Merck's Keytruda Shows Promise in Head and Neck Cancer Treatment

Merck's blockbuster PD-1 inhibitor Keytruda has demonstrated significant survival benefits in patients with head and neck squamous cell carcinoma (HNSCC), according to interim results from the Phase III KEYNOTE-689 study presented at the 2025 Annual Meeting of the American Association for Cancer Research (AACR).

Keytruda Improves Event-Free Survival

The study revealed that perioperative Keytruda improved event-free survival (EFS) by 27% in the intention-to-treat population compared to a perioperative radiotherapy regimen. EFS is defined as the first case of radiographic progression, recurrence, local or distant progression, or death due to any cause.

Subgroup analyses indicated that Keytruda's efficacy in this indication scales according to PD-L1 expression, as measured by the Combined Positive Score (CPS). In patients with high expression levels of PD-L1, Keytruda lowered the likelihood of EFS events by 34% versus perioperative radiotherapy.

Secondary Endpoints and FDA Review

Keytruda also significantly improved major pathological response, a key secondary endpoint, in the intention-to-treat population—demonstrating a treatment benefit of 9.3% versus adjuvant radiotherapy alone. Overall survival trended in Keytruda's favor, though only in a subset of patients and with a magnitude of effect that fell short of statistical significance. The KEYNOTE-689 study will continue to follow patients for overall survival analysis.

Merck has already submitted a supplemental Biologics License Application (sBLA) for Keytruda in this indication, which is currently under review by the FDA. The target action date for the FDA's decision is set for June 23.

Market Impact and Industry Outlook

While the results are promising, analysts at William Blair caution that the market impact might be limited. In a Monday morning note, they stated, "While this benefit is likely to support adoption of Keytruda in the perioperative HNSCC setting, we maintain our view that this ultimately has less than a 10% impact on the metastatic HNSCC population."

The readout is expected to affect potential uptake in the space for other companies with similar outlooks, such as Merus's bispecific antibody petosemtamab and Exelixis's oral tyrosine kinase inhibitor zanzalintinib. Analysts had previously projected that risk reduction in KEYNOTE-689 would be "likely lower than 40%," which was confirmed by the interim results.

As the pharmaceutical industry continues to advance in cancer treatment, Keytruda's performance in head and neck cancer represents a significant step forward, potentially offering new hope for patients with this challenging diagnosis.