It’s my pleasure to share with you the phase II randomised trial GORTEC 2015-01 PembroRad, pembrolizumab versus cetuximab concomitant with radiotherapy in locally advanced head and neck squamous cell carcinoma. Cetuximab and radiotherapy is the standard of care for patients unfit to receive high dose cisplatin in locally advanced head and neck squamous cell carcinoma. Pembrolizumab has been approved for the second line and then recently first line recurrent or metastatic head and neck squamous cell carcinoma.

This study was based on the hypothesis of a potential synergistic effect of the anti-PD-1, pembrolizumab, when combined with radiotherapy. This combination was tested in this randomised trial versus cetuximab radiotherapy in locally advanced head and neck cancer.

In fact, in this trial we randomised the patients to two arms – control arm with weekly cetuximab and radiotherapy while in the experimental arm pembrolizumab every three weeks, 200mg, and radiotherapy, three cycles in total. We included 173 patients especially stage 3 and 4 head and neck cancer patients unfit for receiving high dose cisplatin. The treatment compliance was good with more than 90 patients receiving whole dose radiotherapy in both arms. Nearly 90% of patients received three cycles of whole dose pembrolizumab which showed significantly less grade 3 or grade 4 adverse events including radiodermatitis, rash and mucositis in the pembrolizumab radiotherapy arm than in the cetuximab radiotherapy arm.

With a median follow-up of more than two years we showed the primary endpoint of local regional control at 15 months after radiotherapy, about 60% for both arms, no significant difference. We did not find any difference between the two arms in terms of progression free survival or distant metastasis. Two year overall survival was 62% for the pembrolizumab and radiotherapy arm while 55% for the cetuximab radiotherapy arm with a hazard ratio of 0.83 and a p-value of 0.49.

What can be learned from the results? Will standard of care be influenced?

In fact, for the patients unfit to receive the high dose cisplatin because our phase II trial did not meet the primary endpoint, no difference of local regional control, no overall survival, so the treatment could not be changed, it’s still cetuximab and radiotherapy. We are still waiting for the results by PD-L1 status that is ongoing in our GORTEC.

However, we know that the toxicity profiles were quite different between the pembrolizumab arm and the cetuximab arm with significantly more grade 3 or grade 4 adverse events with cetuximab and radiotherapy. We think we should still try other combinations, maybe by pembrolizumab concomitant and adjuvant or other combinations, probably neoadjuvant pembrolizumab or other PD-1 or PD-L1 inhibitors with radiotherapy.

Is there anything you would like to add?

In fact we are still awaiting other phase III trials such as our GORTEC REACH trial which combined avelumab and cetuximab and radiotherapy compared with cetuximab and radiotherapy in unfit patients. And also we are waiting for the results of KEYNOTE-412 – pembrolizumab and cisplatin and radiotherapy.

We have also another trial, the REWRITe trial, in which we use small field instead of large field radiation to avoid excessive irradiation of the lymphatic area. This could be interesting to obtain good results when combined with an anti-PD-1 or PD-L1 inhibitor.