FDA Approves First-Line Pembrolizumab for Head/Neck Squamous Cell Carcinoma

The US Food and Drug Administration (FDA) recently approved pembrolizumab as a first-line treatment for patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC), according to a press release from the agency.

Pembrolizumab was approved for use with platinum and fluorouracil (FU) for all patients with HNSCC. It was also approved as a single agent in patients whose tumors express PD‑L1 (combined positive score [CPS] ≥ 1) as determined by an FDA‑approved test. The FDA also expanded the intended use for the PD-L1 IHC 22C3 pharmDx kit to include use as a companion diagnostic device for selecting patients with HNSCC for treatment with pembrolizumab as a single agent.

The approval was based on KEYNOTE-04, a randomized, multicenter, open-label trial involving 882 patients with metastatic HNSCC who had not previously received systemic therapy for metastatic disease or with recurrent disease incurable by local therapies.

Patients were randomized to receive one of the following treatments: pembrolizumab as a single agent; pembrolizumab, carboplatin or cisplatin, and FU; or cetuximab, carboplatin or cisplatin, and FU. Randomization was stratified by tumor PD-L1 expression (tumor proportion score [TPS] ≥ 50% or < 50%), HPV status, and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1). PD-L1 expression (TPS and CPS) was determined using the PD-L1 IHC 22C3 pharmDx kit.

A significant improvement in overall survival (OS) was observed in the overall population for patients randomized to pembrolizumab plus chemotherapy compared with cetuximab plus chemotherapy. The median OS was 13.0 months for the pembrolizumab plus chemotherapy arm and 10.7 months for the cetuximab plus chemotherapy arm. Results were similar in the CPS ≥ 20 subgroup and CPS ≥ 1 subgroup.

The trial also demonstrated statistically significant improvements in OS for the subgroups of patients with PD‑L1 CPS ≥ 1 HNSCC and PD-L1 CPS ≥ 20 HNSCC randomized to pembrolizumab as a single agent compared with cetuximab plus chemotherapy. In the CPS ≥ 1 subgroup, the median OS was 12.3 months for the pembrolizumab arm and 10.3 months for the cetuximab plus chemotherapy arm.

For the CPS ≥20 subgroup, the median OS was 14.9 months for the pembrolizumab arm and 10.7 months for the cetuximab plus chemotherapy arm. At the time of the interim analysis, there was no significant difference in OS between the pembrolizumab as a single agent arm and the cetuximab plus chemotherapy arm for the overall population.

There were no significant differences in progression-free survival for either pembrolizumab-containing arm compared with the cetuximab plus chemotherapy arm in any population.

The most common adverse reactions reported in ≥ 20% of patients who received pembrolizumab as a single agent were fatigue, constipation, and rash. The most common adverse reactions reported in ≥ 20% of patients who received pembrolizumab in combination with chemotherapy were nausea, fatigue, constipation, vomiting, mucosal inflammation, diarrhea, decreased appetite, stomatitis, and cough.

According to the FDA, the recommended pembrolizumab dose for HNSCC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity occur, or for up to 24 months in patients without disease progression.