Concurrent/sequential versus sequential immune checkpoint inhibition in inoperable large stage III non-small cell lung cancer patients treated with chemoradiotherapy: a prospective observational study

• Published in: Journal of cancer research and clinical oncology Vol. 149; no. 10; pp. 7393 - 7403
• Main Authors: Käsmann, Lukas, Eze, Chukwuka, Taugner, Julian, Nieto, Alexander, Hofstetter, Kerstin, Kröninger, Sophie, Guggenberger, Julian, Kenndoff, Saskia, Flörsch, Benedikt, Tufman, Amanda, Reinmuth, Niels, Duell, Thomas, Belka, Claus, Manapov, Farkhad
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2023; Springer Nature B.V
• Subjects: Cancer Research; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemoradiotherapy; Chemotherapy; Hematology; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Internal Medicine; Lung cancer; Lung Neoplasms - drug therapy; Medicine; Medicine & Public Health; Metastases; Nivolumab - therapeutic use; Non-small cell lung carcinoma; Observational studies; Oncology; PD-1 protein; PD-L1 protein; Pneumonitis; Radiation therapy; Small cell lung carcinoma; Sequence; NSCLC; Durvalumab; Nivolumab; Chemoradiation
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-04654-w

Purpose/aim The international standard for patients with large inoperable stage III NSCLC is durvalumab consolidation after concurrent chemoradiotherapy (CRT). In this single centre observational study based on individual data, we prospectively evaluated the role of concurrent/sequential versus sequential immune checkpoint inhibition (ICI). Methods and patients In total, 39 stage III NSCLC patients were prospectively enrolled, 11 (28%) patients were treated with simultaneous and consolidation therapy with PD-1 inhibition (nivolumab) (SIM-cohort) and 28 (72%) patients received PD-L1 inhibition (durvalumab) as consolidation treatment up to 12 months after the end of CRT (SEQ-cohort). Results For the entire cohort, median progression-free survival (PFS) was 26.3 months and median survival (OS), locoregional recurrence-free survival and distant metastasis-free survival were not reached. For the SIM-cohort, median OS was not reached and PFS was 22.8 months, respectively. In the SEQ-cohort, neither median PFS nor OS were reached. After propensity score matching, PFS at 12/24 months were 82/44% in the SIM-cohort and 57/57% in the SEQ-cohort ( p  = 0.714), respectively. In the SIM-cohort, 36.4/18.2% of patients showed grade II/III pneumonitis; in the SEQ-cohort 18.2/13.6% after PSM ( p  = 0.258, p  = 0.55). Conclusion Both concurrent/sequential and sequential ICI show a favorable side effect profile and promising survival in treated patients with inoperable large stage III NSCLC. Concurrent ICI showed a numerical non-significant improvement regarding 6- and 12-months PFS and distant control compared to sequential approach in this small study. However, concurrent ICI to CRT was associated with a non-significant moderate increase in grade II/III pneumonitis.