Cediranib, a VEGF receptor 1, 2, and 3 inhibitor, and pemetrexed in patients (pts) with recurrent non-small cell lung cancer (NSCLC).

Abstract

7564 Background: The role of anti-VEGF therapy in recurrent NSCLC is unclear. We are currently conducting a phase II trial evaluating cediranib, an oral inhibitor of VEGFR 1, 2 and 3, and pemetrexed in recurrent NSCLC pts who may or may not have previously received bevacizumab. Methods: Pts with progressive NSCLC following 1 or 2 prior regimens and with any histologic sub-type were eligible. Pts on anti-coagulants and with treated brain mets were allowed. Pts received cediranib 30mg daily. 1 week after starting cediranib, pts received pemetrexed 500 mg/m2 every 21 days. The study consists of two cohorts- A (no prior bevacizumab) and B (prior bevacizumab). Planned accrual is 37 pts each cohort. Accrual to cohort A is completed. Consenting pts underwent blood draw for circulating tumor cells (CTCs) and circulating endothelial cells (CECs) before therapy, 1 week after cediranib was commenced, and after 1 cycle of the combination. Results: 38 pts were enrolled in cohort A. Median age- 62, males- 50%, ever smokers- 92%, squamous- 18% (7 patients), brain mets- 34%, 2 prior regimens- 42%. Median cycles- 4 (range: 0-26). Grade 3/4 toxicities- neutropenia- 14%, febrile neutropenia- 5%, fatigue-22%, diarrhea- 14%, infection- 8%. One patient each developed pulmonary hemorrhage, cardiac ischemia and cerebrovascular event. Three deaths were deemed related to drug related toxicities. Response rate is 29% (95% CI: 17%-45%) and disease control rate (response+stable disease) is 74% (58%-85%). Median PFS is 5.6 (4.4-6.8) months and median survival is 11 (5.8-16.6) months. Efficacy parameters for squamous versus non-squamous were- Response rate- 0% vs. 35%, PFS- 3.7 vs. 5.7 months, survival 5.2 vs. 11.5 months. Among 18 pts with available data, 60% had decrease in CTCs and 31% of the patients had declines in CECs. There was no significant association between declines in CTCs or CECs and PFS. Conclusions: 1.The combination of cediranib and pemetrexed is tolerable. 2. The response rate of 29% (35%-non-squamous) and the median PFS of 5.6 (5.7-non-squamous) months are very promising. 3. Though the numbers are small, this combination is ineffective in recurrent squamous cell patients. 4. Enrollment to cohort B is ongoing.