Regulatory Decision Summary for Keytruda

The authorization of Keytruda was based on the results of one multicentre, randomized, open-label phase 3 clinical trial. A total of 882 adult patients who were newly diagnosed with unresectable recurrent or metastatic (R/M) HNSCC that was not previously treated were randomized 1:1:1 to receive Keytruda (pembro mono arm, n = 301), Keytruda in combination with platinum and fluorouracil chemotherapy (pembro combo arm, n = 281) or Cetuximab with platinum and fluorouracil chemotherapy (control arm, n = 300). The median time of exposure to treatment was 3.6, 5.9 and 4.9 months, respectively.

The primary efficacy endpoints were overall survival (OS) and progression-free survival (PFS). The efficacy analyses were conducted in three pre-defined populations, namely, all patients, patients whose tumors had programmed cell death ligand 1 (PD-L1) expression, Combined Positive Score (CPS) ≥1, and CPS ≥20. A substantial improvement in OS was archived in the pembro combo arm in all three populations, and in the pembro mono arm in the two CPS populations. In the pembro combo arm, the risk of death event was reduced by 28% (all patients), 35% (patients with CPS ≥1) and 40% (patients with CPS ≥20), respectively, over the control arm. The median OS (month) was extended by 2.3 (all patients), 3.2 (patients with CPS ≥1) and 3.7 (patients with CPS ≥20), respectively. In the pembro mono arm, the reduction was reported in 26% for patients with CPS ≥1 and 42% for patients with CPS ≥20, and the increase in median OS was 2.0 and 4.1 months, respectively.

Keytruda monotherapy in this HNSCC indication has a favourite safety profile compared to the standard treatment. The safety profile was also consistent with the established safety profile for Keytruda in other indications. When combined with chemotherapy, the safety profile was generally comparable with that in the control arm. The safety findings were consistent with those associated with Keytruda, platinum and fluorouracil. No new safety signals identified. Drug-related adverse events commonly reported were fatigue and hypothyroidism in the pembro mono arm (incidence ≥10%), and anemia, nausea, neutropenia and fatigue in the pembro combo arm (incidence ≥30%), which can be effectively managed by standard clinical practice. Incidences of immune-mediated hypothyroidism and pneumonitis were reported higher in both pembro arms compared to the rates in Keytruda safety reference database.

The efficacy and safety findings in this study settings support a positive risk benefit profile of Keytruda as monotherapy or in combination with platinum and fluorouracil chemotherapy for the first-line treatment of patients with metastatic or unresectable recurrent HNSCC.

The recommended dose of Keytruda for this indication is 200 mg as a fixed dose, given by intravenous infusion once every 3 weeks. View the Keytruda Product Monograph for details.