A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Combination of Bevacizumab (NSC-704865) in Patients With Inoperable Locally Advanced Stage III Non-Small-Cell Lung Cancer: SWOG S0533

The incorporation of bevacizumab with concurrent chemoradiotherapy (CRT) in the treatment of locally advanced nonesmall-cell lung cancer (NSCLC) could improve efficacy in this disease stage. In this trial we accrued patients in 2 strata (high and low risk for hemoptysis) and in 3 separate cohorts depending on the timing of the bevacizumab. Bevacizumab could not be safely integrated or effectively combined with CRT in inoperable NSCLC patients. Future trials combining bevacizumab and CRT are not warranted. Background: The aim of this trial was to determine feasibility of incorporating bevacizumab (B) into concurrent chemoradiotherapy (CRT) for locally advanced nonesmall-cell lung cancer (NSCLC). Patients and Methods: Patients with unresectable stage III NSCLC, performance status of 0 to 1, and adequate organ function were accrued in 2 strata, low-and high-risk (squamous histology, hemoptysis, tumor with cavitation and/or adjacent to a major vessel). Cohort 1 patients received cisplatin 50 mg/m(2) days (d) 1 and 8, etoposide 50 mg/m(2) (d 1-5) for 2 cycles concurrent with radiotherapy (64.8 Gy) followed by docetaxel (D) 75 mg/m(2) and B 15 mg/kg for 3 cycles. If safety was established, then accrual would continue to cohort 2 (B, d 15, 36, 57) and then subsequently to cohort 3 (B, d 1, 22, 43). Results: Twenty-nine patients (17 low- and 12 high-risk) registered to cohort 1. Twenty-six patients (including 4 squamous, 1 adenosquamous) were assessable. Twenty-five completed CRT. Grade 3/4 toxicities during CRT included acceptable rates of hematologic toxicity, esophagitis, and pneumonitis. Of 21 assessable for safety with D/B consolidation, major adverse events were pneumonitis (2 Grade 3) and 2 episodes of fatal hemoptysis in the high-risk group, resulting in closure of this stratum. The low-risk stratum subsequently closed because of slow accrual. Median overall survival was 46 months for low-risk and 17 months for high-risk strata. Conclusion: Bevacizumab was not safely integrated into CRT for stage III NSCLC in patients considered at high risk for hemoptysis. In lower risk patients, data are insufficient to determine safety or efficacy. (C) 2015 Elsevier Inc. All rights reserved.