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FDA Approves Belzutifan for Advanced Renal Cell Carcinoma

The FDA has approved belzutifan (Welireg) for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior therapy with a PD-1/PD-L1 inhibitor and a VEGF-TKI[1][2][4][5]. This approval provides a new targeted therapy option for patients with relapsed or refractory RCC, a population with significant unmet medical need.

Belzutifan is an oral hypoxia-inducible factor (HIF)-2α inhibitor that selectively blocks the HIF-2α transcription factor, a key driver of tumor growth and angiogenesis in clear cell RCC[1][3]. The approval was based on results from the phase 3 LITESPARK-005 trial, in which belzutifan demonstrated a statistically significant improvement in progression-free survival (PFS) compared to everolimus[1][2][4][5]. While median PFS was similar between the two arms at 5.6 months, belzutifan reduced the risk of disease progression or death by 25%[1][4][5].

Belzutifan also showed an objective response rate of 22%, with a complete response rate of 3% and a partial response rate of 19%[2][4]. In contrast, the ORR for everolimus was only 4%, all partial responses[4]. A descriptive analysis of patient-reported outcomes suggested that belzutifan was associated with less worsening of disease-related symptoms and better preservation of health-related quality of life compared to everolimus[5].

The most common adverse reactions (≥25% incidence) with belzutifan were decreased hemoglobin, fatigue, musculoskeletal pain, increased creatinine, and liver enzyme abnormalities[3][5]. Serious adverse events occurred in 38% of patients, including hypoxia, anemia, pneumonia, hemorrhage, and pleural effusion[2][4]. Fatal adverse events were reported in 3.2% of patients, and 6% discontinued treatment due to adverse events[4].

In summary, the FDA approval of belzutifan represents an important advancement in the treatment of advanced RCC. By targeting a novel molecular pathway and demonstrating improved PFS and response rates compared to an approved standard of care, belzutifan provides a much-needed new therapeutic option for patients with relapsed or refractory disease. As the oncology field continues to evolve, targeted therapies like belzutifan will play an increasingly central role in improving outcomes for patients with this challenging malignancy.