Durvalumab Shows Similar Outcomes Across NSCLC PD-L1 Expression Groups

Durvalumab (Imfinzi) after chemoradiotherapy (CRT) produced similar overall survival (OS) and cancer-related survival outcomes among patients with stage III non–small cell lung cancer (NSCLC) who had PD-L1–positive or PD-L1–negative tumors, according to a poster presentation on real-world findings from Veterans Health Administration (VMA) facilities at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

In a multivariate analysis of patients with PD-L1 positivity or negativity that accounted for an ECOG performance status of 1 or higher, OS outcomes were comparable between groups (HR, 0.93; 95% CI, 0.70-1.24). The median OS was 33.3 months (95% CI, 29.8-47.3) in the PD-L1–positive population and 28.5 months (95% CI, 21.6-39.7) in the PD-L1–negative population.

Cancer-related OS outcomes were similar regardless of whether patients had PD-L1–positive or PD-L1–negative tumors (HR, 0.87; 95% CI, 0.63-1.21). The median cancer-related OS was 20.4 months (95% CI, 16.0-25.4) for those with PD-L1–positive disease and 20.6 months (95% CI, 15.4-28.5) for those with PD-L1–negative status.

The most common causes of death in the PD-L1–positive population (n = 221) and PD-L1–negative group (n = 119), respectively, included disease progression (84% vs 77%; P = .19), infection or sepsis (19% vs 6%; P = .01), and cardiac events (14% vs 14%; P = 1.00).

“In this real-world study of a patient population with stage III unresectable NSCLC from [the VHA] system, who were older and with worse performance status than those in the PACIFIC clinical trial [NCT02125461], treatment with durvalumab post-CRT resulted in similar OS and cancer-related OS for those with PD-L1 negative and positive tumors,” Zohra Nooruddin, MD, a hematology/oncology/bone marrow transplant physician and associate professor at UT Health San Antonio, wrote with coauthors in the poster.¹

According to the trial investigators, consolidative durvalumab had previously demonstrated the ability to improve OS and progression-free survival for patients with stage III unresectable NSCLC after CRT, although it was uncertain whether greater benefits occurred for patients with PD-L1 positivity or negativity.² Although previous data showed no difference in OS outcomes across these PD-L1 expression groups, the authors stated that no other study has compared cancer-related OS in these populations.³

Investigators of this real-world study assessed patients with stage III unresectable NSCLC who received durvalumab after CRT at any VHA facility from January 2017 up to June 2020. The study included a retrospective collection of electronic health record data on durvalumab treatment courses, OS, and cancer-related OS, which were derived from each patient’s chart and death certificate. Investigators employed Kaplan-Meier and Cox regression models to evaluate cancer-related OS outcomes.

The median age was 69 years (IQR, 64-73) in the PD-L1–positive population and 69 years (IQR, 64-72) in the PD-L1–negative group (P = .41), and most were male (94% vs 94%; P = 1.00) and White (77% vs 76%; P = .72). Additionally, most patients in each respective group had an ECOG performance status of 1 or higher (74% vs 85%; P = .05), squamous histology (53% vs 45%; P = .18), and stage IIIA disease (58% vs 50%; P = .17). In each population, 5% and 4% of patients had EGFR mutations (P = 1.00), and 2% and 9% had RAS-mutated disease (P = .10).

The median number of durvalumab doses was 15 (IQR, 6-24) in the PD-L1–positive group and 13 (IQR, 5-24) in the PD-L1–negative population (P = .55). The median follow-up was 33 months (IQR, 12-69) and 28 months (IQR, 11-63) in each group (P = .22).

According to the investigators, the study’s retrospective observational design may have introduced some unaccounted confounding factors despite adjustment. Other potential limitations included missing PD-L1 data for more than half of the original cohort as well as the predominantly older, male, and White population from the VHA system, which may limit the study’s generalizability to broader patient populations.

References

1. Nooruddin Z, Gilmore C, Moore A, et al. Cancer-related overall survival for patients on durvalumab for stage III unresectable non–small cell lung cancer with PD-L1 positive and negative tumors. J Clin Oncol. 2026;44(suppl 16):8026. doi:10.1200/JCO.2026.44.16_suppl.8026
2. Spigel DR, Faivre-Finn C, Gray JE, et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol. 2022;40(12):1301-1311. doi:10.1200/JCO.21.01308. Erratum in: J Clin Oncol. 2022;40(17):1965. doi:10.1200/JCO.22.01023.
3. Burton EM, Moore A, Nooruddin Z, et al. Durvalumab outcomes for patients with PD-L1 positive and negative stage III unresectable non-small cell lung cancer treated at veterans health administration facilities. doi:10.1200/JCO.2023.41.16_suppl.e18793