2 research outputs found
Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open -label phase III study
Background: Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients.
Patients and methods: Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response. Results: Patients were randomly assigned to receive durvalumab (n 1β4 240), durvalumab plus tremelimumab (n 1β4 247), or SoC (n 1β4 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72e1.08; P 1β4 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85e1.26; P 1β4 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9e43.1), 30.4% (24.7e36.3), and 30.5% (24.7 e36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade !3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively.
Conclusion: There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab
Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study
Head and neck squamous cell carcinoma (HNSCC) is
among the 10 most common cancers worldwide, with
increasing incidence.1 Approximately 10% of patients with
HNSCC will be diagnosed with metastatic disease, and
even when treated early, around half will have disease
recurrence.2,3 The platinum-based doublet chemotherapy
with cetuximab regimen has been the most widely-used
therapy and considered standard of care (SoC) since it
was proven effective in 2007 for recurrent/metastatic
(R/M) HNSCC in the first-line setting.3,4 However, patients
typically progress even after aggressive first-line therapy,
and, until recently, the available options (e.g. cetuximab,
methotrexate, and taxanes) have delivered limited survival
benefits.3
Durvalumab is an immunotherapeutic agent that blocks
the interaction between programmed cell death ligand 1
(PD-L1) and its receptors.5 Durvalumab demonstrated
encouraging response rates and duration of response (DoR)
with a manageable safety profile in patients with HNSCC.6
Although monotherapy agents that block the programmed
cell death protein 1 (PD-1)/PD-L1 axis have shown clinical
activity, immunotherapy combinations have the potential
to improve upon monotherapy activity.7e9 Cytotoxic
T-lymphocyte-associated antigen 4 (CTLA-4) and PD-L1/PD-1
pathways have largely non-redundant roles, suggesting
that blockade of both could have additive or synergistic
effects.10 Indeed, the combination of durvalumab and
tremelimumab, an anti-CTLA-4 monoclonal antibody, was
explored based on improved efficacy over monotherapy in
other solid tumor types.7 This observation, in addition to
the activity demonstrated by durvalumab in earlier R/M
HNSCC studies, served as the rationale to evaluate durvalumab
and tremelimumab in patients with R/M HNSCC.
Several studies, including the EAGLE study, were initiated to
evaluate combination immunotherapy regimens in various
patient groups.11,12 The EAGLE study was the first phase III
study to investigate durvalumab and tremelimumab in patients
with R/M HNSCC who had progressed after platinumbased
therapy.
During the conduct of the EAGLE study, anti-PD-1
monoclonal antibodies were approved for use for R/M
HNSCC progression following a platinum-based regimen.
Treatment with these immunotherapies resulted in a median
overall survival (OS) of 7.5e8.4 months.13,14 These
immunotherapies are now recommended for second-line
treatment as monotherapies for patients with R/M
HNSCC.3,13,14 More recently, immunotherapy alone or in
combination with platinum-based chemotherapy has
shown improvements in OS in the first-line setting,
underscoring the clinical utility of immunotherapy in
HNSCC.15
Here, we report the results of the randomized phase III
EAGLE trial evaluating durvalumab and durvalumab plus
tremelimumab versus SoC therapies in patients with R/M
HNSCC who have progressed following a platinumcontaining
regimen