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

Abstract

e19007 Background: There are only limited data regarding the use of anti-VEGF therapy in recurrent NSCLC and no data in NSCLC pts previously treated with bevacizumab. 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 and measurable NSCLC, 1 or 2 prior regimens, PS0–2, all histologic sub-types, BP ≤ 140/90, treated brain metastases are eligible. Pts on anti-coagulants are allowed. Pts with hemorrhage within 4 weeks are excluded. Pts start on cediranib 30mg daily followed 7 days later by pemetrexed at 500 mg/m2 every 21 days and cediranib daily. The study consists of two cohorts- cohort A (no prior bevacizumab) and cohort B (prior bevacizumab). Planned accrual is 37 pts each cohort. Consenting pts will undergo FLT PET scans and blood draw for circulating tumor cells before therapy, 1 week after cediranib, and after 1 cycle of the combination. Results: 33 pts have started therapy, (Cohort A- 20, Cohort B- 13), median age- 60, males- 56%, ever smokers- 88%, adenocarcinoma- 64%, squamous- 12%, brain mets- 27%, 1 prior regimen- 52%, PS0–1- 88%. Median cycles- 4 (range- 0–15). Grade 3/4 toxicities- neutropenia- 7pts, febrile neutropenia- 1pt, fatigue-7pts, diarrhea- 3pts, hypertension- 1pt, anorexia- 2pts, cardiac ischemia- 1pt, bronchopleural fistula- 1pt, esophagitis- 1pt. No major hemorrhage. Of the 17 pts who received cediranib for ≥ 4 cycles, 71% required dose reduction and of the 18 pts who received pemetrexed for ≥ 4 cycles, 22% required dose reduction. 31 pts (Cohort A- 19, Cohort B- 12) are response evaluable. Confirmed response rate is 16%(90% CI- 0.08–0.30) (Cohort A- 10%, Cohort B- 25%) and disease control rate (response+stable disease) is 71% (90% CI-0.56–0.82) (Cohort A- 74%, Cohort B- 67%). 8 of 9 pts who had FLT PET scans had a 20% or greater decline in standard uptake value after 1 week of cediranib alone. Conclusions: Cediranib and pemetrexed combination is tolerable. Efficacy has been observed with the combination in recurrent NSCLC pts, including those previously treated with bevacizumab. Accrual to this trial is ongoing. [Table: see text]