KESTREL
Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck
Phase 3NCT02551159
- Population
- Recurrent or metastatic head and neck squamous cell carcinoma, no prior systemic treatment for recurrent or metastatic disease
- Design
- Randomised (2:1:1), open-label phase 3 study in patients with head and neck squamous cell carcinoma who had not received prior systemic treatment for recurrent or metastatic disease. Arms: durvalumab (anti-PD-L1) plus tremelimumab (anti-CTLA-4), durvalumab alone, or the EXTREME regimen (platinum, 5-fluorouracil and cetuximab) until progression. The abstract reports efficacy of durvalumab with or without tremelimumab versus EXTREME in patients with PD-L1-high tumours and in all randomised patients; it does not state the primary endpoints.
- Arms
- Durvalumab plus tremelimumab (experimental): Durvalumab 1500 mg every 4 weeks plus tremelimumab 75 mg every 4 weeks (up to four doses), until progression
- Durvalumab alone (experimental): Durvalumab 1500 mg every 4 weeks until progression
- EXTREME regimen (control): Platinum, 5-fluorouracil and cetuximab until progression
- People
- Psyrri A, KESTREL Investigators
OSHR 0.96 (95% CI 0.69–1.32)Δ median OS0 monthsOSHR 1.05 (95% CI 0.80–1.39)Δ median OS+0.3 monthsΔ median PFS−2.6 monthsΔ DOR+39.5 points
Show the numbers
| Endpoint | Analysis | Durvalumab plus tremelimumab / Durvalumab alone | EXTREME regimen | Effect |
|---|---|---|---|---|
| OSPD-L1-high expression (the abstract does not give the PD-L1 cut-off) | primaryPsyrri 2023 | median 10.9 months | median 10.9 months | HR 0.96 (95% CI 0.69–1.32)P=0.787Abstract: durvalumab was not superior to EXTREME for overall survival in this population. This comparison is the registered primary outcome on ClinicalTrials.gov NCT02551159 (OS, durvalumab versus standard of care, PD-L1 TC/IC high subgroup). |
| OSPD-L1-high expression (the abstract does not give the PD-L1 cut-off) | finalPsyrri 2023 | median 11.2 months | median 10.9 months | HR 1.05 (95% CI 0.80–1.39)Abstract: durvalumab plus tremelimumab was not superior to EXTREME for overall survival in this population. No P value is stated in the abstract. ClinicalTrials.gov lists this comparison as a secondary outcome; the abstract does not label the analysis, and the one reported analysis is shown as final. |
| PFSNot specified in the abstract sentence (it follows the PD-L1-high overall survival analysis) | finalPsyrri 2023 | median 2.8 months | median 5.4 months | Medians only; the abstract gives no hazard ratio for progression-free survival. Registered as a secondary outcome on ClinicalTrials.gov; the abstract does not label the analysis. |
| DORNot specified in the abstract sentence | finalPsyrri 2023 | 49.3% | 9.8% | Percentage of patients remaining in response at 12 months, as the abstract states; the denominator (responders) is not given in the abstract. Registered as a secondary outcome on ClinicalTrials.gov; the abstract does not label the analysis. |
| Endpoint | Analysis | Durvalumab plus tremelimumab / Durvalumab alone | EXTREME regimen | Effect |
|---|---|---|---|---|
| OSPD-L1-high expression (the abstract does not give the PD-L1 cut-off) | primaryPsyrri 2023 | median 10.9 months | median 10.9 months | HR 0.96 (95% CI 0.69–1.32)P=0.787Abstract: durvalumab was not superior to EXTREME for overall survival in this population. This comparison is the registered primary outcome on ClinicalTrials.gov NCT02551159 (OS, durvalumab versus standard of care, PD-L1 TC/IC high subgroup). |
| OSPD-L1-high expression (the abstract does not give the PD-L1 cut-off) | finalPsyrri 2023 | median 11.2 months | median 10.9 months | HR 1.05 (95% CI 0.80–1.39)Abstract: durvalumab plus tremelimumab was not superior to EXTREME for overall survival in this population. No P value is stated in the abstract. ClinicalTrials.gov lists this comparison as a secondary outcome; the abstract does not label the analysis, and the one reported analysis is shown as final. |
| PFSNot specified in the abstract sentence (it follows the PD-L1-high overall survival analysis) | finalPsyrri 2023 | median 2.8 months | median 5.4 months | Medians only; the abstract gives no hazard ratio for progression-free survival. Registered as a secondary outcome on ClinicalTrials.gov; the abstract does not label the analysis. |
| DORNot specified in the abstract sentence | finalPsyrri 2023 | 49.3% | 9.8% | Percentage of patients remaining in response at 12 months, as the abstract states; the denominator (responders) is not given in the abstract. Registered as a secondary outcome on ClinicalTrials.gov; the abstract does not label the analysis. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.96 | 0.69–1.32 |
| OS | 1.05 | 0.8–1.39 |
- Durvalumab alone (experimental)
- EXTREME regimen (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab alone | EXTREME regimen |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 64.1% | 64.1% |
| 14 | 41.1% | 41.1% |
| 20 | 28.0% | 28.0% |
| 27 | 18.0% | 18.0% |
- Durvalumab plus tremelimumab (experimental)
- EXTREME regimen (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Durvalumab plus tremelimumab | EXTREME regimen |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 7 | 64.8% | 64.1% |
| 14 | 42.0% | 41.1% |
| 21 | 27.3% | 26.3% |
| 28 | 17.7% | 16.9% |
Appears in
Sources
Psyrri A, Fayette J, Harrington K, Gillison M, Ahn MJ, Takahashi S, et al. Durvalumab with or without tremelimumab versus the EXTREME regimen as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck: KESTREL, a randomized, open-label, phase III study. Ann Oncol. 2023;34(3):262-274.