Randomized phase II clinical trial of cisplatin/carboplatin and etoposide (CE) alone or in combination with nivolumab as frontline therapy for extensive-stage small cell lung cancer (ES-SCLC): ECOG-ACRIN EA5161.

9000 Background: Immune checkpoint inhibition is now given in combination with chemotherapy for first line (1L) therapy of extensive stage small cell lung cancer (ES-SCLC). We conducted a randomized phase II study of nivolumab (anti-PD1) in combination with platinum-etoposide (CE) as 1L treatment for patients with ES-SCLC (EA5161, NCT03382561). Methods: Patients with measurable (RECIST v1.1) ES-SCLC, ECOG performance status 0 or 1, who had not received prior systemic treatment for ES-SCLC were enrolled. Patients were randomized 1:1 to nivolumab 360 mg + CE every 21 days for 4 cycles followed by maintenance nivolumab 240 mg every 2 weeks until progression or up to 2 years (arm A) or CE every 21 days for 4 cycles followed by observation (arm B). Prophylactic cranial irradiation (PCI) was permitted at the investigator’s discretion. Investigator’s choice of cisplatin or carboplatin was allowed across both arms. The primary endpoint was PFS in eligible and treated patients. Secondary endpoints included OS, ORR, and safety. Adverse events (AEs) were graded per NCI-CTCAE v4.0. Results: This study was activated in May 2018 and completed accrual in December 2018. 160 patients were enrolled. Baseline characteristics were well balanced between arms. In the ITT population (n = 160), nivolumab + CE significantly improved the PFS compared to CE with HR 0.65 (95% CI, 0.46, 0.91; p = 0.012); mPFS 5.5 versus 4.6 months, respectively. Secondary endpoint of OS was also improved with nivolumab + CE versus CE with HR 0.67 (95% CI, 0.46, 0.98; p = 0.038); mOS 11.3 versus 8.5 months. Among patients who initiated study therapy, nivolumab + CE significantly improved the PFS compared to CE with HR 0.68 (95% CI, 0.48, 1.00; p = 0.047); mPFS 5.5 versus 4.7 months, respectively; in this population, OS was also improved with nivolumab + CE versus CE with HR 0.73 (95% CI, 0.49, 1.11; p = 0.14); mOS 11.3 versus 9.3 months. The ORR was 52.29% versus 47.71%. The incidence of treatment-related grade 3/4 AEs was 77% versus 62% and AEs leading to discontinuation 6.21% versus 2.07%. Ten patients remain on maintenance nivolumab. Lethal adverse events independent of treatment were similar between the two arms (9 in arm A; 7 in arm B). Conclusions: The addition of nivolumab to CE as 1L treatment for ES-SCLC significantly improved PFS and OS. No new safety signals were observed. Clinical trial information: NCT03382561.