More evidence supporting the addition of perioperative pembrolizumab to standard care in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) has come from early findings of the Phase III Keynote-689 study.

The multicentre international trial, funded by drug company MSD, investigated whether adding neoadjuvant and adjuvant pembrolizumab to standard care – surgery with postoperative radiotherapy, with or without concurrent chemotherapy – improved outcomes in 714 patients with LA-HNSCC.

An interim analysis after a median follow-up of 38.3 months found that adding pembrolizumab significantly improved event-free survival and the major pathological response rate, especially among those with a high PD-L1 expression, compared with standard care alone.

Now a separate analysis of exploratory efficacy endpoints at 36 months, presented at ASCO’s annual meeting in Chicago, has shown median distant metastases-free survival (DMFS) of 51.8 months in the pembrolizumab arm compared with 35.7 months in the control group (HR 0.71), and an estimated DMFS rate of 59.1% versus 49.0%, respectively. 

Second head and neck or other cancers occurred in nine (2.5%) pembrolizumab recipients and 18 patients (5.1%) on standard care alone, according to the study’s abstract (link here).

The cumulative incidence of locoregional progression or recurrence was 13.4% and 14.3%, respectively, and the HR for risk of a locoregional failure event with added pembrolizumab compared with standard care alone was 0.92.

The incidence of treatment-related adverse events was similar between groups.

Additional follow-up for overall survival is ongoing.

One of the researchers, Kevin Harrington, Professor of Biological Cancer Therapies at the ICR and a consultant oncologist at The Royal Marsden NHS Foundation Trust, said standard-of-care for patients with newly-diagnosed LA-HNSCC has not changed in over two decades. 

This is the first time that immunotherapy has been shown to be successful in this group, and it could “change the world” for them, Professor Harrington said.

“The results of this trial show that pembrolizumab dramatically increases the duration of disease remission – for years longer than the current standard treatments. It works particularly well for those with high levels of immune markers, but it’s really exciting to see that the treatment improves outcomes for all head and neck cancer patients, regardless of these levels.”