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NSCLC accounts for 80% of all lung cancer diagnoses, and approximately a third of patients present with locally advanced (stage III) disease [1]. The optimal therapy for fit patients with unresectable and/or inoperable stage III disease has evolved over the last three decades from radiation alone to sequential chemoradiation (CRT) to concurrent CRT followed by checkpoint inhibitor therapy (CPI). The recently reported PACIFIC trial generated a paradigm shift in the treatment of such patients, with a 3-year overall survival (OS) of 57% for patients receiving consolidation durvalumab compared with 43.5% for those receiving placebo [2–4]. Similar outcomes were reported with consolidation pembrolizumab in a Hoosier Cancer Research Network (HCRN) Phase II Trial [5]. In this article, we explore key clinical challenges that arise when treating patients with consolidation CPI after CRT for patients with stage III NSCLC; namely, the management of CPI-related pneumonitis, timing of consolidation CPI and their role in patients with PD-L1 TPS <1% and distinguishing local progression versus pseudoprogression.

Practical challenges in patients with stage III NSCLC receiving checkpoint inhibitors after chemoradiation