Durvalumab After Chemoradiotherapy in Patients With Unresectable Stage III Non–Small Cell Lung Cancer

Importance The PACIFIC trial established consolidation durvalumab as the standard of care following chemoradiotherapy (CRT) for patients with unresectable stage III non–small cell lung cancer (NSCLC). Understanding its benefit in routine US clinical practice is critical. Objective To report characteristics, treatment patterns, and outcomes of patients who did or did not receive durvalumab. Design, Setting, and Participants Two prespecified cohorts were curated in this retrospective cohort study (SPOTLIGHT). Deidentified patient-level data from a US database (Flatiron Health) were analyzed. Patients had unresectable stage III NSCLC, were diagnosed on or after January 1, 2011, had 2 or more visits on or afterward, and received CRT. Data were analyzed from May 2021 to October 2023. Exposures Patients started durvalumab after CRT (durvalumab cohort) or ended CRT without durvalumab (nondurvalumab cohort) by June 30, 2019, to allow 15 or more months of follow-up from CRT end. Main Outcomes and Measures End points included progression-free survival (PFS), overall survival (OS), time to first subsequent therapy or death (TFST), and time to distant metastasis or death (TTDM). Results The durvalumab cohort included 332 patients (median IQR age, 67.5 60.8-74.0 years; 187 were male 56.3%, 27 were Black 8.7%, 33 were other races 10.7%, and 249 were White 80.6%) and the nondurvalumab cohort included 137 patients (median (IQR) age, 70.0 64.0-75.0 years; 89 65.0% were male, 11 8.9% were Black, 19 15.4% were other races, and 93 75.6% were White). Most patients had a smoking history (durvalumab, 316 patients 95.2% and nondurvalumab, 132 patients 96.4%) and Eastern Cooperative Oncology Group performance status 0 through 1 (durvalumab, 251 patients 90.9% and nondurvalumab, 88 patients 81.5%). Median (IQR) CRT duration was 1.6 (1.4-1.8) months for the durvalumab cohort and 1.5 (1.4-1.8) months for the nondurvalumab cohort. Median time to durvalumab discontinuation was 9.5 months (95% CI, 7.8-10.6 months). Median TFST and TTDM were not reached (NR) in the durvalumab cohort and 8.3 months (95% CI, 4.8-11.8 months) and 11.3 months (95% CI, 6.4-14.5 months), respectively, in the nondurvalumab cohort. Median PFS and OS were 17.5 months (95% CI, 13.6-24.8 months) and NR in the durvalumab cohort and 7.6 months (95% CI, 5.2-9.8 months) and 19.4 months (95% CI, 11.7-24.0 months) in the nondurvalumab cohort. In Cox regression analyses of patients who completed concurrent CRT without progression, durvalumab was associated with a lower risk of progression or death (hazard ratio HR, 0.36; 95% CI, 0.26-0.51) and lower risk of death (HR, 0.27; 95% CI, 0.16-0.43), adjusted for prior platinum agent and patient characteristics. Conclusions and Relevance In this cohort study, findings were consistent with PACIFIC, and durvalumab was associated with a lower risk of progression and/or death. Further investigation is warranted to explain why patients did not receive durvalumab after its approval.