Randomized phase III study of pemetrexed plus cisplatin versus vinorelbine plus cisplatin for completely resected stage II to IIIA nonsquamous non–small-cell lung cancer

Hirotsugu Kenmotsu, Nobuyuki Yamamoto, Takeharu Yamanaka, Katsuo Yoshiya, Toshiaki Takahashi, Tsuyoshi Ueno, Koichi Goto, Haruko Daga, Norihiko Ikeda, Kenji Sugio, Takashi Seto, Shinichi Toyooka, Hiroshi Date, Tetsuya Mitsudomi, Isamu Okamoto, Kohei Yokoi, Hideo Saka, Hiroaki Okamoto, Yuichi Takiguchi, Masahiro Tsuboi

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Abstract

PURPOSE To evaluate the efficacy of pemetrexed plus cisplatin versus vinorelbine plus cisplatin as postoperative adjuvant chemotherapy in patients with pathologic stage II-IIIA nonsquamous non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS We performed a randomized, open-label, phase III study at 50 institutions within 7 clinical study groups in Japan. Patients with completely resected pathologic stage II-IIIA (TNM 7th edition) nonsquamous NSCLC were randomly assigned to receive either pemetrexed (500 mg/m2, day 1) plus cisplatin (75 mg/m2, day 1) or vinorelbine (25 mg/m2, days 1 and 8) plus cisplatin (80 mg/m2, day 1) with stratification by sex, age, pathologic stage, EGFR mutation, and institution. These treatments were planned to be given every 3 weeks for 4 cycles. The primary end point was recurrence-free survival in the modified intent-to-treat population, excluding ineligible patients. RESULT Between March 2012 and August 2016, 804 patients were enrolled (402 assigned to vinorelbine plus cisplatin and 402 assigned to pemetrexed plus cisplatin). Of 784 eligible patients, 410 (52%) had stage IIIA disease and 192 (24%) had EGFR-sensitive mutations. At a median follow-up of 45.2 months, median recurrence-free survival was 37.3 months for vinorelbine plus cisplatin and 38.9 months for pemetrexed plus cisplatin, with a hazard ratio of 0.98 (95% CI, 0.81 to 1.20; 1-sided P 5 .474). Grade 3-4 toxicities reported more frequently for vinorelbine plus cisplatin than for pemetrexed plus cisplatin were febrile neutropenia (11.6% v 0.3%, respectively), neutropenia (81.1% v 22.7%, respectively), and anemia (9.3% v 2.8%, respectively). One treatment-related death occurred in each arm. CONCLUSION Although this study failed to show the superiority of pemetrexed plus cisplatin for patients with resected nonsquamous NSCLC, this regimen showed a better tolerability as adjuvant chemotherapy.

Original languageEnglish
Pages (from-to)2187-2196
Number of pages10
JournalJournal of Clinical Oncology
Volume38
Issue number19
DOIs
Publication statusPublished - May 14 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Kenmotsu, H., Yamamoto, N., Yamanaka, T., Yoshiya, K., Takahashi, T., Ueno, T., Goto, K., Daga, H., Ikeda, N., Sugio, K., Seto, T., Toyooka, S., Date, H., Mitsudomi, T., Okamoto, I., Yokoi, K., Saka, H., Okamoto, H., Takiguchi, Y., & Tsuboi, M. (2020). Randomized phase III study of pemetrexed plus cisplatin versus vinorelbine plus cisplatin for completely resected stage II to IIIA nonsquamous non–small-cell lung cancer. Journal of Clinical Oncology, 38(19), 2187-2196. https://doi.org/10.1200/JCO.19.02674