Study lead Jean-Pascal Machiels, Cliniques Universitaires Saint-Luc (UCLouvain) and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Brussels, Belgium said: “The efficacy of pembrolizumab with or without chemotherapy is well-established in patients with recurrent or metastatic head and neck squamous cell carcinoma, and there was a strong rationale to study pembrolizumab in patients with locally advanced disease. Although pembrolizumab combined with concurrent chemoradiation therapy and as maintenance therapy did not reach statistical significance, it’s suggestive that the addition of pembrolizumab had a clinically meaningful effect on event-free survival, with a 24-month EFS rate of 63.2% for the combination compared to 56.2% for chemoradiation alone. In addition, our data support the hypothesis that PD-L1 expression measured by CPS may be an informative predictive biomarker to better tailor the population that could benefit from pembrolizumab in this setting”
“The data presented from the KEYNOTE-412 study represent a further important addition to our understanding of how immune checkpoint inhibitors should, or should not, be combined with curative-intent chemoradiotherapy in patients with locally-advanced head and neck cancers.” said Kevin Harrington, The Institute for Cancer Research, London, UK, not involved in the study.
Commenting on the results, Harrington added: “In this study, pembrolizumab given as a lead-in dose, concomitantly with chemoradiotherapy and then adjuvantly for one year failed to deliver a statistically significant improvement in event-free survival as a primary endpoint when compared with placebo. Even though there was a trend in favour of the pembrolizumab arm in the intention-to-treat and PD-L1-positive (CPS>/=1) populations, the current study cannot be interpreted as an indication for use of anti-PD1 therapy in combination with chemoradiotherapy in any patient group. Indeed, in light of the recent presentations of negative findings from the Javelin-100 Head and Neck, REACH and Pembro-Rad studies, these data should signal the need for a change in thinking in how to design optimal combination regimens. Focus is now likely to shift to neoadjuvant and true adjuvant therapy approaches.”