Real-world survival outcomes, treatment patterns, and impact of PD-L1 expression among patients with unresectable, stage III NSCLC treated with CRT → durvalumab in Canada: The RELEVANCE study

Abstract

Background: Chemoradiotherapy (CRT) followed by durvalumab (CRT → durvalumab) is standard of care to treat patients with unresectable, stage III non-small cell lung cancer (NSCLC). The RELEVANCE study was designed to provide real-world effectiveness and safety data for CRT → durvalumab in Canadian settings.

Patients and methods: RELEVANCE was a retrospective, observational, multicenter chart review that included adult patients with unresectable, stage III NSCLC treated with CRT alone or CRT → durvalumab at 5 Canadian cancer centers. Key outcomes included treatment patterns, adverse events of special interest (AESI), and overall survival (OS).

Results: 487 patients were included (144 CRT alone; 343 CRT → durvalumab). Median follow-up was 43.1 and 35.8 months for the CRT alone and CRT → durvalumab groups, respectively. The most frequently observed regimen included radiotherapy dose 54-66 Gy and radiosensitizing carboplatin. Median treatment duration was 1.5 months (CRT alone) and 13.4 months (CRT → durvalumab), and 47 % of patients completed a full course of durvalumab. Median OS and 3-year OS rate were 21.3 months and 32 % for CRT alone and 44.6 months and 56 % for CRT → durvalumab. Exploratory analysis by programmed cell death-ligand 1 (PD-L1) expression status of the CRT → durvalumab group noted 3-year OS rates of 69 %, 44 %, and 39 % in the PD-L1 ≥ 50 % (high), 1 %-49 % (intermediate), and < 1 % (negative) populations, respectively (32 %, 38 %, and 24 % for CRT alone, respectively). PD-L1 high expression was associated with lower risk of death vs. PD-L1 negative expression (P < 0.05). The most common AESI with CRT → durvalumab was pneumonitis. Median OS for patients who completed durvalumab was not reached and was 41.3 months among patients who discontinued durvalumab due to AEs.

Conclusion: Results validate the treatment benefit and safety of the PACIFIC regimen in real-world Canadian settings. Among patients who received CRT → durvalumab, there was a correlation between increasing PD-L1 status and improved OS; however, shorter OS was observed in patients discontinuing durvalumab early due to AEs.

Twitter abstract: Real-world Canadian RELEVANCE study validates effectiveness and safety of durvalumab in patients with unresectable, stage III NSCLC.

Keywords: Chemoradiotherapy; Durvalumab; Non-small cell lung cancer; Overall survival; Programmed cell death-ligand 1; Progression-free survival; Real world.