Significance of Immune Checkpoint Inhibitors in Patients with Locally Advanced Non-Small Cell Lung Cancer Treated with Chemoradiotherapy Prior to the Approval of Durvalumab

Background: The standard treatment for patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC) was chemoradiotherapy (CRT). Consolidation therapy with durvalumab, an anti-programmed death ligand-1 antibody, after CRT demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and we investigate the feasibility of concurrent CRT for LA-NSCLC patients based on the PACIFIC criteria. Methods: We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA-NSCLC treated with CRT between January 2012 and June 2018 in clinical practice, based on the PACIFIC criteria. Results: We analyzed a total of 108 consecutive patients ( 81 males and 27 females) who received radical thoracic radiotherapy and concurrent platinum-based chemotherapy. Of those, 105 patients (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41–317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the 2-year survival rate was 63%. Of the 82 patients who relapsed after CRT, 18 patients received treatment with an ICI in the course of treatment. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (2-year survival rate: 87% vs. 41%, respectively; p = 0.001). Conclusion: Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA-NSCLC. The treatment strategy of ICI consolidation therapy for patients with LA-NSCLC and the management of radiation pneumonitis are challenges following the approval of durvalumab.