Pembrolizumab provided a clinically meaningful OS extension compared with standard-of-care therapy among patients with recurrent head and neck squamous cell carcinoma, according to results from the randomized phase 3 KEYNOTE-040 study published in The Lancet.
Researchers also reported that pembrolizumab (Keytruda, Merck) had a favorable safety profile with no new safety signals.
“The results of this study solidify the role of PD-1 checkpoint inhibition in the treatment of head and neck squamous cell carcinoma,” Ezra E.W. Cohen, MD, associate director of Moores Cancer Center at UC San Diego Health, and colleagues wrote.
Researchers compared the safety and efficacy of pembrolizumab with standard-of-care treatment among 495 patients (median age, 60 years; range, 54-66) with head and neck squamous cell carcinoma that either advanced during or after platinum-containing treatment for recurrent or metastatic disease or recurred or progressed within 3 to 6 months of prior multimodal, platinum-containing treatment for locally advanced disease.
Cohen and colleagues randomly assigned participants to 200 mg IV pembrolizumab every 3 weeks (n = 247) or investigator’s choice of standard doses of IV methotrexate, docetaxel or cetuximab (Erbitux, Eli Lilly; n = 248).
OS in the intention-to-treat population served as the study’s primary endpoint. Researchers assessed safety in the as-treated population.
Median follow-up was 7.5 months (interquartile range [IQR], 3.4-13.3), including 8.4 months (IQR, 3.3-14.5) in the pembrolizumab group and 7.1 months (IQR, 3.7-12.4) in the standard-of-care group.
By data cutoff on May 15, 2017, 181 patients (73%) in the pembrolizumab group and 207 patients (83%) in the standard-of-care group had died (HR for death = 0.8; 95% CI, 0.65-0.98).
Among the intention-to-treat population, pembrolizumab yielded median OS of 8.4 months (95% CI, 6.4-9.4) vs. 6.9 months (95% CI, 5.9-8) with standard-of-care therapy (HR = 0.8; 95% CI, 0.65-0.98).
Twelve-month survival reached 40% (95% CI, 33-47) in the pembrolizumab group and 26% (95% CI, 20-33) in the standard-of-care group.
Researchers reported 300 deaths among the 387 study participants with a PD-L1 combined positive score of 1 or higher, including 138 in the pembrolizumab group and 162 in the standard-of-care group.
Fewer patients in the pembrolizumab group experienced grade 3 or worse treatment-related adverse events compared with the standard group (13% vs. 36%).
The most common treatment-associated adverse events were hypothyroidism (n = 33; 13%) in the pembrolizumab group and fatigue (n = 43; 18%) the standard-of-care group. Four patients in the pembrolizumab group died of causes related to treatment (large intestine perforation, malignant neoplasm progression, Stevens-Johnson syndrome and unspecified cause), compared with two treatment-related deaths in the standard of care group (malignant neoplasm progression and pneumonia).
In a related editorial, Barbara Wollenberg, MD, professor at the department of otorhinolaryngology, head and neck surgery at University Clinic of Schleswig Holstein in Lubeck, Germany, discussed the promise of these findings.
“Cohen and colleagues’ study might prove to be an argument to alter guideline-based treatment of patients with head and neck squamous cell carcinoma and implement PD-1-targeting antibodies in standard care in the setting of second-line treatment failure,” Wollenberg wrote. “The publication of the first data from the KEYNOTE-048 study, presented during [European Society for Medical Oncology 2018 Congress], represents another major study having the potential to alter treatment guidelines as it shows the superiority of pembrolizumab over the EXTREME regimen, which could shift the use of PD-1 antibodies to standard care of patients with head and neck squamous cell carcinoma already in the setting of first-line treatment failure.” – by Jennifer Byrne
Disclosures: Cohen reports grant support to his institution from Merck Sharp & Dohme for clinical research related to the submitted work and advisory roles with AstraZeneca, Bristol-Myers Squibb, Eisai, Human Longevity, Merck and Pfizer. Please see the study for all other authors’ relevant financial disclosures. Wollenberg reports no relevant financial disclosures.