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Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell
R L Ferris1, R Haddad2, C Even3
1Department of Otolaryngology, UPMC Hillman Cancer Center, Pittsburgh, USA.
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 = 240), durvalumab plus tremelimumab (n = 247), or SoC (n = 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72-1.08; P = 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85-1.26; P = 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9-43.1), 30.4% (24.7-36.3), and 30.5% (24.7-36.4) 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.
Trial Registration:
ClinicalTrials.gov: NCT02369874.
Insights
This phase III trial found no significant overall survival benefit for durvalumab or durvalumab plus tremelimumab compared to standard care in recurrent/metastatic head and neck squamous cell carcinoma. However, durvalumab showed some clinical activity with higher survival rates at 12-24 months.
Area of Science:
- Immunotherapy
- Oncology
- Head and Neck Cancer
Background:
- The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis is a target for treating recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC).
- Combining PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors may offer additive benefits.
Purpose of the Study:
- To evaluate the efficacy of durvalumab (anti-PD-L1) or durvalumab plus tremelimumab (anti-CTLA-4) compared to standard of care (SoC) in R/M HNSCC patients.
Main Methods:
- Phase III randomized trial comparing durvalumab, durvalumab plus tremelimumab, or SoC (cetuximab, taxane, methotrexate, or fluoropyrimidine).
- Primary endpoints were overall survival (OS) for each treatment arm versus SoC.
- Secondary endpoints included progression-free survival (PFS) and objective response rate.
Main Results:
- No statistically significant improvement in OS was observed for durvalumab (HR: 0.88) or durvalumab plus tremelimumab (HR: 1.04) versus SoC.
- 12-month survival rates were 37.0% (durvalumab), 30.4% (durvalumab plus tremelimumab), and 30.5% (SoC).
- Treatment-related adverse events were consistent with prior reports, with higher rates of grade ≥3 events in the SoC arm (24.2%) compared to durvalumab (10.1%) and durvalumab plus tremelimumab (16.3%).
Conclusions:
- Durvalumab and durvalumab plus tremelimumab did not demonstrate statistically significant improvements in overall survival compared to standard of care for R/M HNSCC.
- Durvalumab showed clinical activity, evidenced by higher survival rates at 12 to 24 months and response rates.
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