OA01.07 Updated Results of a Phase II Trial of Concurrent Chemoradiation with Consolidation Pembrolizumab in Patients with Unresectable Stage III NSCLC

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 updated results of a phase 2 trial of consolidation pembrolizumab [PD-1 inhibitor] following concurrent CRT in patients with unresectable stage III NSCLC. After completion of CRT with carboplatin/paclitaxel, cisplatin/etoposide, or cisplatin/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. 93 pts enrolled [92 eligible for efficacy analysis]. Median f/u was 18.6 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 22.4 months (95% CI 17.9-NR). Median OS was NR (95% CI 22.4-NR), and the estimates of 1-yr and 2-yr OS were 81% and 61.9% respectively. Median PFS was 17 months (95% CI 11.9-NR). 12, 18, and 24-month PFS were 60.2%, 49.9%, and 44.6% 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 G≥2 pneumonitis, the median time was 8.4 wks [1.1-48.3]. No other G 3/4 toxicities exceeded 5% except dyspnea (5.4%). 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. These data will be updated further prior to the World Conference on Lung Cancer Meeting.