Trials Elucidate Benefit of VEGF/IO in Refractory Renal Cell Carcinoma

Tian Zhang, MD, MHS, suggests that certain VEGF inhibitor/immunotherapy combinations hold promise in refractory metastatic kidney cancer, as is the case for patients treated with lenvatinib (Lenvima) and pembrolizumab (Keytruda).

During the 2023 Genitourinary Cancers Symposium, CancerNetwork^® spoke with Zhang, an associate professor in the Department of Medicine at Harold C. Simmons Comprehensive Cancer Center of the University of Texas Southwestern Medical Center, regarding established VEGF and immunotherapy regimens, as well as early data from several phase 1/2 trials in patients with refractory kidney cancer.

Transcript:

Because VEGF and immunotherapy combinations have been used in the first-line settings, we’re also interested in seeing if they have good activity in the refractory setting for metastatic kidney cancer. Of these [trials], the first one that has been published and presented is the phase 2 KEYNOTE-146 trial [NCT02501096], taking patients who had prior immunotherapy-treated metastatic renal cell carcinoma and treating [them] in a single cohort of lenvatinib and pembrolizumab.

The primary end point of that trial was objective response rate, and in the immunotherapy-pretreated population of over 100 patients, [approximately] 63% had partial responses and then about 30% had stable disease.¹

The vast majority of patients had some stability of their disease or better. [Lenvatinib plus pembrolizumab] is one of our options now in the refractory setting if patients are progressing slowly on first-line immunotherapy combinations, and they have not had access to lenvatinib.

We’ve also seen early phase studies using both cabozantinib [Cabometyx] with atezolizumab [Tecentriq] in the phase 1/2 basket trial, COSMIC-021 [NCT03170960], with an objective response rate of 58% [with 60 mg of cabozantinib].² This is driving the phase 3 CONTACT-03 trial [NCT04338269], which is [randomly assigning] patients to cabozantinib with atezolizumab vs cabozantinib. That trial is still pending report.

Finally, [there is the] combination of tivozanib [Fotivda] with nivolumab [Opdivo] in which the [phase 1/2 TiNivo] study [NCT03136627] showed a median progression-free survival of about 19 months and a 62% partial response rate [for those who were previously treated].³ Based on that, there’s also a phase 3 trial called TiNivo-2 [NCT04987203]. This is a trial combining tivozanib with nivolumab and comparing [them] against tivozanib [monotherapy] in the refractory setting.

All of these trials will give us more information about the combination VEGF and immunotherapy options in the refractory setting.

References

1. Lee C, Shah AY, Rasco D, et al. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study. Lancet Oncol. 2021;22(7):P946-958. doi:10.1016/S1470-2045(21)00241-2
2. Pal SK, McGregor B, Suárez C, et al. Cabozantinib in combination with atezolizumab for advanced renal cell carcinoma: results from the COSMIC-021 study. J Clin Oncol. 2021;39(33):3725-3736. doi:10.1200/JCO.21.00939
3. L Albiges, P Barthelemy, M Gross-Goupil, S Negrier, MN Neddle, B Escudier. TiNivo: safety and efficacy of tivozanib-nivolumab combination therapy in patients with metastatic renal cell carcinoma. TiNivo: safety and efficacy of tivozanib-nivolumab combination therapy in patients with metastatic renal cell carcinoma. Ann Oncol. 2021;32(1):97-102. doi:10.1016/j.annonc.2020.09.021