Combining Sunitinib and Bevacizumab for the Management of Advanced Renal Cell Carcinoma: A Phase I/II Trial

Abstract

Background Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects. Method This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS). Results Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%). Conclusion Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity.

Anti-angiogenic and antitumor effects of anlotinib combined with bevacizumab for colorectal cancer

“…The combination of bevacizumab and cediranib, a VEGFR TKI, has demonstrated potent additive antitumor effects against various advanced solid tumors, indicating that targeting the same angiogenic pathway is not redundant [ 12 , 26 ]. Multiple studies have shown a significant antitumor effect of combining bevacizumab and sunitinib in renal cell carcinoma, with manageable increased toxicity [27] , [28] , [29] , [30] . Consistent with these findings, our study revealed excellent synergistic antitumor activity when combining bevacizumab and anlotinib in CRC.…”

A phase II study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma

“…There have also been studies of alternating TKIs with bevacizumab, a monoclonal antibody that targets VEGF. A phase I/II trial of patients with advanced clear cell RCC tested the standard 4 weeks on, 2 weeks off sunitinib regimen with the addition of bevacizumab on Day 29 of each sunitinib cycle 30 . The rationale behind this treatment regimen was that the 2‐week rest period of standard sunitinib therapy could result in rebound angiogenesis and tumor progression.…”

“…A phase I/II trial of patients with advanced clear cell RCC tested the standard 4 weeks on, 2 weeks off sunitinib regimen with the addition of bevacizumab on Day 29 of each sunitinib cycle. 30 The rationale behind this treatment regimen was that the 2‐week rest period of standard sunitinib therapy could result in rebound angiogenesis and tumor progression. As was the case with our study, this study closed prematurely due to poor accrual but in the 25 patients recruited, a median PFS was reported to be 16.5 months.…”

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects

“…RCCs are generally divided into five subtypes: clear cell, papillary, chromophobe, collecting duct, and unclassified, among which the first three constitute the majority of RCCs ( Truong and Shen, 2011 ). Although advances in the medical and surgical management of RCCs have been made ( Rini et al, 2009 ; Bazarbashi et al, 2023 ), the outcomes associated with the tumor remain relatively poor ( Badran et al, 2020 ). Additionally, differentiating between different subtypes of RCC is still difficult.…”