Prof Jean-Pascal Machiels presents the primary results of the phase 3 KEYNOTE-412 study. The study explored pembrolizumab (pembro) with chemoradiation therapy (CRT) vs placebo plus CRT for locally advanced head and neck squamous cell carcinoma.

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