The immune checkpoint inhibitor pembrolizumab (Keytruda, Merck) has been approved by the US Food and Drug Administration for use in first-line treatment of metastatic or unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
The product was already approved for use in the second-line setting for this cancer type, but has now moved to first-line on the basis of results from the pivotal phase 3 KEYNOTE-048 clinical trial.
Final results from this trial were presented recently at the American Society of Clinical Oncology annual meeting, and were described by experts at the meeting as being 'practice-changing,' as reported by Medscape Medical News.
Specifically, pembrolizumab can now be used first-line either as monotherapy in a subgroup of patients with HNSCC whose tumors express program cell death ligand-1 (PD-L1), or in combination with chemotherapy (platinum plus 5-fluorouracil) in all patients with HNSCC, regardless of PD-L1 expression.
In the pivotal trial, both of these treatment options showed an improved overall survival (OS) when compared to the EXTREME regimen (ie, targeted agent cetuximab used with chemotherapy with cisplatin/carboplatin plus 5-fluorouracil), which has been the standard first-line therapy for HNSCC until now.
For the whole patient population, the median OS for pembrolizumab plus chemotherapy was 13 months vs 10.7 months with the EXTREME regimen (hazard ratio [HR] 0.77; 95% CI: 0.63, 0.93; P = .0067), according to the FDA.
In the subgroup of patients with HNSCC tumors showing PD-L1 expression (measured as PD-L1 combined positive score (CPS) ≥ 1 and found in 44% of patients), the median OS was 12.3 months with pembrolizumab monotherapy vs 10.3 months with the EXTREME regimen (HR, 0.78; 95% CI: 0.64, 0.96; P = .0171).
However, pembrolizumab monotherapy was not superior to chemotherapy alone in the overall patient population.
Also, there was no improvement in progression-free survival (PFS) with either pembrolizumab monotherapy or pembrolizumab in combination with chemotherapy when compared with the EXTREME regimen.
"This approval is a very exciting milestone in the treatment of head and neck cancer and has the potential to transform the way we treat patients with this debilitating disease by offering important new therapeutic options," said KEYNOTE-048 investigator Barbara Burtness, MD, professor of medicine at the Yale School of Medicine and codirector of the Development Therapeutics Research Program at Yale Cancer Center in New Haven, Connecticut.
"Metastatic or recurrent head and neck cancer has been an area of significant unmet need, so it is encouraging to have immunotherapy regimens available for patients in the first-line setting," she commented in a press release issued by Merck.
Companion Diagnostic Test
The FDA notes that the subgroup pf patients with PD-L1 CPS≥1 expression can be found using the PD-L1 IHC 22C3 pharmDx kit, and the agency extended the approval for this kit to include its use as a companion diagnostic device for selecting patients with HNSCC for treatment with pembrolizumab as a single agent.
The recommended pembrolizumab dose for HNSCC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression, the agency notes.
The FDA adds that the most common adverse reactions reported in ≥20% of patients who received pembrolizumab as a single agent in KEYNOTE-048 were fatigue, constipation, and rash. The most common adverse reactions reported in ≥20% of patients who received pembrolizumab in combination with chemotherapy in KEYNOTE-048 were nausea, fatigue, constipation, vomiting, mucosal inflammation, diarrhea, decreased appetite, stomatitis, and cough.
KEYNOTE-048 was funded by Merck & Co, manufacturer of pembrolizumab.
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Cite this: Pembro Now Approved for First-Line Use in Head and Neck Cancer - Medscape - Jun 11, 2019.
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