Combined Programmed Death-Ligand 1 and MET Inhibition: Has Papillary Renal Cell Carcinoma MET Its Match?
Mené sur 41 patients atteints d'un carcinome papillaire du rein de stade métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité d'un traitement combinant savolitinib et durvalumab
Papillary renal cell carcinoma (PRC) represents up to 20% of all renal cell carcinoma (RCC) subtypes. Delahunt and Eble first attempted to subclassify PRC into type 1 and 2 on the basis of histologic findings.1 Subsequent analysis by the Cancer Genome Atlas Research Network noted association of type 1 PRC with MET alterations.2 These MET alterations may occur as germline or somatic point mutations in MET, but some sporadic cases of PRC are also characterized by MET copy number amplification and trisomy of chromosome 7 which houses MET. It was later determined that MET may play a role in the pathogenesis of type 2 PRC as well, with MET copy number alterations in as high as 46% in this subtype.3 These data brought MET into focus as a potential therapeutic target across PRC subtypes, particularly as patients with PRC were experiencing disappointing outcomes with some of the same therapies that were active in clear cell RCC. To frame the problem, sunitinib produced zero partial responses and a median progression-free survival (mPFS) of 1.6 months (95% CI, 1.4 to 5.4) in 27 patients with PRC; 13 patients treated with frontline everolimus experienced the same.4,5 The combination of biologic rationale and desperate clinical need cleared the path toward an exploration of MET inhibition in PRC and ultimately the foundation of the practice-influencing CALYPSO presented by Suarez et al
Journal of Clinical Oncology , éditorial en libre accès, 2022