Sintilimab plus axitinib shows therapeutic potential in FH-deficient RCC

The combination of sintilimab plus axitinib demonstrates encouraging antitumour activity in patients with fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) while having a manageable safety profile, according to a phase II study conducted in China.

The study included 41 treatment-naïve patients (median age 36 years, 24 percent female) with advanced FH-deficient RCC and an ECOG Performance Status of 0 to 2. These patients were treated with sintilimab 200 mg, administered intravenously every 3 weeks, in combination with axitinib 5 mg, taken orally twice daily. Treatment lasted until disease progression, intolerable toxic effects, or withdrawal of consent.

The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). Secondary endpoints included safety, overall survival, disease control rate (proportion of patients with complete or partial response or stable disease for ≥6 months), duration of response, and exploratory genomic-associated outcomes.

Over a median follow-up of 26.0 months, ORR was 56 percent (95 percent confidence interval [CI], 40–72), with the median duration of response not reached (NR, 95 percent CI, 23.3 months to NR). The disease control rate was 73 percent, and the median PFS was 19.8 months (95 percent CI, 10.9 months to NR).

Of note, the subgroup of patients with low somatic copy number alteration burden showed more favourable therapeutic outcomes.

In terms of safety, treatment-related adverse events of grade 3 or higher occurred in 13 patients (32 percent), with the most common being hypertriglyceridemia (7 percent), rash (5 percent), and anaemia (5 percent).