Zanidatamab plus tislelizumab en chemotherapie verbetert overleving bij HER2-positief gastro-oesofageaal carcinoom
In een open-label fase 3-randomisatieonderzoek kregen patiënten met onbehandeld, HER2-positief gevorderd gastro-oesofageaal adenocarcinoom zanidatamab plus tislelizumab en chemotherapie, zanidatamab plus chemotherapie of standaard trastuzumab plus chemotherapie.
De progressievrije overleving was significant langer bij beide zanidatamab-armen vergeleken met trastuzumab (HR respectievelijk 0,63 en 0,65; P<0,001), en de totale overleving was langer bij de combinatie met tislelizumab (HR 0,72; P=0,004).
De frequentie van bijwerkingen graad 3 of hoger lag tussen de 74 en 83 procent, met diarree als meest voorkomende ernstige bijwerking. Deze resultaten ondersteunen een nieuwe standaard voor de eerste-lijn behandeling van HER2-positief gastro-oesofageaal kanker, waarbij de toevoeging van tislelizumab een duidelijk overlevingsvoordeel biedt ten opzichte van trastuzumab.
Abstract (original)
BACKGROUND: Zanidatamab, a dual human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody, plus chemotherapy both with and without tislelizumab (anti-programmed death 1), showed encouraging efficacy and safety as first-line therapy in phase 2 studies involving patients with HER2-positive gastroesophageal adenocarcinoma. METHODS: In an open-label, phase 3 trial, we randomly assigned, in a 1:1:1 ratio, patients with previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma to receive zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. The two primary end points were progression-free survival and overall survival. RESULTS: At a median follow-up of 25.9 months, progression-free survival was longer with zanidatamab-tislelizumab-chemotherapy (median among 302 patients, 12.4 months) and zanidatamab-chemotherapy (median among 304 patients, 12.4 months) than with trastuzumab-chemotherapy (median among 308 patients, 8.1 months) (hazard ratio for progression or death with zanidatamab-tislelizumab-chemotherapy, 0.63 [95% confidence interval {CI}, 0.51 to 0.78]; hazard ratio with zanidatamab-chemotherapy, 0.65 [95% CI, 0.52 to 0.81]; P<0.001 for both comparisons). Overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy (median, 26.4 vs. 19.2 months; hazard ratio for death, 0.72; 95% CI, 0.57 to 0.90; P = 0.004). At this interim analysis, overall survival did not differ significantly between zanidatamab-chemotherapy (median, 24.4 months) and trastuzumab-chemotherapy (hazard ratio, 0.80; 95% CI, 0.64 to 1.01; P = 0.06). The incidence of grade 3 or higher adverse events was 83.3% with zanidatamab-tislelizumab-chemotherapy, 73.8% with zanidatamab-chemotherapy, and 74.5% with trastuzumab-chemotherapy; diarrhea was the most common such event, in 24.8%, 20.0%, and 12.9% of patients, respectively. CONCLUSIONS: Zanidatamab plus chemotherapy, both with and without tislelizumab, led to longer progression-free survival than trastuzumab plus chemotherapy among patients with HER2-positive advanced gastroesophageal adenocarcinoma. At this interim analysis, overall survival was longer with zanidatamab-tislelizumab-chemotherapy than with trastuzumab-chemotherapy; further analyses are planned to assess zanidatamab-chemotherapy. Diarrhea was a common adverse event. (Funded by Jazz Pharmaceuticals and others; HERIZON-GEA-01 ClinicalTrials.gov number, NCT05152147.).
Dit artikel is een samenvatting van een publicatie in The New England journal of medicine. Voor het volledige artikel, alle details en referenties verwijzen wij u naar de oorspronkelijke bron.
Lees het volledige artikelDOI: 10.1056/NEJMoa2517729