Updated NCCN Guidelines Grant Tivozanib Category 1 Status for Pretreated RCC

The Kidney Cancer Treatment guidelines, housed within the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology, have been revised, granting tivozanib (Fotivda) Category 1 status as a subsequent therapy for patients with renal cell carcinoma (RCC) who have received at least 2 prior lines of treatment, according to an announcement from AVEO Oncology.^1,2

On March 10, 2021, the FDA approved tivozanib for the treatment of adult patients with relapsed/refractory advanced RCC following 2 or more prior systemic therapies.³

The approval was based largely on findings from the phase 3 TIVO-3 trial (NCT02627963). Tivozanib demonstrated a significant improvement in progression-free survival (PFS) compared with sorafenib (Nexavar), with similar overall survival (OS), in patients with highly relapsed/refractory metastatic RCC.⁴

The controlled, multicenter, open-label, phase 3 trial randomized 350 patients with highly refractory metastatic RCC who had failed 2 or more prior regimens, including VEGF-TKI treatment, 1:1 to receive oral tivozanib or sorafenib. Crossover between arms was not permitted.

Primary findings from the study demonstrated an increased independent review committee–assessed median PFS for tivozanib compared with sorafenib at 5.6 months vs 3.9 months, respectively (stratified HR, 0.73; 95% CI, 0.56-0.95; P = .016). The final hazard ratio (HR) for OS was 0.97 (95% CI, 0.75-1.24; P = .78).

Findings from an exploratory analysis from the study presented at the 2022 Genitourinary Cancers Symposium demonstrated that the investigator-assessed HR for PFS favored tivozanib compared with sorafenib (HR, 0.624; 95% CI, 0.49-0.79). That result was comparable to the primary IRC-assessed HR for PFS (unstratified HR, 0.672; 95% CI, 0.52-0.87).5

Additionally, landmark long-term PFS rates were significantly higher with tivozanib vs sorafenib, at 12.3% and 2.4%, respectively, at 3 years, and 7.6% and 0%, respectively, at 4 years. Moreover, mature OS data also reflected a nonsignificant trend in continued favor of tivozanib (HR, 0.89; 95% CI, 0.70-1.14).

“Category 1 is the highest Category recommendation offered by NCCN, which is based on strong clinical evidence and perception of the product among the NCCN Panel Members. The NCCN guidelines are recognized and followed by both academic and community oncologists when selecting appropriate therapeutic options for their patients,” Michael Bailey, president and chief executive officer of AVEO, said in a press release. “This year we presented encouraging long-term, PFS and OS follow-up data from the phase 3 TIVO-3 study. These new data demonstrate the durability of FOTIVDA’s anti-tumor activity which has translated into an improving OS hazard ratio.”

References

1. AVEO Oncology announces updated NCCN clinical practice guidelines elevate fotivda (tivozanib) to category 1 treatment for relapsed or refractory advanced (r/r) renal cell carcinoma (rcc) patients. News release. AVEO Oncology. June 21, 2022. Accessed August 9, 2022. https://bit.ly/3d7jRMU
2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Kidney Cancer Version 2.2023 — August 3, 2022. NCCN. Accessed August 9, 2022.
3. AVEO Oncology Announces U.S. FDA Approval of FOTIVDA® (tivozanib) for the Treatment of Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma. AVEO Oncology. News release. March 10, 2021. Accessed August 9, 2022. https://bwnews.pr/3byYtgo
4. Pal SK, Escudier B, Atkins MB, et al. TIVO-3: Final OS analysis of a phase III, randomized, controlled, multicenter, open-label study to compare tivozanib to sorafenib in subjects with metastatic renal cell carcinoma (RCC). J Clin Oncol. 2020;38(suppl 15):5062. doi:10.1200/JCO.2020.38.15_suppl.5062
5. Atkins MB, Verzoni E, Escudier B, et al. Long-term PFS from TIVO-3: Tivozanib (TIVO) versus sorafenib (SOR) in relapsed/refractory (R/R) advanced RCC. J Clin Oncol. 2022;40(suppl 6):362. doi:10.1200/JCO.2022.40.6_suppl.362