P3.02c-015 Phase II Trial of S-1/Cisplatin Combined with Bevacizumab for Advanced Non-Squamous Non-Small Cell Lung Cancer: TCOG LC-1202: Topic: Targeted Therapy

S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC) (Ann. Oncol. 2015; 26:1401-8). The addition of bevacizumab significantly improved overall survival (OS) in patients with advanced non-squamous (non-SQ) NSCLC who received carboplatin plus paclitaxel but failed to show an OS advantage in patients who received cisplatin plus gemcitabine. Few studies of bevacizumab have evaluated quality of life (QOL) in patients with non-SQ NSCLC. Chemotherapy-naïve patients with stage IIIB, IV, or recurrent non-SQ NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1, age 20–74 years, and measurable lesions were treated with a 3-week cycle of S-1 40 mg/m2 twice a day on days 1–14, cisplatin 60 mg/m2 on day 8, and bevacizumab 15 mg/kg on day 8, for 4–6 cycles. Patients without progressive disease received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 40 mg/m2 twice a day every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile, and QOL. From June 2013 to January 2015, 39 evaluable patients were enrolled from 8 institutions: 10 women and 29 men; median age 65 (range, 38–74) years; epidermal growth factor receptor positive/anaplastic lymphoma kinase positive: two patients/two patients; performance status 0/1: 22/17; stage IIIB/IV/recurrence: 1/35/3; adeno/large cell/other: 35/1/3. Thirty one patients (80%) completed 4 cycles of induction chemotherapy, and 23 patients (59%) were started on maintenance chemotherapy. Median PFS, OS, and ORR were 7.3 months (95% confidence interval (CI): 5.9–8.7), 21.4 months (95% CI: 14.7–not reached), and 64%, respectively. The worst hematologic and non-hematologic adverse events were as follows (%): grade 3/4 leukopenia: 13/0; neutropenia: 18/5; thrombocytopenia: 0/0; anemia: 0/0; neutropenic fever: 3/0; and hypertension: 28/0; diarrhea: 3/0. QOL data will be presented at the meeting. S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced non-SQ NSCLC in the present trial. Additionally, the response rate is anticipated to be high, and the regimen was well tolerated. Clinical trial information: UMIN000009476.