A phase I safety and feasibility study of neoadjuvant chemoradiation plus pembrolizumab followed by consolidation pembrolizumab in resectable stage IIIA non-small cell lung cancer.

Abstract

9009 Background: Patients (pts) with resectable stage IIIA non-small cell lung cancer (NSCLC) have high rates of recurrence despite concurrent chemoradiation (CRT) followed by surgery. Immune checkpoint inhibitor consolidation has improved outcomes in unresectable stage III pts. Here we report the addition of concurrent neoadjuvant pembrolizumab (P) to CRT in stage IIIA patients to determine the safety and feasibility of this approach. Methods: Pts with stage IIIA NSCLC deemed resectable by a thoracic surgeon received neoadjuvant CRT consisting of cisplatin, etoposide, and concurrent P (200mg every 3 weeks x 3) with 45 Gy in 25 fractions. Pts without progression underwent resection followed by 6 months of consolidation P. The primary objective was feasibility and safety (defined as ≤30% grade 3 or higher pulmonary toxicity or any grade 4/5 nonhematologic toxicity). Ten pts were to be enrolled in Part 1, and if 2 or fewer pts had events then an additional 10 pts were to be enrolled. Secondary objectives were progression free survival (PFS), overall response rate (ORR), and pathologic complete response rate (pCR). Results: The median age of 9 enrolled pts was 66 years (range 49-76). 67% were female. 8 pts were assessable for radiographic response with an ORR of 75%. One pt came off study for progression prior to surgery and one had pleural metastases found during surgery so resection was aborted. Six pts underwent complete resection with a pCR rate of 67% (4/6). Consolidation P was started on 4 pts, with 3 completing treatment and 1 declined further treatment after 3 cycles. Median follow-up is 19.6 months and median PFS has not been reached. None of the patients who underwent resection have recurred. Serious adverse events were reported in all 9 pts with most significant being 2 grade 5 events: 1 due to pneumocystis pneumonia after resection but prior to consolidation, and 1 due to cardiac arrest during the neoadjuvant phase. Grade 3 events included 1 episode each of pneumonitis, bronchopleural fistula, acute kidney injury, colon perforation, and febrile neutropenia. Conclusions: The addition of P to neoadjuvant CRT in resectable stage IIIA pts resulted in a high pCR rate at resection. Although the relationship between grade 5 events and the addition of P was not clear, the stopping rule for infeasibility was met. As other larger studies are underway, the trial was halted rather than amended. This investigator initiated trial was funded by Merck. Clinical trial information: NCT02987998.