Bevacizumab Plus Sunitinib for Patients With Advanced Renal Cell Carcinoma

Adding bevacizumab to the sunitinib on/off regimen for patients with advanced renal cell carcinoma was found to yield significant antitumor activity with a manageable increase in toxicity, according to results from a phase 1/2 trial. While this study was closed early due to a change in standard of care for this patient population, study authors noted certain subgroups that may benefit from the regimen.

Shouki Bazarbashi, MD, King Paisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, and coauthors explained the schedule of sunitinib administration (4 weeks on/2 weeks off), “would allow the use of bevacizumab in the 2-week off period.” Their hypothesis was that toxicity would be lower while efficacy might be increased “due to continued angiogenesis blockade across the whole 6 weeks of the sunitinib cycle.”

In this phase 1/2 trial, 25 patients with locally advanced unresectable or metastatic renal cell carcinoma were enrolled between February 2015 and January 2021. The introduction of checkpoint inhibition to the first-line treatment for patients with renal cell carcinoma caused the early termination of this trial, before full accrual. The phase 1 endpoint was determining the optimal dose of bevacizumab, while the phase 2 endpoint was response rate and progression-free survival. Secondary end points included overall survival rate and safety.

In phase 1, the optimal dose of bevacizumab was determined to be 5 mg/kg. At the data cutoff date there was a median follow-up duration of 42.2 months. The response rate was 52% (1 complete response, 12 partial responses), and 8 patients achieved stable disease for a disease control rate of 84%. The median progression-free survival was 16.5 months, and the median overall survival was 33.3 months.

There were 88% of patients who experienced at least 1 grade 3/4 toxicity. The most common toxicities, occurring in >20% of patients, were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%).

Limitations of the study included being a phase 1/2 trial at a single center that did not meet the planned target of enrollment, and the studied regimen likely benefiting a small population of patients, due to the introduction of frontline checkpoint inhibitors for renal cell carcinoma.

Though the study was terminated early, Dr Bazabashi et al noted, “the trial did meet the primary end point with a response rate greater than 505 and an encouraging progressive disease rate of 12%.” They went on to state that this regimen may benefit patients “in the favorable risk group” and “with intermediate or poor risk and contra-indication for [checkpoint inhibition] therapy or patients at a later line of therapy.”

Source:

Bazarbashi S, Alzahrani A, Aljubran A, et al. Combining sunitinib and bevacizumab for the management of advanced renal cell carcinoma: A phase I/II trial. Oncologist. Published online January 17, 2023. doi:10/1093/oncolo/oyac261