Jean-Pascal Machiels, MD, Cliniques Universitaires Saint Luc, Brussel, Belgium, shares results and insights from the randomized, double-blind, phase 3 KEYNOTE-412 study, evaluating the efficacy and safety of pembrolizumab plus chemoradiation therapy in patients with locally advanced head and neck squamous cell carcinoma.

Dr Machiels reports that while this was not a positive trial in terms of statistics and it will not change practice, pembrolizumab plus chemoradiation therapy was associated with a favorable trend toward improved event-free survival (EFS) compared to placebo plus chemoradiation therapy. He also pointed out that for PD-L1 score may be a predictive biomarker for clinical benefit with this methodology.

These results were first presented at the 2022 European Society of Medical Oncology (ESMO) Congress.

Transcript:

My name is Jean-Pascal Machiels. I'm a medical oncologist working at Cliniques Universitaires Sain-Luc in Brussels. At the 2022 ESMO Congress, I presented the result of the KEYNOTE-412 trial.

This trial compared chemoradiation plus pembrolizumab versus chemoradiation plus placebo, for patients with squamous cell carcinoma of the head and neck. Patients eligible for the trial were patients with locally advanced squamous cell carcinoma of the head and neck, it was unresectable patients. There were 804 patients randomized between chemoradiation plus placebo or chemoradiation plus pembrolizumab. We started pembrolizumab or placebo 1 week before chemoradiation. It was infused every 3 weeks and we gave 17 cycles. The primary end point was [event-free survival] EFS, including not just progression, but also pathologically proved loco-regional relapse since RECIST criteria is not always able to capture whether this is progression or treatment failure in this disease.

The primary end point in this trial was indeed not met with the P-value of 0.04 in favor of the pembrolizumab arm. When we look at the 2-year EFS rate, it was 56 persons in the control arm and 63 persons in the pembrolizumab arm. The survival was similar between the 2 groups.  

We also conducted an exploratory analysis, where we selected patients for high expression of PD-L1, so PD-L1 20 or higher, and we have about 36% of the patient—quite a good number of patients, nicely balanced between the 2 group. And for this subgroup of patients in this exploratory analysis, we have a 2-year EFS that was 62 persons in the control and 73 persons in pembrolizumab. We had also an improvement in our survival with a hazard ratio of 0.67. This is just an exploratory analysis, but this suggests that PD-L1 could be a good predictive biomarker.

When we looked at the safety, there were no new safety signals. We had the classical toxicities seen with chemoradiation, and we had also some autoimmune toxicity, but nothing new for this combination.

In conclusion, we have a favorable trend to give pembrolizumab with chemoradiation, but we don't have a positive study in term of statistics. It’s not going to change the standard of care, but out data suggests that, when we measure PD-L1 by CPS score and with the methodology used in this trial, we could probably select the patients and have a good predictive biomarker. This will have to be investigated in a further trial.

Source:

Machiels J, Tao Y, Burtness B, et al. Primary results of the phase III KEYNOTE-412 study: Pembrolizumab (pembro) with chemoradiation therapy (CRT) vs placebo plus CRT for locally advanced (LA) head and neck squamous cell carcinoma (HNSCC). Presented at ESMO Congress; September 9-13, 2022; Paris, France. Abstract LBA5.