Real-World Considerations for Perioperative Pembrolizumab in Locally Advanced Head and Neck Squamous Cell Carcinoma
Key Clinical Takeaways:
- Perioperative pembrolizumab represents a major clinical advance for locally advanced head and neck squamous cell carcinoma, offering new neoadjuvant and adjuvant treatment options for patients with historically poor long-term survival, particularly in advanced oral cavity and laryngeal cancers.
- Implementation raises substantial financial and logistical considerations, as the 17-cycle perioperative regimen carries significant payer costs, potential patient financial toxicity, and added treatment burden related to prolonged therapy duration, transportation, and time away from work.
- Key unanswered questions remain regarding optimal patient selection and treatment sequencing, including the relative contributions of neoadjuvant versus adjuvant therapy, age-related benefit, tumor subsite differences, and how evolving policy frameworks such as the Inflation Reduction Act may influence real-world adoption.
Lauren Miller, MD, The Ohio State University, Columbus, Ohio, examines the real-world challenges and opportunities associated with implementing perioperative pembrolizumab following its FDA approval for patients with resectable, locally advanced PD-L1–positive head and neck squamous cell carcinoma.
Transcript:
My name is Lauren Miller, I am an assistant professor of otolaryngology, head and neck surgery, at The Ohio State University. Myself, along with my coauthors, James Rocco and Vinay Rathe, also at The Ohio State, published a viewpoint in JAMA Otolaryngology about pembrolizumab use in head and neck cancer.
This was really written as a viewpoint in response to the recent KEYNOTE-689 pivotal study, which was published and subsequently led to FDA approval of pembrolizumab as neoadjuvant and adjuvant use for perioperative, locally advanced head and neck squamous cell carcinoma. In the head and neck squamous cell carcinoma world, this is a huge advancement, and KEYNOTE-689 offers a lot of potential for our patients. We know that our patients who have advanced-stage oral cavity and laryngeal cancer generally have a very low overall survival, over 5 years, and so having adjuvant treatment options to try and help with them is a substantial advancement in our field.
Our viewpoint focused a little less on some of the clinical details of the trial and more on some of the budgetary consequences, both from a hospital level, a national health care level, and then also patient financial toxicity, as well as some general policy implications. Some of the conversation around incorporating neoadjuvant and adjuvant pembrolizumab in our patient population really revolves around the fact that KEYNOTE-689 had a total of 17 cycles, 2 neoadjuvant and 15 adjuvant, which amounts to about over 200,000 dollars in spending by insurance. We extrapolated that across all potentially eligible head and neck cancer patients, this might amount to over 4 billion dollars in all insurer spending.
Obviously, overall spending is not the only way to look at this, formal cost-effectiveness studies are essential in this world, but they have not been done yet, and we do not have formalized overall survival data yet, so there is definitely still a lot more to be seen in how this would impact our field, but nonetheless, it is not just payer burden, it is also patient burden.Besides the obvious cost and deductibles spanning over 2 different years, which would lead most patients to hit their deductibles and copays over the span of 2 years, there is also a lot of transportation barriers, and going through 17 cycles comes with significant burden, both from taking off time from work and transportation and health care burden for a lot of patients, so considering some of the effects of that as well.
Like I mentioned, I think there is a lot to be done, there are still a lot of questions lingering on how we, as head and neck surgeons and we in head and neck cancer communities, can implement this best with the excitement that pembrolizumab can offer to our patients. But some further questions that we highlighted in this viewpoint include not just these financial questions, but also the financial questions in the scope of the Inflation Reduction Act and what is going to happen with pembrolizumab. Merck has recently obtained FDA approval for the subcutaneous version, and whether or not that is also going to be considered a novel medication or not for the Inflation Reduction Act remains to be seen.
It is unclear at this point where the contribution of pembrolizumab lies, if it is in the neoadjuvant setting versus the adjuvant setting or both and there are a lot more subgroup analyses that could be done, whether it is neoadjuvant versus adjuvant or stratified by age– there is a lack of benefit in patients over 65 years old. Tumor subsite subgroup analyses would warrant greater analyses to really understand where we can get the greatest benefit for our patients while minimizing their treatment burden in this patient population.
Nonetheless, I do think that this is a really exciting time, and I think there is a lot of excitement in our community, both not just from surgical groups, but also from medical and radiation oncology teams, to try and understand how we can best incorporate pembrolizumab for our patients and iron out some of these logistical and financial questions for them.
Source:
Miller LE, Rocco JW, Rathi VK, et al. Pembrolizumab in head and neck cancer—Promise and price. JAMA Oncol. Published online: December 18, 2025. doi: 10.1001/jamaoto.2025.4624
