Long-term outcomes are still poor for patients with locally advanced NSCLC with about 60% of the stage IIIA patients recurring in 3 years, despite chemoradiation with or without surgery. Immune checkpoint inhibitor consolidation has improved outcomes in unresectable stage III patients. Therefore, the addition of concurrent neoadjuvant pembrolizumab to chemoradiation is an attractive target of investigation.

In a poster presentation at the virtual meeting of the American Society of Clinical Oncology, researches from the Cleveland Clinic Foundation (Cleveland, USA) and the Perlmutter Cancer Center (New York, USA) rereported the results of a phase 1 trial exploring the feasibility and safety of neoadjuvant chemoradiation plus pembrolizumab followed by consolidation pembrolizumab. A total of 9 patients with stage IIIA, resectable  NSCLC were enrolled. They received neoadjuvant chemoradiation consisting of cisplatin, etoposide, and concurrent pembrolizumab (200mg every 3 weeks x 3) with 45 Gy in 25 fractions. Patients without progression underwent resection followed by 6 months of consolidation pembrolizumab.

Six patients underwent complete resection with a pathologic complete response rate (pCR) of 67% (4/6). Consolidation pembrolizumab was started on 4 patients, with 3 completing treatment and 1 declined further treatment after 3 cycles.

Median follow-up was 19.6 months and median progression-free survival (PFS) had not yet been reached at data cut-off (6 month PFS 55.6%). None of the patients who underwent resection have recurred. Serious adverse events were reported in all 9 patients 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.

The addition of pembrolizumab to neoadjuvant chemoradiation in resectable stage IIIA NSCLC patients resulted in a high pCR rate at resection, warranting further study, the researchers conclude. Larger studies are underway.

Lemmon C, et al. ASCO 2020 virtual meeting, abstract 9009.