February 5, 2021 - Durvalumab failed to improve overall survival over the EXTREME chemotherapy regimen in the frontline treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with tumors expressed high levels of PD-L1, missing a primary end point of the phase 3 KESTREL trial.
Durvalumab (Imfinzi) failed to improve overall survival (OS) over the EXTREME chemotherapy regimen comprised of 5-fluorouracil (5-FU), platinum-based chemotherapy, and cetuximab (Erbitux) in the frontline treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with tumors expressed high levels of PD-L1, missing a primary end point of the phase 3 KESTREL trial (NCT02551159).1
Moreover, the combination of durvalumab and tremelimumab also failed to demonstrate an OS benefit in all-comer patients. The safety of durvalumab as a single agent, and in combination with tremelimumab, proved to be consistent with previous data.
“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, stated in a press release.
In the open-label, multicenter, global, phase 3 trial, investigators set out to evaluate durvalumab or durvalumab plus tremelimumab versus the EXTREME regimen comprised of cetuximab and 5-FU with cisplatin or carboplatin in the first-line treatment with recurrent or metastatic HNSCC.
To be eligible for enrollment, patients had to be at least 18 years of age, evidence of recurrent or metastatic HNSCC, and an ECOG performance status of 0-1.2 Patients could not have previously received systemic chemotherapy for recurrent or metastatic disease and could not have previously exposed to immune-mediated therapy.
If they had histologically and cytologically confirmed disease, tumor progression or recurrence within 6 months of the last dose of platinum therapy in the primary treatment setting, or if they received radiotherapy or hormonal therapy for treatment within 30 days before the first dose of study treatment, they could not participate. Patients could also not have active or previous autoimmune or inflammatory disorders.
For the trial, patients were randomized 2:1:1 receive either durvalumab plus tremelimumab, durvalumab monotherapy, or standard of care. Treatment was continued until disease progression. Investigators assessed tumors via computed tomography scans or magnetic resonance imaging scans. They evaluated for efficacy via objective tumor assessments every 6 weeks for the first 24 weeks of treatment, followed by every 8 weeks thereafter, until treatment discontinuation. Patients were followed every 3 months for survival after confirmed progressive disease.
The primary end point of the trial was OS in patients with high PD-L1 expression in the single-agent durvalumab treatment arm. A key secondary end point of the trial was OS in all-comer patients who received durvalumab plus tremelimumab.
“We will continue to build on the established benefits of [durvalumab] in early lung cancer and small cell lung cancer, to bring immunotherapy treatment options to all patients who may benefit,” added Fredrickson.