Outcomes With Durvalumab after Chemoradiotherapy in Stage IIIA-N2 Non-small-cell Lung Cancer: an Exploratory Analysis from the PACIFIC Trial

Background: The phase III PACIFIC trial (NCT02125461) established consolidation durvalumab as standard of care for patients with unresectable, stage III non-small-cell lung cancer (NSCLC) and no disease progression following chemoradiotherapy (CRT). In some cases, patients with stage IIIA-N2 NSCLC are considered operable, but the relative benefit of surgery is unclear. We report a post-hoc, exploratory analysis of clinical outcomes in the PACIFIC trial, in patients with or without stage IIIA-N2 NSCLC.
Methods: Patients with unresectable, stage III NSCLC and no disease progression after ≥2cycles of platinum-based, concurrent CRT were randomized 2:1 to receive durvalumab (10 mg/kg intravenously every 2 weeks for 12 months) or placebo, 1–42 days after CRT. The primary endpoints were progression-free survival (PFS; assessed by blinded independent central review according to RECIST version 1.1) and overall survival (OS). Treatment effects within subgroups were estimated by hazard ratios (HRs) from unstratified Cox-proportionalhazards models.
Results: Of 713 randomized patients, 287 (40%) had stage IIIA-N2 disease. Baseline characteristics were similar between patients with or without stage IIIA-N2 NSCLC. With a median follow-up of 14.5 months (range 0.2–29.9 months), PFS was improved with durvalumab versus placebo in both patients with [HR = 0.46; 95% confidence interval (CI), 0.33–0.65] or without (HR = 0.62; 95% CI, 0.48–0.80) stage IIIA-N2 disease. Similarly, with a median follow-up of 25.2 months (range 0.2–43.1 months), OS was improved with durvalumab versus placebo in patients with (HR = 0.56; 95% CI, 0.39–0.79) or without (HR = 0.78; 95% CI, 0.57–1.06) stage IIIA-N2 disease. Durvalumab had a manageable safety profile irrespective of stage IIIA-N2 status.
Conclusions: Consistent with the intent-to-treat population, treatment benefits with durvalumab were confirmed in patients with stage IIIA-N2 unresectable NSCLC. Prospective studies are needed to determine the optimal treatment approach for patients who are deemed operable.