Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation
Another KRAS G12C inhibitor. Congrats to FCS Director of Drug Development Manish Patel, MD, one of the authors. Durable responses with less adverse events.
Updated Overall Survival and Exploratory Analysis From Randomized, Phase II EVAN Study of Erlotinib Versus Vinorelbine Plus Cisplatin Adjuvant Therapy in Stage IIIA Epidermal Growth Factor Receptor+ Non–Small-Cell Lung Cancer
Author(s): Dongsheng Yue, MD1; Shidong Xu, MD2; Qun Wang, MD3; Xiaofei Li, MD4; Yi Shen, MD5; Heng Zhao, MD6; Chun Chen, MD7; Weimin Mao, MD8; Wei Liu, MD9; Junfeng Liu, MD10; Lanjun Zhang, MD11; Haitao Ma, MD12; Qiang Li, MD13; Yue Yang, MD14; Yongyu Liu, MD15; Haiquan Chen, MD16; Zhenfa Zhang, MD1; Bin Zhang, MD1; Changli Wang, MD1
Source: DOI: 10.1200/JCO.22.00428 Journal of Clinical Oncology 40, no. 34 (December 01, 2022) 3912-3917.
Dr. Maen Hussein's Thoughts
Another EGFR inhibitor beating chemotherapy in EGFR mutated NSCLC in the adjuvant setting.
The randomized, open-label, phase II EVAN study investigated the efficacy (disease-free survival [DFS] and 5-year overall survival [OS]) and safety of erlotinib versus vinorelbine/cisplatin as adjuvant chemotherapy after complete resection (R0) for stage III epidermal growth factor receptor (EGFR) mutation+ non–small-cell lung cancer. We describe the updated results at the 43-month follow-up. In EVAN, patients were randomly assigned (1:1) to erlotinib (n = 51) or vinorelbine/cisplatin (n = 51). The median follow-up was 54.8 and 63.9 months in the erlotinib and chemotherapy arms, respectively. With erlotinib, the respective 5-year DFS by Kaplan-Meier analysis was 48.2% (95% CI, 29.4 to 64.7) and 46.2% (95% CI, 27.6 to 62.9) in the intention-to-treat and per-protocol populations. The median OS was 84.2 months with erlotinib versus 61.1 months with chemotherapy (hazard ratio, 0.318; 95% CI, 0.151 to 0.670). The 5-year survival rates were 84.8% and 51.1% with erlotinib and chemotherapy, respectively. In whole-exome sequencing analysis, frequent genes with variants co-occurring at baseline were TP53, MUC16, FAM104B, KMT5A, and DNAH9. With erlotinib, a single-nucleotide polymorphism mutation in UBXN11 was associated with significantly worse DFS (P = .01). To our knowledge, this study is the first to demonstrate clinically meaningful OS improvement with adjuvant erlotinib compared with chemotherapy in R0 stage III EGFR+ non–small-cell lung cancer.
Author Affiliations
1Tianjin Medical University Cancer Institute and Hospital, Tianjin, China 2Harbin Medical University Cancer Hospital, Harbin, China 3Zhongshan Hospital, Fudan University, Shanghai, China 4Tangdu Hospital, Fourth Military Medical University, Xi’an, China 5The Affiliated Hospital of Qingdao University, Qingdao, China 6Shanghai Jiao Tong University Affiliated Chest Hospital, Shanghai, China 7Fujian Medical University Union Hospital, Fuzhou, China 8Zhejiang Cancer Hospital, Hangzhou, China 9Jilin University First Hospital, Changchun, China 10Hebei Cancer Institute, Shijiazhuang, China 11Sun Yat-sen University Cancer Center, Guangzhou, China 12First Affiliated Hospital of Soochow University, Suzhou, China 13Sichuan Cancer Hospital and Institute, Chengdu, China 14Peking University Cancer Hospital, Beijing, China 15Liaoning Cancer Institute and Hospital, Shenyang, China 16Fudan University, Shanghai Cancer Center, Shanghai, ChinaRelated Articles
Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer
Neoadjuvant chemotherapy trial with post op nivolumab for 6 months shows promising results.
First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study
Patients with poor performance status do better on atezolizumab monotherapy vs. single agent chemotherapy.
Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer
Targeted therapy in NSCLC, FCS was part of this trial.
Perioperative Nivolumab and Chemotherapy in Stage III Non–Small-Cell Lung Cancer
The NADIM-II study looked at perioperative Nivo+chemo vs. chemo alone in stIIIA – stIIIB NSCLC. High pCR rates with chemoIO are again seen, as in the Checkmate 816 and NADIM-I study, they were even higher in this cohort (37%), suggesting higher-stage patients derive the biggest benefit from neoadjuvant chemoIO. Pretty impressive results, however, I still must point out that this was a phase II study with a small sample size, OS benefits have not been demonstrated and this has yet to make it on to NCCN.
