JEMPERLI (dostarlimab) - Endometrial cancer (EC)

The clinical benefit provided by JEMPERLI 500 mg (dostarlimab) concentrate for solution for infusion is substantial in the MA indication. 

Considering:

• evidence of a superiority in the phase 3 RUBY study of dostarlimab in combination with paclitaxel + carboplatin chemotherapy in the induction phase, followed by maintenance therapy with dostarlimab in terms of radiological progression-free survival, with, in the ITT population, an HR = 0.64 (95% CI = [0.507; 0.800], p < 0.0001 and a PFS median of: 11.8 months [9.6; 17.1] versus 7.9 months [7.6; 9.5] in the comparator group;
  • evidence of a superiority of dostarlimab in combination with paclitaxel + carboplatin chemotherapy in the induction phase, followed by maintenance therapy with dostarlimab, in terms of overall survival, in the ITT population (including 76% pMMR/MSS patients) via an interim analysis; 

but taking into account: 

•  the lack of management of the error risk for analysis of progression-free survival and overall survival for the subgroup of pMMR/MSS patients, who nonetheless represented 76% of the patients included in the RUBY study, making these results exploratory;
•  the existence of a significant quantitative interaction for MMR status concerning the endpoints (PFS and OS) suggesting a lesser effect of dostarlimab in patients with a pMMR tumour status than in those with a dMMR tumour status;
•  an excess toxicity primarily concerning grade ≥ 3 adverse events, with 72.2% in the dostarlimab group versus 60.2% in the placebo group, immunological AEs (58.5% and 37.0%), and serious AEs (39.8% and 28.0%);
• the absence of any formal conclusion that can be drawn on quality of life (exploratory endpoint).

the Committee deems that JEMPERLI 500 mg (dostarlimab) in combination with carboplatin and paclitaxel in the induction phase, followed by maintenance treatment with JEMPERLI (dostarlimab) as monotherapy provides no clinical added value (CAV V) compared to the carboplatin + paclitaxel combination in the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC) with a pMMR/MSS tumour status or in whom the status with respect to this deficiency is not known.