Abstract

Standard treatment for patients with locally advanced (LA) non-small cell lung cancer (NSCLC) was concurrent chemoradiotherapy (CRT) with 40-70% of 2-year overall survival (OS). Immune checkpoint inhibitors (ICIs) have been shown efficacy in advanced or recurrent NSCLC and approved on December 2015 in Japan. After that, the ICI durvalumab was approved as maintenance therapy after concurrent CRT even in unresectable LA-NSCLC on July 2018 in Japan. To investigate the feasibility of concurrent CRT for LA-NSCLC patients and efficacy of ICI treatment for the relapsed patients after CRT, we assessed consecutive LA-NSCLC patients treated with concurrent CRT between July 2013 and June 2018 (before durvalumab approval), retrospectively. 108 eligible patients (81 males and 27 females with median age of 65 years old, including 7 patients with targeted mutations; 2 EGFR, 4 ALK and 1 ROS1) were analyzed. All patients received radical thoracic radiotherapy using 3D planning system and concurrent with platinum-based chemotherapy. 79 (73%) received one or two cycles of consolidation chemotherapy of same regimen. 105 (97%) patients completed planned radiotherapy, and radiation pneumonitis was observed in 93 (85%) patients with median 130 (range, 41-317) days from initiation of radiation to onset. 74 (69%) patients met the PACIFIC criteria and were considered to be eligible for durvalumab. The overall response rate was 64% and the progression free survival was 10.3 (95% CI, 8.4–12.2) months. The OS was 41.8 (95%CI, 20.1-63.5) months and 2-year OS were 63%. Of the 82 patients who relapsed after CRT, 18 patients received ICI treatment (14 nivolumab, 3 pembrolizumab, 1 atezolizumab) in the course of treatment. Patients who received ICI after relapse had significantly better survival than those who did not receive ICI (2-year OS, 87% vs. 41%; p=0.001). Concurrent CRT using platinum-based regimen was considered effective treatment with acceptable toxicity for LA-NSCLC patients. The efficacy of ICI treatment has been shown in patients with relapse after concurrent CRT in LA-NSCLC, and indication with durvalumab maintenance therapy is expected to further improve the prognosis in patients with LA-NSCLC. The optimal use timing of ICI treatment for patients with LA-NSCLC should be considered.

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