A Prospective Single Arm Phase I/II Study: Ipilimumab and Nivolumab with Thoracic Radiotherapy after Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer

Lung Cancer
02/10/2020

Int J Radiat Oncol Biol Phys. 2020 Sep 28:S0360-3016(20)34303-0. doi: 10.1016/j.ijrobp.2020.09.031. Online ahead of print.

ABSTRACT

PURPOSE: Consolidative thoracic radiotherapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer (ES-SCLC). We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes for patients with ES-SCLC.

MATERIALS AND METHODS: Eligibility required stable disease or better after platinum doublet chemotherapy (CT). Study therapy included consolidative TRT to 30Gy in 10 fractions, targeting residual primary tumor and initially involved regional lymph nodes. Two weeks after TRT, patients received concurrent IPI (3mg/kg) and NIVO (1mg/kg) q3 weeks for 4 doses followed by NIVO monotherapy (480mg) q4 weeks until progression or up to 1 year.

RESULTS: The study enrolled 21 patients, with 6-month PFS of 24% (90% CI: 11%-40%) and a median PFS of 4.5 months (95% CI: 2.7-4.6). The 12-month OS was 48% (95% CI 29%-64%) with a median OS of 11.7 months (95% CI: 4.7-16.0). Fifty-two percent of patients had ≥ 1 possibly related grade 3-4 immune related adverse event (IRAE). Grade 3 pulmonary and GI IRAEs were recorded in 19% and 24% of patients, respectively. Exploratory analysis showed increased cytotoxic T cell (CD3+CD8+) tumor infiltration was associated with favorable PFS (P=0.01) and OS (P=0.02). Reduction in peripheral blood CD3+CD8+ from baseline to after first dose of IPI/NIVO was associated with improved PFS (P=0.02) and OS (P=0.02).

CONCLUSIONS: Consolidative IPI and NIVO after platinum-based CT and TRT demonstrated a toxicity profile consistent with the known AEs attributable to IPI and NIVO. Although the study regimen did not significantly improve PFS, the OS was higher than historic expectations. CD3+CD8+ tumor infiltration and migration may identify patients most likely to have improved outcomes in SCLC.