PIT-2: A multicenter phase II trail of S-1 plus cisplatin with concurrent radiotherapy followed by surgery in stage IIIA (N2) lung squamous cell carcinoma.

Abstract

8543 Background: A multicenter phase II study, PIT-2 (Personized Induction Therapy-2), was performed to investigate the efficacy and safety of S-1 plus cisplatin and concurrent thoracic radiation therapy (TRT) followed by surgery in patients with stage IIIA (N2) lung squamous cell carcinoma (LSCC). To date, no clinical trials on the use of induction therapy prior to surgery have focused solely on the treatment of N2 LSCC. Methods: Eligible patients were 20 to 75 years old and had stage IIIA (pathologically proven N2) LSCC, performance status of 0-1, and no prior treatment. The patients received induction therapy consisting of three cycles of S-1 and cisplatin plus concurrent TRT (45 Gy in 25 fractions) followed by surgery. S-1 was administered orally at 40 mg/m2 twice per day, on days 1 through 14 along with an intravenous infusion of cisplatin (60 mg/m2) on day 1. The treatment cycles were repeated every four weeks. The primary endpoint was 2-year progression-free survival (PFS) rate and key secondary endpoints included overall survival (OS), the objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumors version 1.1, pathological complete remission (pCR) rate, feasibility, and toxicity. Results: Of the 45 patients registered between December 2013 and September 2018, 43 received induction therapy. Of the 43 patients, 39 (91%) underwent surgery (25 lobectomies, 10 bilobectomies, three pneumonectomies, and one wedge resection). The complete resection rate was 95% (37/39). Median follow-up time was 35.7 months. The 2-year PFS and OS rates were 67% (90% CI: 54-78%) and 70% (95% CI: 53-81%), respectively. The ORR and pCR rates were 86% (37/43, 95% CI: 76-96%) and 39% (15/39, 95% CI: 23-54%), respectively. Grade (G) 3 or 4 toxicities during the induction therapy in 43 patients included neutropenia (40%), anemia (9%), thrombocytopenia (7%), and hyponatremia (7%). Severe surgical complications in 39 patients included G3/4 pneumonia (5%), G3 bronchopleural fistula (5%), and G3 pleural effusion (5%). No G3/4 intraoperative adverse events occurred. There was no 30-day postoperative mortality and one 90-day postoperative mortality in a patient who underwent right pneumonectomy and developed pneumonia after discharge. Conclusions: Induction therapy using S-1 plus cisplatin and concurrent TRT followed by surgery is a promising treatment for patients with stage IIIA (N2) LSCC. Clinical trial information: 000012413.