KEYNOTE-689 Findings May Reshape Resectable Head and Neck Cancer Care: Ravindra Uppaluri, MD, PhD

In part 2 of this interview, Ravindra Uppalurdi, MD, PhD, director of head and neck surgical oncology at Dana-Farber Brigham Cancer Center, lead investigator of the phase 3 KEYNOTE-689 trial (NCT03765918), speaks with The American Journal of Managed Care® (AJMC®) about how the study's findings could reshape the standard of care for patients with resectable, locally advanced head and neck squamous cell carcinoma. He also highlights key areas for further research.

Uppaluri presented the KEYNOTE-689 trial results earlier today at the American Association for Cancer Research Annual Meeting 2025 in Chicago. Watch part 1 of his interview with AJMC to learn more about the study's objectives and key findings.

This transcript has been lightly edited; captions were auto-generated.

Transcript

How might the phase 3 KEYNOTE-689 trial results influence clinical practice for resectable locally advanced head and neck squamous cell carcinoma? What is needed to support the broader adoption of this strategy?

I think this is the most exciting part of this. These data really support that neoadjuvant pembrolizumab (Keytruda; Merck) followed by surgery and adjuvant pembrolizumab, concurrent with and after post-operative chemoradiotherapy or radiotherapy alone, really represents a new standard of care for the treatment of patients with respectable, locally advanced head and neck cancer.

The data are compelling enough for me to say that this should be the new standard of care for these patients, especially in the locally advanced resectable setting. These trials are very complicated to do, and part of the reason they succeed is because of a multidisciplinary integration of surgeons, medical oncologists, and radiation oncologists. I like to use the phrase, and it's a common phrase, but it takes a village to manage these patients, and that's what it's going to take going forward.

I think the commitment to multidisciplinary care will be really required to bring these findings to the real-world setting for all patients. In the past, there would be single specialties involved in different phases, but it's very clear from these studies that if a surgeon sees a patient, a medical oncologist needs to be involved early to help deliver the immunotherapy.

I think a lot more integration like that will be required. It will change the workflow, but it'll emphasize, again, that to get these good outcomes, you need the sort of strong ties amongst the multidisciplinary group.

Are there any unanswered questions or areas for future research that you're particularly interested in exploring?

From my perspective, it's really an exciting time in head and neck cancer because of these positive findings. In the future, there are a couple of different directions to go. First, this trial included both a neoadjuvant phase and an adjuvant phase of delivering pembrolizumab. It really didn't dissect apart which one of those 2, or if both, are required to get the outcomes that we saw. I think one of the key questions going forward will be this idea of contribution of components, which is which side is important, or do you need both sides of immunotherapy centered around surgery? So, that's one key question.

Additional questions that this allows us to ask now are, can you use different immunotherapies to achieve even better results than we're seeing here? There are many other immune checkpoint blockade targets available. Whether additional targeting would improve the pathologic responses that I mentioned and ultimately better clinical outcomes is a very important question that I think this will now allow us to ask.