KRAS(G12C) mutation is associated with increased risk of recurrence in surgically resected lung adenocarcinoma Journal Article
| Authors: | Jones, G. D.; Caso, R.; Tan, K. S.; Mastrogiacomo, B.; Sanchez-Vega, F.; Liu, Y.; Connolly, J. G.; Murciano-Goroff, Y. R.; Bott, M. J.; Adusumilli, P. S.; Molena, D.; Rocco, G.; Rusch, V. W.; Sihag, S.; Misale, S.; Yaeger, R.; Drilon, A.; Arbour, K. C.; Riely, G. J.; Rosen, N.; Lito, P.; Zhang, H.; Lyden, D. C.; Rudin, C. M.; Jones, D. R.; Li, B. T.; Isbell, J. M. |
| Article Title: | KRAS(G12C) mutation is associated with increased risk of recurrence in surgically resected lung adenocarcinoma |
| Abstract: | Purpose: KRASG12C is the most common KRAS mutation in primary lung adenocarcinoma. Phase I clinical trials have demonstrated encouraging clinical activity of KRASG12C inhibitors in the metastatic setting. We investigated disease-free survival (DFS) and tumor genomic features in patients with surgically resected KRASG12C-mutant lung adenocarcinoma. Experimental Design: Patients who underwent resection of stage I-III lung adenocarcinoma and next-generation sequencing (NGS) were evaluated. Exclusion criteria were receipt of induction therapy, incomplete resection, and low-quality NGS. Mutations were classified as KRAS wild-type (KRASwt), G12C (KRASG12C), or non-G12C (KRASother). DFS was compared between groups using the log-rank test; factors associated with DFS were assessed using Cox regression. Mutual exclusivity and cooccurrence, tumor clonality, and mutational signatures were assessed. Results: In total, 604 patients were included: 374 KRASwt (62%), 95 KRASG12C (16%), and 135 KRASother (22%). Three-year DFS was not different between KRAS-mutant and KRASwt tumors. However, 3-year DFS was worse in patients with KRASG12C than KRASother tumors (log-rank P = 0.029). KRASG12C tumors had more lymphovascular invasion (51% vs. 37%; P = 0.032) and higher tumor mutation burden [median (interquartile range), 7.0 (5.3-10.8) vs. 6.1 (3.5-9.7); P = 0.021], compared with KRASother tumors. KRASG12C mutation was independently associated with worse DFS on multivariable analysis. Our DFS findings were externally validated in an independent The Cancer Genome Atlas cohort. Conclusions: KRASG12C mutations are associated with worse DFS after complete resection of stage I-III lung adenocarcinoma. These tumors harbormore aggressive clinicopathologic and genomic features than other KRAS-mutant tumors. We identified a high-risk group for whom KRASG12C inhibitors may be investigated to improve survival. © 2021 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 27 |
| Issue: | 9 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2021-05-01 |
| Start Page: | 2604 |
| End Page: | 2612 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-20-4772 |
| PUBMED: | 33593884 |
| PROVIDER: | scopus |
| PMCID: | PMC8102372 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2021 -- Source: Scopus |
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