Dr Beckermann on the Rationale for Evaluating Tivozanib/Nivolumab After IO-Based Therapy in RCC

“There’s always this hope that immuno-oncology [IO] provides durable benefit, but without the data, many practitioners were continuing IO therapy after progression on PD-1–based inhibitor regimens [in patients with locally advanced or metastatic RCC].”

Kathryn E. Beckermann, MD, PhD, an assistant professor in the Department of Medicine in the Division of Hematology and Oncology at Vanderbilt School of Medicine, highlighted the rationale for evaluating tivozanib (Fotivda) plus nivolumab (Opdivo) for the treatment of patients with locally advanced or metastatic renal cell carcinoma (RCC) who had disease progression on 1 or 2 systemic therapies and at least 1 immune checkpoint inhibitor (ICI).

In the RCC treatment landscape, immuno-oncology (IO)–based therapy is often deemed durable; however, the use of IO after disease progression on frontline PD-1 inhibitor–based regimen is continuously utilized without more data, Beckermann began. The phase 3 TiNivo-2 trial (NCT04987203) allowed for the comparison of tivozanib at 0.89 mg plus nivolumab and the control arm of full-dose tivozanib at 1.34 mg, she said.

The FDA approved tivozanib in March 2021 for the treatment of patients with relapsed/refractory advanced RCC following 2 or more prior lines of systemic therapy. The regulatory decision was supported by findings from the randomized phase 3 TIVO-3 study (NCT02627963).

During TiNivo-2, Beckermann and colleagues also evaluated the patient-reported outcomes (PROs) based on 2 quality of life questionnaires: the Functional Assessment of Cancer Therapy Kidney Cancer Symposium Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. Results demonstrated that PROs in patients treated with tivozanib/nivolumab were similar to those treated with tivozanib monotherapy. Among patients from the intent-to-treat population, the mean FKSI-DRS scores at baseline were 28.8 vs 29.3 in those from the tivozanib/nivolumab and tivozanib monotherapy arms, respectively. At baseline, the mean EORTC QLQ-C30 scores in the respective arms were 63.4 and 66.2. Regarding progression-free survival (PFS) for the combination (n = 111) vs monotherapy (n = 105) in the second line, the median PFS 7.3 months (95% CI, 5.4-9.3) vs 9.2 months (95% CI, 7.4-10.0), respectively (HR, 1.15; 95% CI, 0.82-1.62; P = .4282). In the third-line setting, the median PFS was 4.8 months (95% CI, 3.2-7.5) vs 5.5 months (95% CI, 2.9-7.4), respectively (HR, 0.97; 95% CI, 0.65-1.45; P = .8866).