Perioperative Pembro Approved to Up Chance of HNSCC Cure

The FDA has approved a before and after surgery regimen for pembrolizumab to improve outcomes in resectable locally-advanced head and neck squamous cell carcinoma (HNSCC).

Specifically, the new approval is for HNSCC tumors that express PD-L1, with pembrolizumab as a single agent in the neoadjuvant setting, followed by radiation plus/minus cisplatin after surgery, and continuing as a single agent for maintenance.

FDA said the approval is the first for HNSCC in 6 years, but it is also another approval for a perioperative immunotherapy cancer regimen. 

Oncologists and the agency have been frustrated that company trials don’t include an arm to answer the question of if immunotherapy helps both before and after surgery, of if one or the other is enough. 

Even so, Barbara Burtness, MD, a head and neck oncologist at Yale University, Connecticut, told Medscape Medical News that she’ll offer the new pembrolizumab regimen to resectable patients given the strength of pembrolizumab’s approval trial, KEYNOTE-689, because it offers the chance of a cure when tumors are resectable. 

“Many of us think it’s the new standard of care,” she told Medscape. 

KEYNOTE-689 was a multicenter, open-label trial that included 682 patients with resectable stage III-IVa disease whose tumors had a PD-L1 combined positive score of at least 1. Approval was based on the 682 patients, not the total population of 714. 

Half the subjects were randomized to the current standard of care: upfront surgery followed by radiotherapy with or without cisplatin. The other half were randomized to pembrolizumab add-on: 200 mg pembrolizumab every 3 weeks for two cycles before surgery, then pembrolizumab 200 mg every 3 weeks for three cycles afterwards with radiotherapy plus/minus cisplatin, followed by pembrolizumab at the same dose every 3 weeks for 12 cycles as maintenance. 

Cisplatin was added after surgery if patients were at high risk for recurrence, meaning that tumor removal was not complete or patients had spread beyond their lymph nodes. 

Median event-free survival was 59.7 months with pembrolizumab vs 29.6 months without it (hazard ratio, 0.70; P =.00140). Overall survival was immature, but there was no decrease with pembrolizumab add-on. 

There were no new safety signals in the trial. Pembrolizumab labeling warns of immune-mediated adverse events, infusion-related reactions, and embryo-fetal toxicity; 1.4% of pembrolizumab subjects in KEYNOTE-689 were not able to have surgery because of side effects.

FDA noted pembrolizumab should be administered before chemotherapy when given on the same day.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected]