A phase 2 study of adjuvant carboplatin plus S-1 followed by maintenance S-1 therapy for patients with completely resected stage II/IIIA non-small cell lung cancer-Japanese Northern East Area Thoracic Surgery Study Group JNETS1302 study

Takeo Hasegawa; Hiroyuki Suzuki; Jiro Abe; Akira Sakurada; Chiaki Endo; Nobuyuki Sato; Tohru Hasumi; Hiroyuki Deguchi; Hiroyuki Oura; Satomi Takahashi; Hajime Saito; Hidetaka Uramoto; Motoyasu Sagawa; Yoshinori Okada

doi:10.21037/jtd-20-715

A phase 2 study of adjuvant carboplatin plus S-1 followed by maintenance S-1 therapy for patients with completely resected stage II/IIIA non-small cell lung cancer-Japanese Northern East Area Thoracic Surgery Study Group JNETS1302 study

J Thorac Dis. 2020 Jul;12(7):3591-3601. doi: 10.21037/jtd-20-715.

Authors

Takeo Hasegawa^{1

2}, Hiroyuki Suzuki^{1

2}, Jiro Abe^{1

3}, Akira Sakurada^{1

4}, Chiaki Endo^{1

4}, Nobuyuki Sato^{1

5}, Tohru Hasumi^{1

6}, Hiroyuki Deguchi^{1

7}, Hiroyuki Oura^{1

8}, Satomi Takahashi^{1

3}, Hajime Saito^{1

7}, Hidetaka Uramoto^{1

9}, Motoyasu Sagawa^{1

10}, Yoshinori Okada^{1

4}

Affiliations

¹ Japanese Northern East Area Thoracic Surgery Study Group, Seiryomachi, Sendai Aoba-ku, Japan.
² Department of Chest Surgery, Fukushima Medical University, Hikarigaoka, Fukushima, Japan.
³ Division of Thoracic Surgery, Miyagi Prefectural Cancer Center, Medeshimashiote Nodayama, Natori, Japan.
⁴ Department of Thoracic Surgery, Tohoku University, Seiryomachi, Sendai Aoba-ku, Japan.
⁵ Division of Thoracic Surgery, Aomori Prefectural Central Hospital, Higashitsukurimichi, Aomori, Japan.
⁶ Division of Thoracic Surgery, Sendai Medical Center, Miyagino, Sendai Miyagino-ku, Japan.
⁷ Department of Thoracic Surgery, Iwate Medical University, Uchimaru, Morioka, Japan.
⁸ Division of Thoracic Surgery, Iwate Prefectural Central Hospital, Ueda, Morioka, Japan.
⁹ Department of Thoracic Surgery, Kanazawa Medical University, Daigaku, Kahokugun Uchinadamachi, Japan.
¹⁰ Division of Endoscopy, Tohoku Medical and Pharmaceutical University, Komatsushima, Sendai Aoba-ku, Japan.

Abstract

Background: The standard adjuvant chemotherapy regimen for completely resected pathological stage II/IIIA non-small cell lung cancer (NSCLC) is four courses of cisplatin plus vinorelbine. However, the continuity and toxicity of cisplatin-based regimens remain problematic. Conversely, carboplatin-based chemotherapy is a less toxic and more tolerable regimen for various stages of NSCLC. In particular, the efficacy and tolerability of carboplatin plus S-1 in advanced NSCLC were confirmed by previous pivotal studies such as the LETS trail. Therefore, this phase II study assessed the feasibility, safety, and usefulness of carboplatin plus S-1 followed by maintenance S-1 as an adjuvant treatment.

Methods: In this single-arm, multicenter phase II study, 40 patients who previously underwent complete resection of NSCLC were enrolled from November 2013 to January 2015. The chemotherapy protocol was four cycles of carboplatin (AUC 5 on day 1) and oral S-1 (80 mg/m² every other day from days 1 to 21) followed by oral S-1 (80 mg/m² every other day for 48 weeks). The primary endpoint was the treatment completion rate, and the secondary endpoints were adverse events and 2-year recurrence-free survival.

Results: The treatment completion rate of the planned schedule was as low as 30.0% (90% confidence interval: 40.3-63.0%). The reasons for adjuvant chemotherapy discontinuation were adverse events, refusal, tumor recurrence, and other reasons in 13, 6, 10, and 2 patients, respectively. The 2-year progression-free survival rate was 66.7% among patients who completed maintenance chemotherapy. There were no treatment-related deaths, and most adverse events were less than grade 3.

Conclusions: Carboplatin plus S-1 followed by S-1 maintenance for 1 year in the adjuvant treatment of NSCLC was not tolerable, although most adverse events were not severe. However, patients who can fully complete the regimen might experience clinical benefit.

Keywords: Non-small cell lung cancer (NSCLC); S-1; adjuvant chemotherapy; carboplatin.