Randomized phase II trial of pemetrexed-cisplatin plus bevacizumab or thoracic radiotherapy followed by surgery for stage IIIA (N2) nonsquamous non–small cell lung cancer

Background Personalized Induction Therapy-1 is a multicenter, randomized phase II selection design trial of the efficacy and safety of platinum-doublet induction chemotherapy plus angiogenesis inhibitors/concurrent thoracic radiotherapy (TRT) followed by surgery for stage IIIA (N2) nonsquamous non–small cell lung cancer (NSCLC). Methods Patients with pathologically proven stage IIIA (N2) nonsquamous NSCLC were assigned at random to 1 of 2 arms. Patients received (1:1) induction therapy with pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 plus bevacizumab 15 mg/kg intravenously every 3 weeks for 3 cycles (bevacizumab arm) or concurrent TRT (45 Gy in 25 fractions; TRT arm) before surgery. The primary endpoint was the 2-year progression-free survival (PFS) rate. Results Eighty-two patients were treated, including 42 in the bevacizumab arm and 40 in the TRT arm. Thirty-eight patients (90%) in the bevacizumab arm and 37 patients (93%) in the TRT arm underwent surgery. The objective response rates in the 2 groups were 50% and 60%, respectively (P = .36). The 2-year PFS and overall survival rates were 37% (95% confidence interval [CI], 22.4%-51.2%) and 50% (95% CI, 33.8%-64.2%) (hazard ratio [HR], 1.34; P = .28), respectively, and 81% (95% CI, 64.7%-89.7%) and 80% (95% CI, 64.0%-89.5%) (HR, 1.10; P = .83), respectively. Although grade 5 toxicity did not occur during induction therapy, 2 patients in the bevacizumab arm died due to bronchopleural fistula. Conclusions Although not significant, the 2-year PFS rate was higher in the TRT arm than in the bevacizumab arm. Fatal surgical complications were observed only in the bevacizumab arm. Therefore, pemetrexed-cisplatin with concurrent TRT was chosen as the investigational induction treatment strategy for future phase III trials.