Squamous cell carcinoma of the head and neck: JAVELIN Head and Neck 100 discontinued due to efficacy doubts
An update from the phase III JAVELIN Head and Neck 100 study evaluating Avelumab ( Bavencio ) in addition to chemoradiotherapy ( CRT ) versus standard-of-care CRT in patients with untreated locally advanced squamous cell carcinoma of the head and neck ( LA SCCHN ), was announced.
The independent Data Monitoring Committee ( DMC ) has recommended to terminate the JAVELIN Head and Neck 100 trial, as the study is unlikely to show a statistically significant improvement in the primary endpoint of progression-free survival ( PFS ) based on a preplanned interim analysis.
There has been limited innovation for patients with locally advanced SCCHN over the past 10 years.
Despite aggressive standard-of-care treatment with high-dose chemotherapy combined with radiotherapy, LA SCCHN will ultimately recur in a large proportion of patients.
In recognition of the unmet need for additional treatment options that can prevent recurrence or metastatic disease, the JAVELIN Head and Neck 100 trial was initiated.
JAVELIN Head and Neck 100 is the first phase III study to report topline results for an immune checkpoint inhibitor in combination with chemoradiotherapy in LA SCCHN.
JAVELIN Head and Neck 100 is a randomized, double-blind, placebo-controlled, parallel-arm study investigating treatment with avelumab plus standard-of-care chemoradiotherapy followed by Avelumab maintenance versus chemoradiotherapy alone in patients with previously untreated LA SCCHN.
A total of 697 patients who had not received prior therapy for locally advanced SCCHN and were eligible for chemoradiotherapy with curative intent were randomly assigned to receive Avelumab plus CRT or CRT alone.
The primary endpoint was progressione-free survival per modified RECIST criteria ( version 1.1 ). Secondary endpoints included overall survival ( OS ), time to locoregional failure, time to distant metastatic failure, overall response, duration of response and pathologic complete response.
Head and neck cancer is the sixth most common cancer worldwide. In 2016, there were nearly 150,000 newly diagnosed cases in the United States, Japan and Europe.
Approximately 60% of people are diagnosed with head and neck cancer when their disease has already progressed to the locally advanced stage ( stage III-IVB ). At this stage, the cancer has spread from its site of origin to local lymph nodes, but not another part of the body. Standard of care for these patients includes high-dose chemotherapy combined with radiotherapy.
Avelumab is a human anti-programmed death ligand-1 ( PD-L1 ) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, Avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.( Xagena )
Source: EMD Serono & Pfizer, 2020