A Breakthrough From China in a Rare Form of Kidney Cancer
Mené sur 41 patients atteints d'un carcinome rénal de stade avancé avec déficience en fumarate hydratase (âge médian : 36 ans), cet essai non randomisé de phase II évalue l'efficacité, du point de vue du taux de réponse objective et de la survie sans progression, et la toxicité du sintilimab en combinaison avec l'axitinib
The study published in JAMA Oncology by Zhang et al describes the first, to our knowledge, prospective clinical trial dedicated to patients with documented fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) and treated with a combination of a programmed cell death 1 protein (PD-1) inhibitor (sintilimab) and a vascular endothelial growth factor receptor–targeted tyrosine kinase inhibitor (VEGFR-TKI; axitinib). This open-label phase 2 study, in which 41 patients with genetically and pathologically confirmed FH-deficient RCC were treated with sintilimab, 300 mg, intravenously every 3 weeks and axitinib, 5 mg, orally twice daily revealed an objective response rate of 56% with a median progression-free survival of 19.8 months, rejecting the prespecified null hypotheses. From a safety perspective, the regimen was well tolerated with only 1 patient stopping therapy for treatment-emergent adverse events, while the most common toxicities were mostly asymptomatic and low grade, including proteinuria (63%), hypertriglyceridemia (58%), and hypothyroidism (52%). Fifteen patients (37%) required immunosuppressive agents for immune-related adverse events, mostly grade 1 to 2 rash, and 21% of patients underwent a single dose reduction of axitinib, mostly for grade 1 to 2 palmar plantar erythrodysesthesia. For this recently recognized, underdiagnosed distinct pathologic entity, these results set promising new expectations for treatment and outcomes.
JAMA Oncology , commentaire, 2025