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Published on: September 25, 2018
Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or
Lillian L Siu1, Caroline Even2, Ricard Mesía3
1Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
Importance:
Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) may overcome immune checkpoint inhibition. It is unknown whether dual blockade can potentiate antitumor activity without compromising safety in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) and low or no PD-L1 tumor cell expression.
Objective:
To assess safety and objective response rate of durvalumab combined with tremelimumab.
Design, Setting, And Participants:
The CONDOR study was a phase 2, randomized, open-label study of Durvalumab, Tremelimumab, and Durvalumab in Combination With Tremelimumab in Patients With R/M HNSCC. Eligibility criteria included PD-L1-low/negative disease that had progressed after 1 platinum-containing regimen in the R/M setting. Patients were randomized (N = 267) from April 15, 2015, to March 16, 2016, at 127 sites in North America, Europe, and Asia Pacific.
Interventions:
Durvalumab (20 mg/kg every 4 weeks) + tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks), or durvalumab (10 mg/kg every 2 weeks) monotherapy, or tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy.
Main Outcomes And Measures:
Safety and tolerability and efficacy measured by objective response rate.
Results:
Among the 267 patients (220 men [82.4%]), median age (range) of patients was 61.0 (23-82) years. Grade 3/4 treatment-related adverse events occurred in 21 patients (15.8%) treated with durvalumab + tremelimumab, 8 (12.3%) treated with durvalumab, and 11 (16.9%) treated with tremelimumab. Grade 3/4 immune-mediated adverse events occurred in 8 patients (6.0%) in the combination arm only. Objective response rate (95% CI) was 7.8% (3.78%-13.79%) in the combination arm (n = 129), 9.2% (3.46%-19.02%) for durvalumab monotherapy (n = 65), and 1.6% (0.04%-8.53%) for tremelimumab monotherapy (n = 63); median overall survival (95% CI) for all patients treated was 7.6 (4.9-10.6), 6.0 (4.0-11.3), and 5.5 (3.9-7.0) months, respectively.
Conclusions And Relevance:
In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way.
Trial Registration:
clinicaltrials.gov Identifier: NCT02319044.
Insights
Dual blockade of programmed death ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) showed manageable safety and clinical benefit in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Further phase 3 study is ongoing.
Area of Science:
- Oncology
- Immunotherapy
- Head and Neck Cancer
Background:
- Dual blockade of PD-L1 and CTLA-4 may overcome immune checkpoint inhibition.
- The efficacy and safety of this dual blockade in patients with R/M HNSCC and low/negative PD-L1 expression are not well-defined.
Purpose of the Study:
- To assess the safety and objective response rate of durvalumab combined with tremelimumab in patients with R/M HNSCC.
- To evaluate durvalumab monotherapy and tremelimumab monotherapy in this patient population.
Main Methods:
- Phase 2, randomized, open-label CONDOR study (N=267) for R/M HNSCC with PD-L1-low/negative disease.
- Patients received durvalumab + tremelimumab, durvalumab monotherapy, or tremelimumab monotherapy.
- Primary endpoints were safety and objective response rate.
Main Results:
- Grade 3/4 treatment-related adverse events occurred in 15.8% (combo), 12.3% (durva), and 16.9% (treme).
- Objective response rates were 7.8% (combo), 9.2% (durva), and 1.6% (treme).
- Median overall survival was 7.6 months (combo), 6.0 months (durva), and 5.5 months (treme).
Conclusions:
- Durvalumab and the combination of durvalumab plus tremelimumab demonstrated manageable toxicity and clinical benefit in R/M HNSCC with low/no PD-L1 expression.
- Minimal difference in efficacy was observed between durvalumab monotherapy and the combination therapy.
- A Phase 3 study is currently underway to further investigate these findings.
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