De-escalating adjuvant durvalumab treatment duration in stage III non-small cell lung cancer. (August 2022)

• Record Type: Journal Article
• Authors: Bryant, Alex K.; Sankar, Kamya; Zhao, Lili; Strohbehn, Garth W.; Elliott, David; Moghanaki, Drew; Kelley, Michael J.; Ramnath, Nithya; Green, Michael D.
• Is Part Of: European journal of cancer. Volume 171(2022)
• Page Start: 55
• Page End: 63
• Publication Date: 2022-08
• Subjects: Non-small cell lung cancer -- Immunotherapy -- Durvalumab -- De-escalation -- Marginal structural modelling -- Treatment duration; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2022.04.033
• Languages: English
• ISSNs: 0959-8049

Abstract

Abstract: Background: One year of adjuvant durvalumab following concurrent chemoradiotherapy significantly improves progression-free survival (PFS) and overall survival (OS) for patients with stage III non-small cell lung cancer (NSCLC). However, the optimal length of adjuvant therapy has not been determined. Methods: We identified patients with stage III NSCLC treated with definitive chemoradiation and adjuvant durvalumab from November 2017 to April 2021 from the United States Veterans Affairs system. Predictors of early durvalumab discontinuation were evaluated with Cox proportional hazards regression. The effect of differing durations of durvalumab treatment (up to 6, 9, and 12 months) on PFS and OS were compared with a marginal structural model and time-dependent Cox modelling. Results: We included 1006 patients with stage III non-small cell lung cancer who received concurrent chemoradiotherapy and at least one dose of adjuvant durvalumab. The median duration of durvalumab treatment was 7 months (interquartile range 2.8–11.5) and 31% completed the intended durvalumab course. The most common reasons for early discontinuation were tumour progression (22%), immune-related adverse events (15%), and non-immune-related toxicity (6.0%), Marginal structural models suggested similar PFS for 9 months versus 12 months of durvalumab treatment and inferior PFS for 6 months versus 12 months. Conclusions: A substantial proportion of patients undergoing adjuvant durvalumab discontinue therapy early due to toxicity, and shorter durvalumab treatment durations may provide similar disease control to 12 months of therapy. Prospective randomised controlled studies are needed to characterise the optimal durvalumab treatment duration in locally advanced NSCLC patients. Highlights: Real-world patients have higher durvalumab toxicity than in clinical trials. Real-world patients receive fewer durvalumab cycles than in clinical trials. Shorter adjuvant durvalumab durations may be equivalent to the current standard. Shorter durvalumab durations may decrease cost and improve toxicity. Prospective study of shorter durvalumab durations is warranted.