ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment for metastatic non-small cell lung cancer

Abstract Background Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥third-line treatment for mNSCLC. Patients and methods ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing PD-L1 were randomized (1:1) to durvalumab (up to 12 months 10 mg/kg q2w) or SoC. Study B: 469 patients with PD-L1 TC Results Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months (HR 0.63 [95% CI, 0.42–0.93]); median PFS 3.8 (durvalumab) versus 2.2 (SoC) months (HR 0.71 [95% CI, 0.49–1.04]). Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months (HR 0.80 [95% CI, 0.61–1.05]; P=0.109). Median PFS of 3.5 months for both groups (HR 0.77 [95% CI, 0.59–1.01]; P=0.056). Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; Study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; Study B). Conclusions In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC