Phase II Trial of Carfilzomib Plus Irinotecan in Patients with Small Cell Lung Cancer Who Have Progressed on Prior Platinum-Based Chemotherapy.

Highlights •This is the first report of the combination of carfilzomib and irinotecan in relapsed small cell lung cancer. •In this study of 62 adults, irinotecan and carfilzomib was tolerable and provided a 6-month overall survival of 59% in platinum sensitive and 54% in platinum refractory patients. •In small cell lung cancer, the novel combination of irinotecan and carfilzomib provide an excellent treatment option for good performance status patients with relapsed small cell lung cancer regardless of prior sensitivity to platinum combination chemotherapy. Purpose To evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in relapsed small cell lung cancer (SCLC) patients. Patients and Methods SCLC patients who progressed after one platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease (PD) \u3e 90 days after chemotherapy) or refractory (RS) (PD 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. Primary endpoint was 6-month overall survival (OS). Results All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the RS. Overall response rate (ORR) was 21.6% (2.7% complete (CR), 18.9% partial response (PR) in SS (n = 37) and 12.5% (all PR) in RS (n = 25). Disease control rate (DCR) was 68% (SS) and 56% (RS). PFS and OS were 3.6 months (95% CI 2.6 - 4.6) and 6.9 months (95% CI 4.3 - 12.3) in SS, and 3.3 months (95% CI 1.8 – 3.9) and 6.8 months (95% CI 4.1-11) in RS. 29 patients (47%) experienced \u3e grade 3 AE; 8 subjects (12.9%) had grade 4 toxicities. Three treatment related deaths occurred: myocardial infarction (possible), lung infection (possible), sepsis (probable). Conclusion In relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed SCLC patients with PS 0-1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy