-immunotherapy in KRASG12C versus non-G12C groups. RESULTS: One hundred and thirty eight patients with KRASG12C treated with first-line chemo-immunotherapy were included. ORR was 41% (95% confidence interval (CI), 32-41), median PFS was 6.8 months (95%CI, 5.5-10), and median OS was 15 months (95%CI, 11-28). In a multivariable model for PFS, older age (P = .042), squamous cell histology (P = .008), poor ECOG performance status (PS) (P < .001), and comutations in KEAP1 and STK11 (KEAP1MUT/STK11MUT) (P = .015) were associated with worse PFS. In a multivariable model for OS, poor ECOG PS (P = .004) and KEAP1MUT/STK11MUT (P = .009) were associated with worse OS. Patients with KRASG12C (N = 138) experienced similar outcomes to chemo-immunotherapy compared to patients with non-KRASG12C (N = 185) for both PFS (P = .2) and OS (P = .053). CONCLUSIONS: We define the outcomes to first-line chemo-immunotherapy in patients with KRASG12C, which provides a real-world benchmark for clinical trial design involving patients with KRASG12C mutations. Outcomes are poor in patients with specific molecular coalterations, highlighting the need to develop more effective frontline therapies.","journal":"The Oncologist","year":2023,"id":346550,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":243063,"name":"Biagio Ricciuti","orcid":"0000-0002-0651-2678","position":1,"is_corresponding":false},{"id":345563,"name":"Joao V. Alessi","orcid":"0000-0002-8072-5946","position":2,"is_corresponding":false},{"id":457319,"name":"Teng Fei","orcid":"0000-0001-7888-1715","position":3,"is_corresponding":false},{"id":917346,"name":"Hannah L. Kalvin","orcid":"0000-0002-6636-0602","position":4,"is_corresponding":false},{"id":237138,"name":"Jacklynn V. Egger","orcid":"0000-0002-2180-4169","position":5,"is_corresponding":false},{"id":91573,"name":"Hira Rizvi","orcid":"0000-0002-8007-096X","position":6,"is_corresponding":false},{"id":1024602,"name":"Rohit Thummalapalli","orcid":"0000-0002-8865-0299","position":7,"is_corresponding":false},{"id":243065,"name":"Giuseppe Lamberti","orcid":"0000-0003-3069-7630","position":8,"is_corresponding":false},{"id":269964,"name":"Andrew J. Plodkowski","orcid":"0000-0002-3772-370X","position":9,"is_corresponding":false},{"id":90691,"name":"Matthew D. Hellmann","orcid":"0000-0002-2670-9777","position":10,"is_corresponding":false},{"id":1281,"name":"Mark G. Kris","orcid":"0000-0002-7317-5341","position":11,"is_corresponding":false},{"id":15539,"name":"Maria E. Arcila","orcid":"0000-0001-5824-6554","position":12,"is_corresponding":false},{"id":616303,"name":"Marina K. Baine","orcid":"0000-0003-4939-6491","position":13,"is_corresponding":false},{"id":1555,"name":"Charles M. Rudin","orcid":"0000-0001-5204-3465","position":14,"is_corresponding":false},{"id":225996,"name":"Piro Lito","orcid":"0000-0003-2196-3503","position":15,"is_corresponding":false},{"id":1869,"name":"Marc Ladanyi","orcid":"0000-0001-9055-7213","position":16,"is_corresponding":false},{"id":39875,"name":"Adam J. Schoenfeld","orcid":"0000-0002-2644-1416","position":17,"is_corresponding":false},{"id":39879,"name":"Gregory J. Riely","orcid":"0000-0001-5357-4313","position":18,"is_corresponding":false},{"id":227614,"name":"Mark M. Awad","orcid":"0000-0003-0928-5244","position":19,"is_corresponding":false},{"id":237142,"name":"Kathryn C. Arbour","orcid":"0000-0001-5951-8427","position":20,"is_corresponding":false},{"id":105148,"name":"Arielle Elkrief","orcid":"0000-0003-1981-1535","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T01:11:53.085356Z","pmid":"37589215","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}