Pembrolizumab prolongs survival in recurrent, metastatic head and neck squamous cell carcinoma

CHICAGO — Pembrolizumab extended OS compared with standard chemotherapy for patients with relapsed or metastatic head and neck squamous cell carcinoma, according to randomized phase 3 study results presented at American Association for Cancer Research Annual Meeting.

Researchers also reported “an enhanced benefit” with pembrolizumab (Keytruda, Merck) for patients with PD-L1-expressing tumors.

“These data — along with the safety data — are indeed showing a place for PD-1 inhibition in the context of head and neck cancer, and this warrants further investigation,” Denis Soulieres, MD, MSc, FRCPC, director of special hematology laboratory and molecular biology at Centre de Recherche due Centre Hospitalier de l’Université de Montréal, said during a presentation.

In the multicenter, open-label KEYNOTE-040 study, Soulieres and colleagues compared the anti-PD-1 monoclonal antibody pembrolizumab with standard of care for patients with recurrent or metastatic HNSCC.

The analysis included 495 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx who developed recurrence or progressive disease after a platinum-containing regimen.

Researchers randomly assigned patients 1:1 to pembrolizumab 200 mg every 3 weeks for 24 months, or investigator’s choice of methotrexate, docetaxel or the EGFR inhibitor cetuximab (Erbitux, Eli Lilly).

OS in the intention-to-treat population served as the primary endpoint. Key secondary endpoints included OS for patients with PD-L1 combined positive score (CPS) of 1 or higher, as well as PFS in the intention-to-treat population and among patients with PD-L1 CPS of 1 or higher.

OS and PFS among patients with PD-L1 tumor proportion score of 50% or higher served as prespecified exploratory endpoints.

Survival data from several patients were outstanding when the final analysis of the trial was presented.

At AACR, Soulieres presented full OS and PFS data that used the same data cutoff date but included the full survival acquisition.

In the intention-to-treat population, pembrolizumab conferred a statistically significant OS benefit (median, 8.4 months vs. 6.9 months; HR = 0.8; 95% CI, 0.65-0.98), but the PFS benefit was not statistically significant (median, 2.1 months vs. 2.3 months; HR = 0.96; 95% CI, 0.79-1.16).

Researchers also analyzed results to determine the effect of treatment on those with CPS of 1 or higher (n = 196 for pembrolizumab, n = 191 for standard of care) and those with tumor proportion score of 50% or higher (n = 64 for pembrolizumab, n = 65 for standard of care).

Among those with CPS of 1 or higher, pembrolizumab conferred a statistically significant OS advantage (median, 8.7 months vs. 7.1 months; HR = 0.58-0.93).

Among those with tumor proportion scores of 50% or higher, pembrolizumab-treated patients demonstrated statistically significant benefits in median PFS (3.5 months vs. 2.1 months; HR = -.58; 95% CI, 0.39-0.86) and median OS (11.6 months vs. 6.6 months; HR = 0.53; 95% Ci, 0.35-0.81).

“The treatment effect of pembrolizumab seems to be better and higher for the population that is expressing PD-L1, either defined by CPS or tumor proportion score at 50%,” Soulieres said. “There is an apparent confounding effect on subsequent immune checkpoint inhibitors.”

Pembrolizumab now is being investigated in the first-line metastatic setting, as well as in the context of locally advanced disease, Soulieres said. – by Mark Leiser

Reference:

Soulieres D, et al. Abstract CT115. Presented at: American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.

Disclosure s : Soulieres reports relationships with Merck. Please see the abstract for all other authors’ relevant financial disclosures.