Patients with platinum-pretreated SCLC may benefit from combination use of cediranib, an oral VEGF inhibitor, and olaparib, a PARP inhibitor.
Olaparib (Lynparza), a poly (ADP-ribose) polymerase (PARP) inhibitor, has demonstrated clinical efficacy in patients with various types of advanced solid tumors who carry a germline BRCA mutation.1 Researchers explored the antitumor activity of cediranib (Recentin), an oral vascular endothelial growth factor (VEGF) receptor inhibitor, combined with olaparib, a PARP inhibitor, in patients with advanced solid tumors, including patients with SCLC.2
This phase 2, multicenter, 2-stage study enrolled patients with metastatic SCLC who were previously treated in the advanced setting with ≥1 platinum-based chemotherapy regimens. Patients received cediranib 30 mg by mouth once daily plus olaparib 200 mg by mouth twice daily until disease progression or unacceptable toxicity. The study’s primary end point was ORR by RECIST version 1.1. Baseline tumor biopsies were obtained to perform biomarker analyses.2
A total of 25 patients were enrolled in this study, with a median age of 67 years (range, 46-79 years) and a median number of previous therapies of 2 (range, 1-5).2 Most (80%) were platinum-sensitive, and half (52%) had been treated with immunotherapy.2
Among these patients, the ORR associated with cediranib plus olaparib was 28% (95% CI, 10%-46%).2 Among responders, the median DOR was 3.8 months; 6 of 8 responding patients had an objective response that lasted more than 3 months and up to 10.3 months.2 The rate of disease control (complete response plus partial response plus stable disease) was 88% (95% CI, 75%-100%).2 Median PFS was 4.1 months (95% CI, 2.3-6.2 months).2 Median OS was 5.5 months (95% CI, 3.4-not available).2
Grade 3/4 AEs, irrespective of attribution, were observed in 12 of 25 patients (48%).2 Grade 3/4 AEs that occurred in more than 10% of patients were hypertension (21%), fatigue (17%), and weight loss (13%).2
Researchers concluded that the combination of cediranib plus olaparib resulted in promising clinical activity in patients with platinum-pretreated SCLC, with an ORR of 28% in biomarker-unselected patients.2 In some patients, this regimen required prompt initiation of antihypertensives. AEs were manageable overall.2 Analyses of mutation status in homologous recombination DNA repair genes are ongoing to learn whether mutational status correlates with clinical activity.2
1. Caulfield SE, Davis CC, Byers KF. Olaparib: a novel therapy for metastatic breast cancer in patients with a BRCA1/2 mutation. J Adv Pract Oncol. 2019;10:167-174.
2. Kim JW, Hafez N, Soliman HH, et al. Preliminary efficacy data of platinum-pretreated small cell lung cancer (SCLC) cohort of NCI 9881 study: a phase II study of cediranib in combination with olaparib in advanced solid tumors. J Clin Oncol. 2020;38(15_suppl). Abstract 9065.