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 firstand second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab AE 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 þ tremelimumab (12 weeks durvalumab 20 mg/kg þ 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 þ 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), 0.42e0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49e1.04)]. Study B: median OS 11.5 (durvalumab þ tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61e1.05); P ¼ 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59e1.01); P ¼ 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab þ 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 þ tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies. Trial registration: Clinicaltrials.gov identifier: NCT02352948.

Relationship Between Progression‐Free Survival, Objective Response Rate, and Overall Survival in Clinical Trials of PD‐1/PD‐L1 Immune Checkpoint Blockade: A Meta‐Analysis

“…For the end points (patient‐level) analysis, PFS and OS data were extracted from identified trials of durvalumab monotherapy in NSCLC, head and neck squamous cell carcinoma (HNSCC), and bladder cancer. Source studies included the ATLANTIC trial (phase II, greater than or equal to second‐line), 18 ARCTIC (study A; phase III, greater than or equal to third‐line), 19 and study 1108 for NSCLC (phase I/II, greater than or equal to first‐line), 20 CONDOR (phase II, second‐line), 21 and HAWK (phase II, second‐line) 22 for HNSCC, and data from study 1108 for bladder cancer 23 . Similar analyses were used to investigate the correlation between RECIST‐based objective response (i.e., complete or partial response) and OS.…”

CTLA4 has a profound impact on the landscape of tumor-infiltrating lymphocytes with a high prognosis value in clear cell renal cell carcinoma (ccRCC)

“…Recently, the combined inhibition of PD-L1 and CTLA4 has attracted much attention (30). D Planchard et al reported that combination immunotherapy of PD-L1 and CTLA4 considerably prolonged the OS in advanced refractory colorectal cancer (31).…”

Nivolumab monotherapy or combination therapy with Ipilimumab for lung cancer: A meta-analysis of randomized controlled trials

“…Median PFS was 3.9 months (95% CI, 2.8-5.0) with Durvalumab plus Tremelimumab vs 5.4 months (95% CI, 4.6-5.8) with chemotherapy (HR, 1.05; 99.5% CI, 0.72-1.53; P = 0.71). ARCTIC [27] is another clinical trial evaluating the combination of Durvalumab and Tremelimumab compared to SOC chemotherapy. The results of the two studies suggested that Durvalumab alone or in combination with Tremelimumab had clinically signi cant improvement in OS and PFS compared with SOC.…”