Phase II trial of concurrent chemoradiation with consolidation pembrolizumab in patients with unresectable stage III non-small cell lung cancer: Hoosier Cancer Research Network LUN 14-179.

Abstract

8500 Background: Concurrent chemoradiation (CRT) has been the standard Rx for pts with unresectable stage III NSCLC. A recent phase III trial (PACIFIC) of consolidation durvalumab [PDL-1 inhibitor] demonstrated improved median PFS vs. placebo (16.8 vs. 5.6 mo, HR 0.52, p < 0.001). 12-mo (55.9% vs. 35.3%) and 18-mo (44.2% vs. 27%) PFS were also improved. Toxicity was manageable with a grade 3-4 pneumonitis rate of 3.4%, and 4 patients experienced grade 5 pneumonitis. We report the results of a phase 2 trial of consolidation pembrolizumab [PD-1 inhibitor] following concurrent CRT in patients with unresectable stage III NSCLC. Methods: After completion of CRT with carbo/pac, cis/etop, or cis/pemetrexed + 59-66.6 Gy XRT, those pts w/o PD after 4-8 weeks off CRT received pembro 200 mg IV q3wk for up to 1 yr. The primary endpoint was time to metastatic disease or death [TMDD]. Key secondary endpoints included PFS, OS, and toxicity. Results: 93 pts enrolled [92 eligible for efficacy analysis]. Median f/u was 16.4 mo and median age 66 (45-84). 64.1% male and 35.9% female. Stages were 59.8% IIIA and 40.2% IIIB. 55.4% non-SqCC and 43.5% SqCC with 1 mixed histology. 94.6% were current/former smokers. Chemo regimens included carbo/pac (71.7%), cis/etop (26.1%), cis/pemetrexed (2.2%). Median number of cycles of pembro was 13.5 [1-19]. 16% received < 4 cycles; 84% received ≥ 4 cycles; 37% completed 1 yr pembro. Median TMDD was not reached (95% CI 18.7-NR), but the estimates of 1-yr and 2-yr OS were 80.5% and 68.7% respectively. Median PFS was 15.4 months (95% CI 10.4-NR). 12, 18, and 24-month PFS were 59.9%, 49.5%, and 45.4% respectively. 16 (17.2%) pts developed G≥2 pneumonitis, 5 (5.4%) had G3-4 pneumonitis. There was 1 pneumonitis-related death. In those developing pneumonitis, the median time was 8.4 wks [1.1-48.2]. No other G 3/4 toxicities exceeded 5% except dyspnea (5.4%). Conclusions: Consolidation pembrolizumab following CRT substantially improves TMDD and PFS compared with historical controls. Prelim OS data is promising and suggests a substantial gain in outcomes of patients with stage III NSCLC is possible with consolidation pembrolizumab. Clinical trial information: NCT02343952.