Stuart J. Wong, MD, on Adjuvant Regimen in Resected HNSCC

We have been treating resectable head and neck cancer the same for two decades. It has been defined by a couple of clinical trials, an EORTC trial and RTOG trial examining patients for high-risk resected head and neck cancer where patients were randomized to either radiation alone or radiation plus cisplatin. That study was positive and that's how we've been treating patients for two decades—radiation plus high-dose intermittent cisplatin. There have been many attempts to try to improve upon this over the years and probably the biggest area of research has been with radiation, including immunotherapy to that mixture. There have been maybe about six large randomized trials that have combined radiation and immunotherapy and all of those were unfortunately negative. And then this year we had the NIVOPOSTOP trial. So this was a study that enrolled nearly 700 patients and patients were randomized to the standard treatment of radiation-cisplatin versus radiation, cisplatin, and nivolumab. So this study had a primary endpoint of disease-free survival and it was positive. So this is very exciting. From what we can tell, this is a very well-conducted study. The control arm performed very well. It really checks all the boxes for a phase three randomized trial in terms of what we look for—a well-conducted study of interest. This study had an examination of PD-L1 expression. And unlike some of the previous studies, there's a real strong signal that the PD-L1 positive patients had a really strong correlation with clinical outcome. And this probably is the feature that maybe was the difference between this study being positive versus previous generations of studies that were negative. So what does this mean in terms of patient care? Well, we still need more information from this study. There needs to be mature overall survival data. We're looking for other information about maybe granular detail about the PD-L1 positive patients and subgroups. Perhaps one of the biggest things that I think will have an impact on how we integrate this treatment into clinical practice is another big study that was presented this year, and it's called the KEYNOTE-689 study. So this study was a little bit different. Patients got neoadjuvant pembrolizumab followed by surgery, followed by adjuvant pembrolizumab and combined modality therapy. And this study was also positive. So the big difference between these two studies—the KEYNOTE-689 study was neoadjuvant, the NIVOPOSTOP study was purely adjuvant—and the patterns of failure were really different in the studies. The NIVOPOSTOP study was primarily an improvement of locoregional control, and the KEYNOTE-689 study was primarily an improvement in distant metastatic disease. Very confusing. We think we have some idea about why that may be, but this will definitely come into discussion if both of these treatments come into practice.