The phase III JAVELIN Head and Neck 100 trial has been terminated after an interim analysis showed that the addition of avelumab to standard-of-care chemoradiotherapy was unlikely to lead to a statistically significant improvement in progression-free survival in patients with untreated locally advanced squamous cell carcinoma of the head and neck.
The phase III JAVELIN Head and Neck 100 trial has been terminated after an interim analysis showed that the addition of avelumab (Bavencio) to standard-of-care chemoradiotherapy (CRT) was unlikely to lead to a statistically significant improvement in progression-free survival (PFS) in patients with untreated locally advanced squamous cell carcinoma of the head and neck (SCCHN).1
The findings came from a preplanned interim analysis by an independent Data Monitoring Committee (DMC), which determined that the trial was unlikely to meet the primary endpoint of PFS. The actual data from the study will be shared with the oncology community at a future time, Pfizer, the manufacturer of avelumab, reported in a press release.
The double-blind phase III JAVELIN Head and Neck 100 trial (NCT02952586) included 697 treatment-naive patients with locally advanced SCCHN. Patients were randomized to either avelumab plus standard-of-care CRT followed by avelumab maintenance, or CRT alone. Beyond the primary PFS endpoint, secondary endpoints included overall survival, time to locoregional failure, time to distant metastatic failure, overall response, duration of response, and pathologic complete response.
Other checkpoint inhibitors have had success in head and neck cancer. For example, in June 2019, the FDA approved pembrolizumab (Keytruda) for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma, as monotherapy in patients whose tumors express PD-L1 (composite positive score [CPS] ≥1) or in combination with platinum and fluorouracil (FU) for this patient population, irrespective of PD-L1 expression.
The approval was based on the phase III KEYNOTE-048 trial, in which single-agent pembrolizumab led to a 22% reduction in the risk of disease progression or death compared with the standard EXTREME regimen, which comprises cetuximab (Erbitux) with carboplatin or cisplatin plus FU, in patients with PD-L1—positive tumors (HR, 0.78; 95% CI, 0.64-0.96; P = .0171).2 When in combination with chemotherapy in the overall KEYNOTE-048 population, the PD-1 inhibitor led to a 23% reduction in the risk of disease progression or death (HR, 0.77; 95% CI, 0.63-0.93; P = .0067).
Pembrolizumab is also approved as a single agent for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Additionally, Nivolumab (Opdivo) is approved by the FDA for patients with metastatic or recurrent SCCHN following progression on platinum-based therapy. The FDA based its approval on data from the CheckMate-141 study showing that the median overall survival with nivolumab was 7.5 months compared with 5.1 months with investigator's choice (HR, 0.70; 95% CI, 0.52-0.92; P = .0101).3 The objective response rate was 13.3% with nivolumab and 5.8% for investigator's choice.