KEYTRUDA (pembrolizumab) - Endometrial cancer (EC)

The clinical benefit of KEYTRUDA 25 mg/mL (pembrolizumab) concentrate for solution for infusion is substantial in the MA indication. 

Considering:

• evidence of a superiority in the phase 3 NRG-GY018/KEYNOTE-868 study of pembrolizumab in combination with paclitaxel + carboplatin chemotherapy in the induction phase, followed by maintenance therapy with pembrolizumab in terms of radiological progression-free survival, with:
  • in dMMR patients (interim analysis scheduled in the protocol): HR = 0.34; 95% CI [0.22; 0.53], p < 0.0001). The PFS median was not reached in the group treated with pembrolizumab + chemotherapy, while it was 8.3 months (95% CI [6.5; 12.3]) in the placebo + chemotherapy group.
  • in pMMR patients (interim analysis scheduled in the protocol): HR = 0.57 (95% CI = [0.44; 0.74], p < 0.0001). The progression-free survival median of 13.1 months (95% CI = [10.6; 19.5]) in the pembrolizumab + chemotherapy group and 8.7 months (95% CI = [8.4; 11.0]) in the placebo + chemotherapy group. 

and despite: 

• the absence of an overall survival analysis with management of the alpha risk specifically scheduled in the protocol for dMMR and pMMR patients in the NRG-GY018/ KEYNOTE-868 study (exploratory endpoint);
• an excess toxicity primarily concerning:
  • in dMMR patients: grade ≥ 3 AEs, with 61.7% in the pembrolizumab group and 47.6% in the placebo group, serious AEs (36.4% and 21.0%);
  •  in pMMR patients: grade ≥ 3 AEs, with 57.8% in the pembrolizumab group and 45.6% in the placebo group, serious AEs (33.8% and 18.8%);
• the absence of any formal conclusion that can be drawn on quality of life (exploratory endpoint). 

the Committee deems that KEYTRUDA 25 mg/mL (pembrolizumab) in combination with carboplatin and paclitaxel in the induction phase, followed by maintenance treatment with KEYTRUDA 25 mg/mL (pembrolizumab) as monotherapy provides a minor clinical added value (CAV IV) compared to the carboplatin + paclitaxel combination in the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC).