ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of 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 of mNSCLC.

Patients and methods: ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B).

Results: Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (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 <25%). Safety profiles were consistent with previous studies.

Trial registration: Clinicaltrials.gov identifier: NCT02352948.

Keywords: ARCTIC; durvalumab; immunotherapy; metastatic non-small-cell lung cancer; tremelimumab.

Conflict of interest statement

Disclosure DP has served in an advisory role and provided consultancy or lectures for AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche, has received honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche, has undertaken clinical trials research for AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo, and has received travel/accommodation/expenses from AstraZeneca, Roche, Novartis, prIME Oncology, and Pfizer. NR reports personal fees and non-financial support from AstraZeneca, Boehringer-Ingelheim, Hoffmann La-Roche, Bristol-Myers Squibb, and Pfizer, personal fees from MSD Sharp & Dohme and Takeda, and non-financial support from AbbVie, all outside the submitted work. SS has received lecture fees and research grants from AstraZeneca. DM-M has served as a speaker and advisory board member for Roche, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, and Pierre-Fabre. SN reports speakers’ bureau/advisory work for Eli Lilly, Roche, Bristol-Myers Squibb, Takeda, Boehringer-Ingelheim, AstraZeneca, MSD, Pfizer, Bayer, and AbbVie. YT has received research funding from Taiho, Boehringer-Ingelheim, Chugai, and Kyowa Hakko Kirin. RS has served as an advisory board member for AstraZeneca, Bristol-Myers Squibb, Boehringer-Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, and Yuhan, and has received research grants from AstraZeneca and Boehringer-Ingelheim. SLG has received non-financial support from Boehringer-Ingelheim, AstraZeneca, Sanofi-Aventis, and Novartis, and research grants from Boehringer-Ingelheim, AstraZeneca, and Novartis. RM, US, and PS are full-time employees of AstraZeneca. MP was a contractor for AstraZeneca at the time of the study. All remaining authors have declared no conflicts of interest.

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