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.

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.

Five years after PACIFIC: update on multimodal treatment efficacy based on real-world reports.

INTRODUCTION: The growing body of real-life data on maintenance treatment with durvalumab suggests that immunological markers of the cancer host interplay may have significant effects on the efficacy of multimodal therapy in patients with unresectable stage III NSCLC. AREAS COVERED: We summarize real-world clinical data regarding this new tri-modal approach and report on potential biomarker landscape. EXPERT OPINION: The obvious question posed in this context of a very heterogeneous inoperable stage III NSCLC disease is: How can we augment an ability to predict checkpoint inhibition success or failure? Which tools and biomarkers, which clinical metadata and genetic background are relevant and feasible? No single biomarker will ever fully dominate the unresectable stage III NSCLC space, so we advocate multilevel and multivariate analysis of biomarkers. In this particular opinion piece, we explore the impact of PD-L1 expression on tumor cells, neutrophil-to-lymphocyte ratio, EGFR and STK11 mutational status, interferon-gamma signature, and tumor-infiltrating lymphocytes among others.