Response to systemic therapy in fumarate hydratase–deficient renal cell carcinoma

Fumarate hydratase-deficient renal cell carcinoma in extended remission with bevacizumab and erlotinib

“…The AVATAR trial, a phase II prospective study by Srinivasan et al [ 14 ], showed that the combination of bevacizumab and erlotinib is used to reduce glucose delivery to tumour cells and is well tolerated in patients with FH-deficient tumours with an overall response rate (ORR) of 51% and median progression free survival (PFS) of 14.2 months among all patients. Another retrospective study by Carril-Ajuria et al [ 15 ] suggested that anti-angiogenic agents were superior to immune checkpoint inhibitors and mammalian target of rapamycin (mTOR) inhibitors in FH-def RCC. Various treatment-related adverse events associated with this combination are acneiform rash, diarrhoea and skin dryness.…”

Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma

“…Since ICIs failed to induce satisfactory response rates, they should only be offered to patients with a PD-L1 positive tumor (42,43). Dual inhibition of mTOR and VEGF was reported with ORR rates of up to 44%, whereas patients treated with mTOR inhibition alone showed no response (43,44). TKIs were superior to mTOR inhibitors or ICIs alone, presenting with an ORR of up to 64% and a time to progression of 11.6 months (44).…”

“…Dual inhibition of mTOR and VEGF was reported with ORR rates of up to 44%, whereas patients treated with mTOR inhibition alone showed no response (43,44). TKIs were superior to mTOR inhibitors or ICIs alone, presenting with an ORR of up to 64% and a time to progression of 11.6 months (44). Cabozantinib, which is approved for metastatic RCC, might be the preferred TKI in HLRCC (45).…”

Response to the Letter to the Editor Entitled “Do We Have Sufficient Evidence to Define Prognosis for ‘Low-grade’ Fumarate Hydratase-deficient Renal Cell Carcinoma?”

“…This label allows for (1) their precise separation from morphologic mimics including SDH-deficient RCC and other low risk oncocytic tumors, allowing for appropriate referral for genetic counseling; (2) their distinction from the more common high-grade pattern of FH-deficient RCC, which is associated more consistently with disease progression; and (3) consideration on an individual case level, for organ confined tumors, of the possibility of more conservative management along with continued active surveillance. In the end, we all herald the arrival of emerging therapeutic options [6][7][8][9] for the aggressive tumors in the rare FHdeficient spectrum, and we look to greater interinstitutional experience to lend prognostic precision to the even rarer oncocytic patterns.…”