AstraZeneca has reported that the phase III EAGLE trial has missed its primary endpoint, as patients with recurrent or metastatic head and neck squamous cell carcinoma who progressed after platinum-based chemotherapy did not see a survival benefit with durvalumab alone or combined with tremelimumab.
Sean Bohen, MD, PhD
AstraZeneca (MedImmune) has reported that the phase III EAGLE trial has missed its primary endpoint, as patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who progressed after platinum-based chemotherapy did not see a survival benefit with durvalumab (Imfinzi) alone or combined with tremelimumab.
Although the company did not report any specific data from the study, they said there were no new safety signals with durvalumab monotherapy or the combination of the 2 immune checkpoint inhibitors. Specific study results are expected to be reported at an upcoming medical conference.
“The prognosis for recurrent or metastatic head and neck squamous cell cancer is very poor and new treatments for this group of cancers are urgently needed. While these results are disappointing, we remain committed to evaluating the potential of Imfinzi and other innovative medicines for patients with head and neck cancer,” Sean Bohen, MD, PhD, executive vice president, Global Medicines Development and chief medical officer at AstraZeneca, said in a statement.
“We look forward to seeing the results of the phase III KESTREL trial of Imfinzi and tremelimumab in patients who have not received prior chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma in the first half of 2019,” added Bohen.
The global, multicenter, open-label phase III EAGLE trial randomized patients to single-agent durvalumab, durvalumab plus tremelimumab, or standard chemotherapy in patients with recurrent/metastatic HNSCC who progressed following platinum-based chemotherapy. The population was all-comer, regardless of PD-L1 status. Beyond the primary OS endpoint, secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response.
Previously reported data from the single-arm phase II HAWK study had shown promising single-agent activity for durvalumab in HNSCC. The study included 112 patients with recurrent/metastatic HNSCC who had not received prior immunotherapy and who had a PD-L1 expression level on tumor cells of ≥25%. Patients had progression or recurrence during or following 1 platinum-based regimen.
The median patient age was 60 years, 71.4% were male, 61.6% were current or former smokers, and 34.3% were HPV-positive. Patients received durvalumab at 10 mg/kg IV for up to 12 months or until disease progression, unacceptable toxicity, or start of another anticancer treatment. ORR was the primary endpoint, with OS and PFS as secondary endpoints.
The median duration of treatment was 3.45 months and the median follow-up was 6.13 months at the data cutoff date of March 31, 2017. The ORR among 111 evaluable patients was 16.2 % (n = 18; 95% CI, 9.9-24.4). Ten of the responses were ongoing at the cutoff. The disease control rate at 24 weeks was 23.4%. An exploratory analysis showed that the ORR rates among HPV-positive and HPV-negative patients were 29.4% versus 10.8%, respectively.
The median PFS was 2.1 months (95% CI, 1.9-3.7) and the median OS was 7.1 months (95% CI, 4.9-9.9). At 12 months, the OS rate was 33.6% (95% CI, 24.8-42.7).
The rate of grade ≥3 treatment-related adverse events (TRAEs) was 8%. There was only 1 patient discontinuation due to a TRAE and no deaths associated with a TRAE.
Durvalumab has FDA-approved indications for nonsmall cell lung cancer and urothelial carcinoma.
Zandberg D, Algazi A, Good JS, et al. Durvalumab for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): preliminary results from a single-arm, phase 2 study. In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract 1042O