Predictive value of EGFR mutation in non-small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy.

Abstract

The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non-small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P = .0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P = .0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P = .0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).

• Authors: Toshiaki Takahashi, Kazuko Sakai, Hirotsugu Kenmotsu, Kiyotaka Yoh, Haruko Daga, Tatsuo Ohira, Tsuyoshi Ueno, Tadashi Aoki, Hidetoshi Hayashi, Koji Yamazaki, Yukio Hosomi, Toyofumi F Chen-Yoshikawa, Norihito Okumura, Yuichi Takiguchi, Akimasa Sekine, Tomohiro Haruki, Hiromasa Yamamoto, Yuki Sato, Hiroaki Akamatsu, Takashi Seto, Sho Saeki, Kenji Sugio, Makoto Nishio, Hidetoshi Inokawa, Nobuyuki Yamamoto, Kazuto Nishio, Masahiro Tsuboi
• Journal: Cancer science (Cancer Sci) Vol. 113 Issue 1 Pg. 287-296 (Jan 2022) ISSN: 1349-7006 [Electronic] England
• PMID: 34689382 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial)
• Copyright: © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Pemetrexed
• EGFR protein, human
• ErbB Receptors
• Cisplatin
• Vinorelbine

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, genetics, surgery)
• Chemotherapy, Adjuvant
• Cisplatin (therapeutic use)
• ErbB Receptors (genetics)
• Female
• High-Throughput Nucleotide Sequencing
• Humans
• Lung Neoplasms (drug therapy, genetics, surgery)
• Male
• Mutation
• Pemetrexed (therapeutic use)
• Precision Medicine
• Prognosis
• Sequence Analysis, DNA
• Survival Analysis
• Treatment Outcome
• Vinorelbine (therapeutic use)