EAGLE: A phase 3, randomized, open-label study of durvalumab (D) with or without tremelimumab (T) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Abstract

6012 Background: EAGLE is a phase 3 study evaluating efficacy of D (anti-PD-L1 mAb) monotherapy and D+T (anti-CTLA-4 mAb) vs standard of care (SOC) in pts with R/M HNSCC who progressed following platinum-based therapy (NCT02369874). Methods: Pts were randomized 1:1:1 to D 10 mg/kg IV every 2 weeks (Q2W), D+T (D 20 mg/kg IV Q4W + T 1 mg/kg IV Q4W for 4 doses, then D 10 mg/kg IV Q2W), or SOC (investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen). The primary endpoint was overall survival (OS) with dual primary objectives of D+T vs SOC and D vs SOC. Additional endpoints included objective response rate (ORR), duration of response (DoR), and adverse events (AEs). Results: 240 pts were randomized to D, 247 to D+T and 249 to SOC. An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favor of the SOC arm (D, PS 0 = 26%, PS 1 = 74%; D+T, PS 0 = 26%, PS 1 = 74%; SOC, PS 0 = 32%, PS 1 = 68%). The risk of death was not statistically significantly different for D compared with SOC (HR: 0.88; 95% CI: 0.72–1.08; P = 0.20) or D+T vs SOC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). Efficacy data are provided in the table. Treatment-related AEs Grade ≥3 were reported in 10.1% of pts (regardless of causality Grade ≥3 AEs were 41.4%) in the D arm, 16.3% (51.2%) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of pts in D, 5% in D+T and 15% in SOC received immunotherapy. Conclusions: D and D+T did not demonstrate a statistically significant improvement in OS compared to standard chemotherapy in pts with R/M HNSCC. Median OS and ORR of D arm were similar to other studies with checkpoint inhibitors. The SOC arm outperformed what has been seen for SOC arms in previous studies; subsequent immunotherapy may have confounded the OS analyses. The safety profile for D and D + T in R/M HNSCC is consistent with previous trials. Clinical trial information: NCT02369874. [Table: see text]

Relationship Between Progression‐Free Survival, Objective Response Rate, and Overall Survival in Clinical Trials of PD‐1/PD‐L1 Immune Checkpoint Blockade: A Meta‐Analysis

“…Overall, 40 trials qualified for the meta‐analysis of PD‐1/PD‐L1 ICB monotherapy for the ITT population ( Table 1 ). 6,7,10,29–66 These included trials of NSCLC ( n = 13), small cell lung cancer ( n = 2), HNSCC ( n = 4), esophageal or gastric or gastroesophageal junction cancer ( n = 6), urothelial bladder cancer ( n = 3), epithelial ovarian cancer ( n = 1), renal cell carcinoma ( n = 2), colorectal cancer ( n = 1), hepatocellular carcinoma ( n = 2), triple negative breast cancer ( n = 1), and melanoma ( n = 5). Among these trials, 13 evaluated pembrolizumab, 14 nivolumab, 7 atezolizumab, 3 durvalumab, and 3 avelumab (as investigational agent).…”

Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

“…EAGLE is a phase III trial comparing durvalumab, durvalumab + tremelimumab, and standard of care in platinum-refractory HNSCC patients. 18 Comparing with SoC, durvalumab alone or durvalumab + tremelimumab did not show significant benefits on OS (Table 3). CHECKMATE 714 (NCT02823574) is a phase II trial comparing nivolumab or nivolumab + ipilimumab in platinum-refractory or platinum-sensitive HNSCC patients.…”

“…The study did not show significant additional benefit with the addition of tremelimumab to durvalumab in low PD‐L1‐ expressing HNSCC. EAGLE is a phase III trial comparing durvalumab, durvalumab + tremelimumab, and standard of care in platinum‐refractory HNSCC patients . Comparing with SoC, durvalumab alone or durvalumab + tremelimumab did not show significant benefits on OS (Table ).…”

Abscopal effect in head and neck cancer: a unicorn summoned once every eon?

“…The trial was also a negative one but it did not make use of SBRT. 21 We do believe that SBRT is an essential component in the context of this discussion, given the low overall response rates (~13-18%) for platinumrefractory recurrent/metastatic head and neck cancer. 22 Another ongoing clinical trial from Bahig et al 23 is using double checkpoint inhibition with durvalumab plus tremelimumab and SBRT (10 Gy x 5) to 2-5 metastatic sites.…”