Improving the Management of HNSCC: Next Steps

Victoria Meucci Villaflor, MD: With solid tumor oncology moving more toward precision medicine or personalized medicine, where do you think head and neck cancer is going?

Cesar Perez, MD: The data that we discussed from the RUN-HN trial have shown us that there’s a role for personalized medicine in head and neck cancer. We’ve seen more value in sequencing for this population that we weren’t finding much before, besides checking for PD-L1 by immunohistochemistry. Next-generation sequencing probably has a new role in this disease. I hope that this is just the tip of the iceberg of what we can accomplish by doing sequencing on our patients with head and neck cancer.

Victoria Meucci Villaflor, MD: Dr Perez, are you using next-generation sequencing on all of your patients with head and neck cancer?

Cesar Perez, MD: Yes. Until recently, we weren’t finding that much value in doing next-generation sequencing in patients with head and neck squamous cell carcinoma. But based on all the trials in clinical development, I’m now doing next-generation sequencing on every patient in the metastatic and recurrent setting to find those patients with a high TMB [tumor mutational burden], for example, who might not have good PD-L1. But I’m mainly doing it for clinical trial purposes, so we can then try to find driver mutations where we can put the patients on clinical studies, as they did with this trial on tipifarnib in patients with HRAS mutations.

Victoria Meucci Villaflor, MD: At City of Hope, we also sequence all of our metastatic patients as they come in. It would be fair to say that we gather some information out of this, even though it’s early in the development in squamous cell head and neck cancers, at least as far as putting patients on clinical trials.

Cesar Perez, MD: Definitely. That’s the way to go. We need to find options for this population beyond the approved options. The only way to do that is trying to sequence more patients and offering novel clinical studies to this population. That’s what they deserve.

Victoria Meucci Villaflor, MD: What do you feel are the important next steps?

Cesar Perez, MD: We have the data from the trial with tipifarnib for patients with HRAS mutations, and I feel that they are exciting data. It’s a small study. That’s what we need. We just need a larger trial that confirms this finding, and that is what’s being done right now with the AIM-HN study—the head and neck AIM study—in which tipifarnib is being studied in patients with head and neck squamous cell carcinoma with HRAS mutations. They also have a second cohort, an observational cohort, to analyze the effect of the first main therapy on patients with or without HRAS mutations. That trial is a lot largerthan this. More than 200 patients are trying to enroll. That’s a multicenter worldwide trial. That’s definitely the next step. We want to see confirmatory and positive data, and that’s what they’re working on.

Victoria Meucci Villaflor, MD: What are the next clinical trials to build on the work that’s already been done in this arena?

Cesar Perez, MD: Obviously that trial, but we need to try to extend the benefit of these agents to a larger population. Trying to extend the benefit of the farnesyltransferase inhibitor toward a larger population is the way to go. You’re probably familiar with the KURRENT trial. What do you think about that approach, trying to give tipifarnib with a PIK3CA inhibitor for a larger population that we have been trying to treat for a long time with targeted therapy?

Victoria Meucci Villaflor, MD: That’s a very interesting concept. Often, many of these tumors are able to escape some of these inhibitors because they’ll go upstream or downstream to somehow circumvent the mechanism of action and can become resistant to it. I found a lot of the in vitro and early in vivo work looking at alpelisib and tipifarnib in the KURRENT trial very interesting and promising. I’m looking forward to seeing results of this in human subjects.

Cesar Perez, MD: Yes, I agree. PIK3CA is a way more common genomic abnormality in head and neck cancer. The exciting thing is that with the relationship between HRAS and PIK3CA being downstream, blocking the 2 pathways, as we have done in melanoma with BRAF and MEK, has been a success story. Doing it in head and neck is the way to go. As we have discussed before, PIK3CA alone is not going to cut it for a patient with head and neck cancer. But both the farnesyltransferase inhibitor and trying to block that HRAS escape route, and then blocking it with alpelisib—a drug that we already know is active in patients with breast cancer with PIK3CA mutated tumors—is the way to go. I’m excited about it. It’s a very smart approach to try to treat this disease.

Victoria Meucci Villaflor, MD: All in all, head and neck cancer is finally beginning to get into a situation where we’re able to target a lot of these molecules, and I’m looking forward to the years ahead where we’ll probably be able to target even more molecules. And looking at the different combinations in an effort to circumvent a lot of resistance mechanisms will also be a lot of work that’s to come for us.

Cesar Perez, MD: Definitely. In a couple of years, we’ll see sequencing have greater value. We’re able to inhibit and treat tumors with those specific genomic abnormalities. Then sequencing will be considered a must, as it is with patients with non–small cell lung cancer who you treat every day. It’s very exciting, and I’m hoping that these studies will bring some light to how to benefit and improve survival for this population that is in so much need.

Victoria Meucci Villaflor, MD: What would be your testing recommendations to other oncologists who might not specialize in head and neck cancer like us?

Cesar Perez, MD: We first need to acknowledge that we have a marker now. It’s been proven in an early trial that it’s potentially active. We need to put the word out that patients with neck and head cancer need to be tested. There needs to be sequencing of patients with head and neck cancer. There are potential options out there that are very promising, but the only way to try to put the patients on trial and prove that is doing the testing. We have to extend all these efforts in testing from other tumors into the head and neck cancer world and put the word out that this trial, RUN-HN, was at least a very promising strategy that gave us some data. They’re early data, but we have some data. We certainly should start testing all these patients, like you guys do at City of Hope and we do here at the Sarah Cannon Research Institute at Florida Cancer Specialists.

Transcript edited for clarity.