A phase II first-line study of gemcitabine, carboplatin, and bevacizumab (GCB) in advanced (adv) stage non-squamous non-small cell lung cancer (NSCLC)

Abstract

e19024 Background: B adds to 1st-line paclitaxel/carboplatin (PC) for pts with adv NSq-NSCLC. Gemcitabine/carboplatin (GC) has equivalent efficacy to PC with a different toxicity profile. This study was designed to evaluate toxicities (AEs) of GCB and to estimate survival. Methods: Patients (pts) with untreated adv NSq-NSCLC, with no evidence of CNS metastases were eligible. Pts received G 1000 mg/m2 on d1, 8; C AUC 5 d1; and B 15 mg/kg d1 q21d for up to 6 cycles. B was then continued q21d until disease progression or unacceptable toxicity. Chemo dose reductions were mandated for significant cytopenias. Imaging was every 2 cycles. Results: From 07/06 to 12/08, 48 pts enrolled (accrual complete): 23(48%) men, 19(40%) never smokers, median age 59yo (35–81). One pt died prior to receiving therapy and is not included in the analysis. Median cycle number is 6(0–37). To date, 35 pts (74%) completed ≥ 4 cycles of 3 drugs. Dose reductions occurred in 29(62%) of pts. G3/4 AEs included: neutropenia (47%/17%), thrombocytopenia (11%/15%), and anemia (6%/0%). No pts were hospitalized for neutropenic fever. G3/G4 non-hematologic AEs included dyspnea (6%/2%), bacterial pneumonia (4%/0) hypertension (4%/2%), 1G3 wound dehiscence, 1G4 MI, 1G3 transaminitis and hyperbilirubinemia, 1G3 proteinuria and 1G3 leucocyturia. 1 pt died from hemoptysis with untreated aspergillosis found post-mortem. Other bleeding included 1 case each with G3 epistaxis, hemorrhoidal bleeding and ecchymosis. Common G1/2 AEs included fatigue, hypertension, anemia, constipation, nausea, headaches, transaminitis and epistaxis. In 42 evaluable pts: we saw 7(17%) PRs, and 31(74%) SDs at 1st f/up. 44/47 pts were followed for a median of 10.5mo (3 recently enrolled pts with f/u < 20d - excluded). Median time to first event (progression/death/toxicity requiring discontinuation) was 6.4mo [95%CI 4.6–8.6mo]. 17/44 (38.6%) pts have died with median overall survival (mOS) not reached but preliminarily estimated at 16.7mo [95%CI 13.4mo-inf]. Estimated OS is 73% at 1yr and 32% at 2yrs. Conclusions: Treatment with GCB has an acceptable toxicity profile with promising mOS despite a low RR and frequent dose reductions in a population with a high proportion of non-smokers and women. No significant financial relationships to disclose.