Cediranib (AZD2171) for the treatment of recurrent small cell lung cancer (SCLC): A California Consortium phase II study (NCI # 7097)

Abstract

8078 Background: Cediranib is a highly potent inhibitor of VEGFR-1, -2 and -3 tyrosine kinases. We conducted a phase II study to evaluate its safety and efficacy in relapsed/recurrent SCLC. Methods: Patients with progression of SCLC following prior platinum-based chemotherapy (1 prior regimen only), ECOG performance status of 0, 1 or 2, and adequate organ functions were were treated with cediranib on a continuous, once-daily oral schedule (4-week cycles). Those with brain metastasis were excluded. Primary endpoint was response rate and the Simon-two stage design was utilized (estimated sample size = 37 pts). Results: Twenty five patients were enrolled. Baseline characteristics: median age 61 (36–86); male 13; and PS 0/1- 8/12 pts. Twelve patients were accrued to the first stage with the starting dose of 45 mg QD. Since 7 out of 12 patients failed to complete first cycle due to adverse events, the trial was amended to reduce the starting dose to 30 mg QD. Thirteen patients were treated at this dose level, as planned. Median of 2 cycles was administered (1–7). Salient grade 3 toxicities were fatigue (gr 3 - 4, gr 4- 2), diarrhea (1), skin rash (1), proteinuria (2), transaminitis (1), muscle weakness (1) and hypertension (1). One unconfirmed PR and 8 with SD were noted. Median PFS was approximately 8 weeks. Peripheral blood was evaluated serially for VEGF concentration and circulating endothelial cell (CEC) counts. A stark increase in CECs was noted at progression in several patients. Divergent results were observed with serial plasma VEGF levels, with several patients showing increasing levels while on therapy, however there was no clear correlation with anti-cancer effect. The response rate did not meet pre-defined target (20%) to continue full accrual to the study. Conclusions: The originally recommended dose of cediranib of 45 mg QD was not feasible in the patient population studied. The modest anti-cancer activity of cediranib (30 mg QD) supports its further evaluation as part of combination regimens, but not as monotherapy for recurrent SCLC. Supported by NCI N01-CM-62209, N01-CM-62201 & NO1 62205 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca AstraZeneca