Keytruda Regimen May Improve Event-Free Survival in Head and Neck Squamous Cell Carcinoma

The KEYNOTE-689 trial assessing Keytruda (pembrolizumab) for the perioperative treatment of newly diagnosed stage 3 or 4A, resected, locally advanced head and neck squamous cell carcinoma met its primary end point of event-free survival, according to a press release from Merck, the drug’s manufacturer.

When a trial meets its primary end point, this means that it met its main objective which was determined at the beginning of the trial. In this case, the primary end point was event-free survival, which is the length of time after treatment when a patient does not experience events or complications that the treatment was meant to delay or prevent, according to the National Cancer Institute.

“These results are substantial, as KEYNOTE-689 marks the first positive trial in two decades for patients with resected, locally advanced head and neck squamous cell carcinoma,” Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in the release. “These statistically significant and clinically meaningful findings have the potential to be practice-changing and continue to highlight the promising role of Keytruda for certain patients with earlier stages of disease.”

The phase 3 KEYNOTE-689 trial evaluated Keytruda as neoadjuvant therapy (treatment as the first step to shrink a tumor before the main treatment is administered), followed by surgery plus standard-of-care radiotherapy with or without cisplatin as adjuvant therapy (additional treatment after the primary treatment to reduce the risk that the cancer returns). This was then followed by Keytruda maintenance therapy, according to the release. This regimen was compared with adjuvant radiotherapy with or without cisplatin alone.

Researchers conducting this study enrolled approximately 704 treatment-naïve patients with newly diagnosed, stage 3 or 4A resected locally advanced, head and neck squamous cell carcinoma

In addition to a significant and clinically meaningful improvement in event-free survival, the Keytruda perioperative treatment regimen also significantly improved major pathological response compared with adjuvant radiotherapy alone.

Researchers noted a trend towards improvements in overall survival (the time when a patient with cancer is still alive) in patients treated with the Keytruda regimen compared with standard-of-care radiotherapy. As noted in the press release, the results related to overall survival were not statistically significant when assessed in patients whose tumors were PD-L1 Combined Positive Score of 10 or higher. Of note, patients with a high score indicates that PD-L1 is significantly expressed on tumor cells. The National Cancer Institute notes that PD-L1 is a protein that acts like a brake to keep immune responses under control.

The safety profile with Keytruda observed in the KEYNOTE-689 trial was consistent with previously reported studies, with no new safety signals identified by researchers.

Keytruda has previously been approved by the Food and Drug Administration as monotherapy and in combination with other therapies for some patients with metastatic or unresectable, recurrent head and neck squamous cell carcinoma. Indications of Keytruda include use with platinum and fluorouracil for first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma; single-agent Keytruda for first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma whose tumors express PD-L1; and single-agent Keytruda for recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy, according to the release.

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