GASTO 1001: a Phase 2 Trial of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin in Patients with Unresectable Stage III Lung Adenocarcinoma
Unresectable stage III NSCLC is often treated with concurrent chemoradiotherapy with poor results. On the other hand, bevacizumab has showed efficacy in advanced nonsquamous lung cancer.a The aim of the phase 2 trial presented by Wang and colleaguesb was to assess the efficacy and safety of induction bevacizumab (Bev) plus pemetrexed (500 mg/m2) and carboplatin (AUC = 5) (Bev-PC) followed by surgery for patients with unresectable, stage III lung adenocarcinoma who had received no previous chemotherapy, radiotherapy, surgery, or biologic therapy for lung cancer. Neoadjuvant therapy was administered every 3 weeks for 4 cycles. Surgery was scheduled 3-4 weeks after the last neoadjuvant therapy and patients’ resectability was assessed by a medical team, including thoracic surgeons, medical oncologists, and radiologists. The primary endpoint was resectability rate, with secondary endpoints including perioperative complications, event-free survival (EFS), and overall survival (OS).
At the time of this presentation, 42 patients had enrolled and received Bev-PC. Grade 3 or 4 neoadjuvant-related adverse events included fatigue in 5 patients, neutropenia in 4, hypertension in 1, and thrombocytopenia in 1. The adverse events thought to be related to bevacizumab were epistaxis in 3 patients and hypertension in 2 patients (grade 1 in 1; grade 3 in 1). Complete response was achieved in 1 patient, partial response in 22, stable disease in 17, and progressive disease in 2. After neoadjuvant therapy, 31 patients underwent surgery, with pneumonectomy in 11. R0 resection was achieved in 22 patients. Postoperative complications included pneumonia (4 patients), atelectasis (2), bronchial stump insufficiency (1), empyema (1), subcutaneous emphysema (2) and arrhythmia (1). No perioperative hemorrhage events, thromboembolic events or wound-healing problems were observed. No patient died in the perioperative period. The median EFS was 15.4 months, and the 1-year EFS was 56.1%. OS data were not presented. The authors concluded that neoadjuvant treatment with Bev-PC followed by surgery appears to be a feasible and safe approach in patients with unresectable stage III lung adenocarcinoma.
- Villaruz LC, Socinski MA. Curr Oncol Rep. 2015;17:448. Doi: 10.1007/s 11912-015-0448-y.
- Wang S-Y, et al. ASCO 2015. Abstract 7528.