Abstract

Simple SummaryConcurrent platinbased chemoradiotherapy followed by maintenance treatment with the PD-L1 inhibitor durvalumab is the new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with chemoradiotherapy to those treated with chemoradiotherapy and durvalumab (CRT-IO) in the real-world setting. Median follow-up for entire cohort was 33.1 months and median overall survival was 27.2 months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, local-regional-progression-free-survival, progression-free, and overall survival (PFS, OS) were significantly improved compared to the historical cohort of conventional chemoradiotherapy patients. This real-world analysis demonstrated that durvalumab after chemoradiotherapy (CRT) led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.Concurrent chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is a new standard of care for inoperable stage III NSCLC. The present study compares the oncological outcome of patients treated with CRT to those treated with CRT and durvalumab (CRT-IO) in the real-world setting. The analysis was performed based on the retro- and prospectively collected data of 144 consecutive inoperable stage III NSCLC patients treated between 2011–2020. Local-regional-progression-free-survival (LRPFS—defined as progression in the mediastinum, hilum and/or supraclavicular region at both sites and the involved lung), progression-free survival (PFS), and overall survival (OS) were evaluated from the last day of thoracic radiotherapy (TRT). Median follow-up for the entire cohort was 33.1 months (range: 6.3–111.8) and median overall survival was 27.2 (95% CI: 19.5–34.9) months. In the CRT-IO cohort after a median follow-up of 20.9 (range: 6.3–27.4) months, median PFS was not reached, LRPFS (p = 0.002), PFS (p = 0.018), and OS (p = 0.005) were significantly improved vs. the historical cohort of conventional CRT patients. After propensity-score matching (PSM) analysis with age, gender, histology, tumor volume, and treatment mode, and exact matching for T-and N-stage, 22 CRT-IO patients were matched 1:2 to 44 CRT patients. Twelve-month LRPFS, PFS, and OS rates in the CRT-IO vs. CRT cohort were 78.9 vs. 45.5% (p = 0.002), 60.0 vs. 31.8% (p = 0.007), and 100 vs. 70.5% (p = 0.003), respectively. This real-world analysis demonstrated that durvalumab after CRT led to significant improvement of local-regional control, PFS, and OS in PD-L1 expressing inoperable stage III NSCLC patients compared to a historical cohort.

Highlights

  • Inoperable stage III non-small-cell lung carcinoma (NSCLC) represents a complex and heterogeneous disease with significant differences regarding patient, tumor, and treatment characteristics [1,2,3,4,5,6,7,8]

  • The entire cohort consisted of 144 consecutive NSCLC patients with inoperable stage IIIA-C (UICC 8th edition) NSCLC treated before and after the durvalumab approval

  • The predominant concurrent chemotherapy regimen administered in 99 (68.8%) patients consisted of cisplatin given intravenously at a dose of 20 mg/m2 on days 1–4 and oral vinorelbine (Navelbine) 50 mg/m2 on days 1, 8, and 15, every 4 weeks for two courses according to GILT study [38]

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Summary

Introduction

Inoperable stage III non-small-cell lung carcinoma (NSCLC) represents a complex and heterogeneous disease with significant differences regarding patient, tumor, and treatment characteristics [1,2,3,4,5,6,7,8]. Several phase III trials including RTOG 73-01, CALGB 8433, RTOG 9410, and RTOG 0617 established platinum-based concurrent chemoradiotherapy (CRT) to a cumulative dose of 60 Gy without induction and consolidation chemotherapy as the most effective strategy accompanied by a moderate acute toxicity profile [14,15,16,17,18] This treatment paradigm was modified after the pivotal phase III PACIFIC trial showing an unprecedented improvement of progression-free survival (PFS) and overall survival (OS) after consolidation therapy with the Programmed death-ligand 1 (PD-L1) inhibitor durvalumab following platinumbased CRT [19,20,21]. Based on the results of a post-hoc analysis, the European Medicines Agency (EMA) approved durvalumab consolidation only for PD-L1 positive tumors (≥1%) on initial biopsy

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