ENHERTU (trastuzumab deruxtecan) - gastric or gastroesophageal junction (GEJ) Adenocarcinoma

The Committee deems that the clinical benefit of ENHERTU (trastuzumab deruxtecan) is substantial “as monotherapy in adult patients with advanced HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received at least two prior trastuzumab-based treatment lines”.

Considering:

• demonstration of a superiority in the phase 2 DESTINY-Gastric01 study of T-DXd treatment compared to treatment of the physician’s choice (TPC) in terms of:
  • ORR (primary endpoint) with a differential of + 37.0% (CI95% = [41.9; 60.5] in the T-DXd group and CI95% = [6.4; 26.2] in the TPC group; p < 0.0001) in favour of T-DXd,
  • OS (ranked secondary endpoint) with a differential of + 4.1 months (HR = 0.59, CI95%: [0.39; 0.88]; p=0.0097) in favour of T-DXd,
• the inadequately met medical need insofar as the efficacy of LONSURF (trifluridine / tipiracil) is limited with short median PFS and OS durations;

and despite:

• the lack of demonstration of any superiority of T-DXd treatment compared to the LONSURF comparator (trifluridine / tipiracil);
• questions concerning the transposability of the results of the DESTINY-Gastric01 study, conducted in Asia only;
• an excess haematotoxicity (neutropenia, anaemia, leukopenia, lymphopenia and thrombocytopenia);
• the risk of diffuse interstitial lung disease/pneumonitis, identified as an important risk in the RMP;
• the absence of a demonstrated impact on quality of life (exploratory endpoint).

the Committee deems that ENHERTU (trastuzumab deruxtecan) provides a minor clinical added value (CAV IV) in the current care pathway as third or later-line treatment, which includes LONSURF (trifluridine / tipiracil).