The phase III KEYNOTE-048 study compared pembrolizumab plus chemotherapy vs the EXTREME regimen in patients with recurrent/metastatic head and neck cancer.
CHICAGO-Immunotherapy combined with chemotherapy demonstrated superior overall survival (OS) in the first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma compared with the standard platinum-based chemotherapy EXTREME regimen, according to the results of the phase III KEYNOTE-048 study (abstract 6000) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
“At that [second interim] analysis [presented last year at ESMO], pembrolizumab monotherapy when compared to EXTREME resulted in improved overall survival in the PD-L1 CPS [programmed death ligand 1 combined positive scores] greater than 20 and greater than 1 populations and was noninferior in the total population, with a favorable safety profile,” said Danny Rischin, MD, of Peter MacCallum Cancer Center, who presented the results.
Rischin’s presentation provided the final protocol-specified results for the study on pembrolizumab or pembrolizumab plus chemotherapy vs the EXTREME regimen for recurrent/metastatic head and neck squamous cell carcinoma. The investigators tested for OS and progression-free survival (PFS), sequentially comparing pembrolizumab plus chemotherapy vs EXTREME in populations with CPS ≥ 20 and CPS ≥ 1, and then pembrolizumab vs EXTREME in the total population.
The final analysis included data from 882 patients with incurable recurrent/metastatic head and neck squamous cell carcinoma who were tested for PD-L1, and randomized to pembrolizumab, 200 mg on day 1 of each week in 3-week cycles for up to 24 months (n = 301), pembrolizumab for up to 24 months plus 6 cycles of chemotherapy (cisplatin, 100 mg/m2 or carboplatin AUC 5 in 3-week cycles and fluorouracil 1,000 mg/m2/day for 4 days in 3-week cycles; n = 281), or the standard EXTREME regimen (cetuximab, 400 mg/m2 loading/250 mg/m2 once weekly and 6 cycles of chemotherapy; n = 300).
Patients with CPS ≥ 20 in the pembrolizumab plus chemotherapy arm had significantly improved OS (median, 14.7 months) compared with those in the EXTREME arm (median, 11.0 months; hazard ratio [HR], 0.60; 95% CI, 0.45–0.82; P = .0004); similar results were seen for patients with CPS ≥ 1 in the pembrolizumab plus chemotherapy arm (median, 13.6 months) vs the EXTREME arm (median, 10.4 months; HR, 0.65; 95% CI, 0.53–0.80; P < .0001). Pembrolizumab alone did not significantly improve OS in the total population compared with the EXTRME therapy (median, 11.5 vs 10.7 months; HR, 0.83; 95% CI, 0.70–0.99; P = .0199).
“There have been very few advances in head and neck care for the last 15 years, and this is the first really good evidence that for the first-line setting for patients whose cancer has spread to other parts of the body that immunotherapy is as good as chemotherapy is. So, it really changes how we are looking at these patients and the options that these patients have available to them,” said Randall Kimple, MD, PhD, of the University of Wisconsin-Madison, who specializes in head and neck cancers, in an interview with Cancer Network.
For PFS, the difference between the pembrolizumab plus chemotherapy and EXTREME arms with CPS ≥ 20 (median, 5.8 months vs 5.2 months, respectively; HR, 0.73; 95% CI, 0.55–0.97; P = .0162) was not significant (superiority threshold of P = .0017). For the CPS ≥ 1 comparison, there was also no significant difference (median, 5.0 months for both; HR, 0.82; 95% CI, 0.67–1.00).
All-cause grade 3–5 adverse event rates were 85.1% for pembrolizumab plus chemotherapy, and 83.3% for the EXTREME therapy. Immune-related adverse event rates were 4.7% and 8.4%, respectively.
“For our patients who have had very little hope for a long time because there weren’t great treatments, this is starting to move the bar. Patients now have options where they didn’t really have options before,” noted Kimple.