Ibrutinib did not meet the primary efficacy endpoint in patients with R/R FL in the phase II DAWN study

On 31^st May 2018, results from the phase II DAWN study were published in the Journal of Clinical Oncology by Ajay K. Gopal, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues. The study evaluated the efficacy and safety of ibrutinib in patients with relapsed/refractory (R/R) follicular lymphoma (FL).

Study Overview

• N = 110 patients with R/R FL were included in the study. 67% of patients were male and the median age was 61.5 years (range, 28–87). Patients had a median of 3 prior lines of therapy
• Patients were treated with ibrutinib 560 mg daily until disease progression or unacceptable toxicity
• The primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC)
• Secondary endpoints included; duration of response (DOR), progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS)

Key Findings

• Median follow-up was 27.7 months
• ORR = 20.9% (95% CI, 13.7–29.7%)
  • N = 12 patients had a complete response (CR) 11% (95% CI, 5.8–18.3%)
  • The study, therefore, did not meet its primary objective, defined as an ORR with the lower bound threshold of >18%
• Median DOR = 19.4 months
• Median PFS = 4.6 months (95% CI, 2.8–5.5)
• Median TTNT = 16 months (95% CI, 10.7–19.1)
• 30-month OS = 61% (95% CI, 0.51–0.70%)
• Most frequent adverse events (AEs) grade ≥3 included; neutropenia (n = 15), anemia (n = 10) and fatigue (n = 6)
  • N = 8 deaths were reported during the study. 2 fatal AE cases were considered possibly related to ibrutinib (neutropenic sepsis and pneumonia)

The authors concluded that since the study did not meet its primary endpoint, ibrutinib monotherapy cannot be supported in patients with R/R FL.