Durvalumab Does Not Improve OS Versus Standard of Care in First-Line Recurrent or Metastatic HNSCC

February 5, 2021
Hannah Slater

The phase 3 KESTREL trial demonstrated that combination treatment with durvalumab plus tremelimumab did not display an overall survival benefit in “all-comer” patients with metastatic head and neck squamous cell carcinoma versus the EXTREME regimen.

Updated results from the phase 3 KESTREL trial (NCT02551159) indicated that durvalumab (Imfinzi) did not meet the study’s primary end point of improving overall survival (OS) versus a standard of care treatment—chemotherapy plus cetuximab (Erbitux)—in the first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors expressed high levels of PD-L1, according to the agent’s developer, AstraZeneca.

In addition, combination treatment with durvalumab plus tremelimumab did not display an OS benefit in “all-comer” patients, a secondary end point of the study.

“Metastatic head and neck cancer is a complex and challenging disease with a poor prognosis. While we are disappointed by these results, insights from the KESTREL phase 3 trial will advance our understanding and application of immunotherapy across our clinical development program,” Dave Fredrickson, executive vice president of the Oncology Business Unit at AstraZeneca, said in a press release. “We will continue to build on the established benefits of Imfinzi in early lung cancer and small cell lung cancer, to bring immunotherapy treatment options to all patients who may benefit.”

The randomized, open-label, multi-center, global phase 3 KESTREL trial evaluated the use of durvalumab alone or added to the CTLA-4 inhibitor, tremelimumab, versus the EXTREME treatment regimen of cetuximab with cisplatin or carboplatin plus 5-fluorouracil. The trial was conducted in over 200 centers across 23 countries, including centers located in the United States, Europe, South America, and Asia.

The study’s primary end point was OS in patients with high PD-L1 expression in the durvalumab monotherapy arm. Notably, high PD-L1 status was defined by investigators as either 50% or more tumor cells or 25% or more tumor-infiltrating immune cells expressing PD-L1. Moreover, a key secondary end point was OS in “all-comer” patients treated with the combination of durvalumab plus tremelimumab.

Importantly, the safety and tolerability profiles for durvalumab as both a monotherapy and in combination with tremelimumab were found to be consistent with that observed in previous trials. AstraZeneca indicated that the data from this trial will be shared “in due course.”

Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. The agent is approved for the treatment of unresectable, stage III non–small cell lung cancer (NSCLC) following chemoradiation therapy with curative intent in the European Union, United States, Japan, China, and many other countries, based on results observed in the phase 3 PACIFIC trial (NCT02125461). Additionally, durvalumab is approved in the European Union, United States, Japan, and a number of other countries for the treatment of extensive-stage small cell lung cancer (SCLC) based on the phase 3 CASPIAN trial (NCT03043872). Durvalumab is also approved for previously treated patients with advanced bladder cancer in the United States and several other countries.

Currently, as part of a broad clinical program, durvalumab is being tested as a monotherapy and in combination with other anticancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary tract cancer, esophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumors.


Update on KESTREL Phase III trial of Imfinzi with or without tremelimumab in the 1st-line treatment of recurrent or metastatic head and neck cancer. News release. AstraZeneca. Published February 5, 2021. Accessed February 5, 2021. https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2021/update-on-kestrel-phase-iii-trial-for-imfinzi.html