Jean-Pascal Machiels, MD, PhD, on Head and Neck Cancer: Recent Data on Pembrolizumab and Chemoradiation Therapy

ESMO Congress 2022


Jean-Pascal Machiels, MD, PhD, of Belgium’s Cliniques universitaires Saint-Luc (UCLouvain), discusses the primary results of the phase III KEYNOTE-412 study of pembrolizumab plus chemoradiation therapy (CRT) vs placebo plus CRT for patients with locally advanced head and neck squamous cell carcinoma (Abstract LBA5).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
We presented at ASMO the result of the KEYNOTE-412 trial that compared chemoradiation with pembrolizumab versus chemoradiation plus placebo in patient with locally advanced squamous cell carcinoma of the head and neck. The standard therapy for this group of patient when they're unresected is high-dose cisplatin combined with radiation therapy. With this treatment, the 5-year of our survival is around 50%. We clearly need to improve that. We know that pembrolizumab improves survival in the recurrent and metastatic setting. We have also preclinical model that demonstrate when you gave radiation therapy or cisplatin, that you increase the PD-L1 expression on the tumor, and there are also in preclinical model data that suggests that combining radiotherapy plus anti-PD-1 could improve the outcome. In this study, we select patients unresected, so locally advanced squamous cell carcinoma, and we include patients with locally advanced disease, meaning stage 3 and stage 4 patient. For p16-positive oropharyngeal cancer, we include only T4 or N3 disease. The patients were randomized, so we include 804 patient, randomized 1:1 fashion between chemoradiation plus placebo versus chemoradiation plus pembrolizumab. We gave one dose of placebo or pembrolizumab one week before the cycle of chemoradiation, and in total, we gave 17 cycles. The primary endpoint was event-free survival. The primary endpoint in this trial on the intent-to-treat population was not met, but we observe a favorable trend in favor of improved event-free survival in the group of patients that received chemoradiation plus pembrolizumab. The hazard ratio was 0.83 and the p-value, 0.04, but the efficacy boundary was 0.02 in this study. The 2-year event-free survival with was 56% in placebo and 63% in pembrolizumab. After that, we performed an exploratory analysis where we look at patient with a high expression of PD-L1 on their tumor, CPS 20 or higher. In this group of patients, the 2-year event-free survival was, in placebo, 62%, and in pembrolizumab, 71%. For this group of patients, we also observe a favorable of overall survival benefit, with a 3-year of a survival rate of 73% in control and 79% in pembrolizumab. So we conclude by saying that this trial did not meet the primary endpoint, although there is a favorable trend in favor of pembrolizumab with chemoradiation. This study gave important information, because probably we need to select the patient altered exploratory. It seemed that patients with high CPS score on the tumor could benefit of this approach. So future trials should probably try to select patient with a tumor that express PD-L1. Maybe also in the future, we should try to combine differently chemoradiation with pembrolizumab. Probably the adjuvant setting or the neoadjuvant setting will be better than the concomitant treatment.

Related Videos

Solid Tumors

Bernd Kasper, MD, PhD, on Desmoid Tumors: Results on Nirogacestat vs Placebo

Bernd Kasper, MD, PhD, of Germany’s Mannheim Cancer Center, discusses phase III data from the DeFi trial, the largest study conducted to date for patients with desmoid tumors. The trial showed that the gamma secretase inhibitor nirogacestat demonstrated improvements in all primary and secondary efficacy endpoints. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and, occasionally, mortality in patients (Abstract LBA2).

Pancreatic Cancer

Christelle de la Fouchardiere, MD, on Pancreatic Ductal Adenocarcinoma: Phase III Trial Results With Gemcitabine Plus Paclitaxel

Christelle de la Fouchardiere, MD, of France’s Centre Léon Bérard, discusses phase III findings from the PRODIGE 65–UCGI 36–GEMPAX UNICANCER study, which evaluated whether the combination of gemcitabine and paclitaxel improves overall survival compared with gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma after FOLFIRINOX failure or intolerance (Abstract LBA60).

Skin Cancer

John B.A.G. Haanen, MD, PhD, on Melanoma: Phase III Data on Treatment With Tumor-Infiltrating Lymphocytes vs Ipilimumab

John B.A.G. Haanen, MD, PhD, of The Netherlands Cancer Institute, discusses recent phase III findings, which show that tumor-infiltrating lymphocytes (TILs) improve progression-free survival compared with ipilimumab by 50% in patients with advanced melanoma after not responding to anti–PD-1 treatment. Around 50% of TIL-treated patients had a response, and 20% had a complete response (Abstract LBA3).

Kidney Cancer

Toni K. Choueiri, MD, and Laurence Albiges, MD, PhD, on RCC: Recent Phase III Data on Cabozantinib, Nivolumab, and Ipilimumab From the COSMIC-313 Trial

Toni K. Choueiri, MD, of the Dana-Farber Cancer Institute, and Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discuss phase III findings showing that cabozantinib in combination with nivolumab and ipilimumab reduced the risk of disease progression or death compared with the combination of nivolumab plus ipilimumab in patients with previously untreated advanced renal cell carcinoma of IMDC (the International Metastatic RCC Database Consortium) intermediate or poor risk. However, the combination of cabozantinib, nivolumab, and ipilimumab vs nivolumab plus ipilimumab did not demonstrate an overall survival benefit to patients (Abstract LBA8).

Breast Cancer

Marleen Kok, MD, PhD, on Triple-Negative Breast Cancer: Nivolumab Monotherapy or in Combination Therapy

Marleen Kok, MD, PhD, of The Netherlands Cancer Institute in Amsterdam, discusses the initial results from the BELLINI trial, which tested whether short-term preoperative nivolumab, either as monotherapy or in combination with low-dose doxorubicin or novel immunotherapy combinations, can induce immune activation in patients with early-stage triple-negative breast cancer with tumor-infiltrating lymphocytes (Abstract LBA13).