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Researchers have published findings from the phase 2 LITESPARK-003 study of patients with previously untreated advanced clear-cell renal cell carcinoma.
Among patients with previously untreated advanced clear-cell renal cell carcinoma (ccRCC), first-line treatment with Welireg (belzutifan) in combination with Cabometyx (cabozantinib) was found to elicit promising responses.
Researchers published findings from the phase 2 LITESPARK-003 study in The Lancet Oncology, concluding in their findings that the combination “has promising antitumor activity in treatment-naive patients with clear-cell renal cell carcinoma. Results from this study support further investigation of this regimen, including biomarker analysis to select patients in whom [Welireg] plus [Cabometyx] might be most effective.”
In the ongoing trial, patients received 120 milligrams of Welireg orally once daily and 60 milligrams of Cabometyx once daily until unacceptable side effects, disease progression or patient withdrawal.
Researchers reported that between Sept. 27, 2018 and Jan. 10, 2023 138 patients were screened for eligibility, with 50 enrolled and assigned to the cohort in question. Patients’ median age was 64, 40 (80%) were male and 48 (96%) were White.
Objective response rate: patients who responded partially or completely to treatment.
Complete response: the disappearance of cancer.
Progression-free survival: the time a patient lives without their disease spreading or worsening.
Overall survival: the time a patient lives, regardless of disease status.
At a median follow-up of 24.3 months, 35 patients, or 70%, had demonstrated a confirmed objective response, with four (8%) who experienced a complete response and 31 (62%) who had a partial response.
Additionally, a post-hoc analysis found that 49, or 98% of patients, had disease control, meaning a confirmed best overall response of stable disease or better.
The median time to response was 1.9 months, and as of the data cutoff 24, or 48% of patients, were still under ongoing treatment. The median duration of response was 28.6 months, and the median progression-free survival was 30.3 months. The median overall survival was not reached, but the estimated 12- and 24-month overall survival rates were 96% and 86%. By the time of data cutoff, five, or 10% of patients, had died, researchers reported.
Researchers reported that the most common grade 3 (severe) to 4 (life-threatening) treatment-related side effects were hypertension (12%), anemia (10%) and fatigue (8%). While seven, or 14%, of patients had serious treatment-related side effects, no treatment-related deaths occurred, researchers reported.
Researchers noted that all patients experienced at least one all-cause side effect, with grade 3 to 5 (fatal) events occurring in 30, or 60%, of patients. One patient died from a died from hepatic failure and spontaneous bacterial peritonitis as of the data cutoff, with neither event considered related to study treatment by the investigator, according to the study.
Treatment-related side effects occurred in all patients, with grade 3 treatment-related side effects occurring in 22, or 44% of patients and a grade 4 case of hypertension determined to be related to Cabometyx occurring in one patient.
Side effects led to Welireg dose reductions in 14, or 28% of patients, and interruptions in 24, or 48%, of patients, while they led to Cabometyx dose reductions and interruptions in 37, or 74%, of patients. Side effects led to the discontinuation of Welireg and Cabometyx in five, or 10%, and six or 12%, of patients, respectively.
Reference:
“Belzutifan plus cabozantinib as first-line treatment for patients with advanced clear-cell renal cell carcinoma (LITESPARK-003): an open-label, single-arm, phase 2 study” by Dr. Toni K. Choueiri, et al., The Lancet Oncology.
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