PIT-1: Randomized phase II trail of pemetrexed-cisplatin plus bevacizumab or concurrent thoracic radiation therapy followed by surgery in stage IIIA (N2) nonsquamous non-small cell lung cancer.

Abstract

9014 Background: PIT-1 (Personized Induction Therapy-1) is a multicenter, open-label, randomized phase II study using selection design of platinum doublet chemotherapy plus angiogenesis inhibitor or concurrent thoracic radiation therapy (TRT) as induction therapy followed by surgery in patients with stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC) to investigate the efficacy and safety of these treatment strategies. Methods: Patients with stage IIIA (pathologically proven N2) nonsquamous NSCLC randomly received (1:1) induction therapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) plus bevacizumab (15 mg/kg) intravenously every 3 weeks for three cycles (arm A) or concurrent TRT (45 Gy in 25 fractions) (arm B) followed by surgery. 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 (RECIST) version 1.1, the pathological complete remission (pCR) rate, feasibility and toxicity. Results: Eighty-eight patients were randomly assigned (each arm, n = 44) between October 2013 and June 2017 and 82 (arm A, n = 42; arm B, n = 40) were treated. Patient demographics were balanced between the two arms. The percentage of patients who received induction therapy followed by surgery was 88.1% (37/42) in arm A and 92.5% (37/40) in arm B. The complete resection rate was 81.1% (30/37) in arm A, and 91.9% (34/37) in arm B. The 2-year PFS rate was 36.8% (95% CI: 22.4-51.2) in arm A, and 50.0% (95% CI: 33.8-64.2) in arm B. The 2-year OS rate was 80.5% (95% CI: 64.7-89.7) in arm A, and 80.0% (95% CI: 64.0-89.5) in arm B. The ORR was 50.0% (21/42) in arm A and 60.0% (24/40) in arm B. The pCR rate was 8.1% (3/37) in arm A and 10.8% (4/37) in arm B. Grade 3 or 4 toxicities occurred during induction therapy in 35.7% of the patients in arm A and 22.5% of the patients in arm B. Grade 3 or 4 surgical complications occurred in 21.4% of the patients in arm A and 20.0% of the patients in arm B. Although no fatal toxicity was observed during induction therapy in either arm, two patients in arm A died after surgery due to bronchopleural fistula. Conclusions: The 2-year PFS rate in arm B was higher than that in arm A. Fatal surgical complications were only observed in arm A. Therefore, we chose pemetrexed-cisplatin plus concurrent thoracic radiation therapy as the investigational induction treatment strategy for a future phase III study. Clinical trial information: 000011941.