ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
This article is part of the Research TopicReal-World Data and Real-World Evidence in Lung Cancer Volume IIView all 15 articles
Impact of KRAS G12C mutation on the efficacy of chemoradiotherapy in patients with unresectable stage II or III non-small cell lung cancer
Provisionally accepted
Jean CABON1*
Delphine Lerouge1
THUREAU Sébastien2Jacques Balosso1Marin Guigo1Radj Gervais1Catherine Dubos1Pascal Dô1Pierre Demontrond1Hubert Curcio1Simon Deshayes3Jeannick Madelaine3
Dimitri Leite Ferreira3Leonard Jacson3Kilian Lecrosnier4
François Chevalier4Florian Guisier5Edouard Dantoing5Alexandra Leconte1François Christy1Mathieu Césaire1- 1Centre Francois Baclesse Centre de Lutte Contre le Cancer, Caen, France
- 2Centre Henri Becquerel, Rouen, France
- 3Centre Hospitalier Universitaire de Caen Normandie, Caen, France
- 4Grand Accelerateur National d'Ions Lourds, Caen, France
- 5Centre Hospitalier Universitaire de Rouen, Rouen, France
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Background: Approximately 35% of patients with non-small cell lung cancer (NSCLC) have locally advanced disease. Despite treatment with chemoradiotherapy (CRT) and consolidation immunotherapy, overall survival remains below 50% at 5 years. KRAS mutations (KRASm) are the most common lung cancer mutations, affecting 25% of NSCLC. KRASm can cause radioresistance and several targeted KRASm therapies have been developed, mainly targeting the KRAS G12C mutation (KRASm G12C), but the impact of KRASm G12C on the efficacy of CRT for locally advanced NSCLC remains unclear. Methods: We conducted a multicenter retrospective study of unresectable stage II or III NSCLC treated with CRT in four French hospitals between January 2014 and December 2022. The primary endpoint was the objective response rate (ORR) for KRASm G12C compared to KRAS wild-type (KRASwt). The main secondary objectives were to assess the difference in ORR between KRASm and KRASwt, the difference in disease control rate (DCR), overall survival (OS), progression-free survival (PFS), time to local relapse (TTLR), time to distant relapse (TTDR) according to KRASm status. Results: Our study included 267 patients and 73 patients had KRASm (27.3%). The most common KRASm was KRASm G12C (n=42). Tumors were lung adenocarcinoma for 91% (n=244) of patients. Two hundred (75%) patients were treated with concomitant CRT. There was no difference between KRASm G12C and KRASwt patients in terms of ORR (48% vs 49%; p=0.961) and DCR (86% vs 84%; p=0.903), neither when comparing KRASm to KRASwt in terms of OS (p=0.64), PFS (p=0.28), TTLR (p=0.26) and TTDR (p=0.3), with no impact after adjustment for durvalumab. Conclusion: KRAS G12C mutation compared to KRAS wild-type patients did not affect response to chemoradiotherapy, and KRAS mutations compared to KRAS wild-type were not
Keywords: Non-small cell lung cancer, KRAS mutant, KRAS G12C mutation, Chemoradiatherapy, Locally advance disease
Received: 29 Jul 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 CABON, Lerouge, Sébastien, Balosso, Guigo, Gervais, Dubos, Dô, Demontrond, Curcio, Deshayes, Madelaine, Ferreira, Jacson, Lecrosnier, Chevalier, Guisier, Dantoing, Leconte, Christy and Césaire. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jean CABON, jean.cabon10@gmail.com
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