Pembrolizumab plus chemotherapy as first-line treatment for advanced biliary tract cancer
Mené sur 1 069 patients atteints d'un cancer des voies biliaires de stade avancé (durée médiane de suivi : 25,6 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'ajout du pembrolizumab à une chimiothérapie de première ligne combinant gemcitabine et cisplatine
Résumé en anglais
Biliary tract cancers have increased in incidence in many parts of the world, particularly cases of intrahepatic disease. 1 , 2 The incidence of cholangiocarcinoma varies geographically, with 1·6 cases per 100 000 people in the USA, for example, but substantially higher rates in parts of east Asia. 2 Most patients present with advanced disease not amenable to surgery and require systemic therapy. For more than 10 years, gemcitabine and cisplatin was the internationally accepted first-line treatment for patients with locally advanced and metastatic biliary tract cancer, as per the ABC-02 study. 3 Despite doublet chemotherapy, outcomes are poor, with a median overall survival of between 4·6 and 11·7 months according to a systematic review of multiple studies. 4 This therefore represents an area of high unmet need. In 2022, the TOPAZ-1 study showed a significant improvement in median overall survival in patients receiving durvalumab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone (hazard ratio [HR] 0·80 [95% CI 0·66–0·97]; p=0·021). 5 This combination was subsequently approved by the US Food and Drug Administration in September, 2022, providing a new standard of care. Further progress has been made through the use of drugs targeting IDH1, 6 HER2, 7 and FGFR2, 8 but fewer than half of patients have targetable alterations 9 and these therapies are reserved for second-line use in most circumstances.
