Beyond Concurrent Chemoradiation: The Emerging Role of PD-1/PD-L1 Inhibitors in Stage III Lung Cancer

• Published in: Clinical cancer research Vol. 24; no. 6; pp. 1271 - 1276
• Main Authors: McCall, Neal S, Dicker, Adam P, Lu, Bo
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research Inc 15.03.2018
• Subjects: Cancer; Cancer therapies; Chemoradiotherapy; Chemotherapy; Clinical trials; Consolidation; Immune checkpoint inhibitors; Immunity; Immunosuppressive agents; Inhibitors; Lung cancer; Medical research; Monoclonal antibodies; Non-small cell lung carcinoma; Patients; PD-1 protein; PD-L1 protein; Platinum; Radiation; Survival; Targeted cancer therapy
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-17-3269

Concurrent chemoradiation (cCRT) with platinum-based chemotherapy is standard-of-care therapy for patients with stage III unresectable non-small cell lung cancer (NSCLC). Although cCRT is potentially curative, 5-year overall survival has hovered around 20%, despite extensive efforts to improve outcomes with increasing doses of conformal radiation and intensification of systemic therapy with either induction or consolidation chemotherapy. PD-1/PD-L1 immune checkpoint inhibitors have demonstrated unprecedented efficacy in patients with stage IV NSCLC. In addition, preclinical and early clinical evidence suggests that chemotherapy and radiation may work synergistically with anti-PD-1/PD-L1 therapy to promote antitumor immunity, which has led to the initiation of clinical trials testing these drugs in patients with stage III NSCLC. A preliminary report of a randomized phase III trial, the PACIFIC trial, demonstrated an impressive increase in median progression-free survival with consolidative durvalumab, a PD-L1 inhibitor, compared with observation after cCRT. Here, we discuss the clinical and translational implications of integrating PD-1/PD-L1 inhibitors in the management of patients with unresectable stage III NSCLC. .