This article is more than 5 years old. Information may no longer be current.
Tivozanib shows PFS benefit over sorafenib for advanced kidney cancer
Click Here to Manage Email Alerts
SAN FRANCISCO — Tivozanib induced higher 2-year PFS and objective response rates than sorafenib among patients with refractory metastatic renal cell carcinoma, according to results from the phase 3 randomized, multicenter TIVO-3 study presented at Genitourinary Cancers Symposium.
Tivozanib (Fotivda, AVEO Oncology) — a highly selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor — also appeared better tolerated than sorafenib (Nexavar, Bayer).
However, researchers did not observe an OS benefit at this interim analysis.
“Tivozanib is a potent and selective VEGFR inhibitor and, thus, would be expected to have activity in this setting, as shown in other studies,” Brian I. Rini, MD, professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, staff member of the department of solid tumor oncology at Cleveland Clinic, and a HemOnc Today Editorial Board Member, told HemOnc Today. “Refractory patients in this population need active therapy, especially one with low toxicity.”
In the TIVO-1 trial, researchers observed a median PFS benefit with tivozanib vs. sorafenib among treatment-naive or cytokine-treated patients with metastatic renal cell carcinoma (11.9 months vs. 9.1 months; HR = 0.79; P = .042). However, due to imbalanced crossover to active treatments, OS insignificantly favored sorafenib (28.8 months vs. 29.3 months; HR = 1.25).
the European Medicines Agency,” Rini said during his presentation.
In the refractory setting, researchers of Study 902 observed an 11-month median PFS, 21.4-month median OS, and objective response rate of 18% with tivozanib in the second-line setting of patients with prior VEGFR TKI failure.
In the TIVO-3 trial, Rini and colleagues evaluated data from 350 patients with metastatic renal cell carcinoma who failed two (60%) or three (40%) prior systemic regimens, one of which included a VEGFR TKI other than sorafenib or tivozanib. Twenty-eight percent of patients had prior treatment with a checkpoint inhibitor.
After stratifying patients by International Metastatic RCC Database Consortium (IMDC) risk category and type of prior therapy, researchers randomly assigned patients in a 1:1 ratio to receive 1.5 mg once-daily oral tivozanib for 3 weeks on, 1 week off per cycle (n = 175; median age, 62 years; 72% men) or 400 mg twice daily oral sorafenib continuously in 4-week cycles (n = 175; median age, 64 years; 73% men).
PFS per independent review committee served as the study’s primary endpoint. Secondary endpoints included ORR, OS, duration of response and safety.
At the time of the analysis, 19% of patients assigned tivozanib remained on therapy compared with 5% of patients assigned sorafenib. The primary reasons for treatment discontinuation included disease progression (48% vs. 52%), adverse events (13% vs. 23%), clinical deterioration (11% vs. 8%) or other (8% vs. 9%).
Results showed median PFS of 5.6 months (95% CI, 5.3-7.3) with tivozanib vs. 3.9 months (95% CI, 3.7-5.6) with sorafenib (HR = 0.73; 95% CI, 0.56-0.94).
A greater proportion of patients assigned tivozanib achieved 1-year PFS (28% vs. 11%) and 2-year PFS (18% vs. 5%).
Researchers observed a consistent treatment effect across the patient subgroups; however, there appeared to be a gradient of benefit in terms of IMDC risk category, with greater benefit observed for the favorable- and intermediate-risk categories than for the poor-risk category, Rini said.
Among the subgroup of patients who received previous immunotherapy — a subgroup researcher analyzed separately to reflect practice patterns of using these agents upfront, Rini said — median PFS was 7.3 months (95% CI, 5.3-11.1) with tivozanib vs. 5.1 months (95% CI, 3.6-7.4) with sorafenib (HR = 0.55; 95% CI, 0.32-0.94).
ORR was 18% with tivozanib vs. 8% with sorafenib (P = .02). Median duration of response was not reached (95% CI, 12.9-not estimable) with tivozanib and 5.7 months (95% CI, 5.6-not estimable) with sorafenib.
Interim OS from the first analysis did not show a benefit with tivozanib (median, 16.4 months vs. 19.7 months; HR = 1.12; 95% CI, 0.84-1.51). However, these data are still immature, Rini said.
Any-grade treatment-related adverse events occurred among 84% of the tivozanib group and 94% of the sorafenib group. Fewer patients in the tivozanib group experienced dose reductions (24% vs. 38%) or interruptions (48% vs. 63%) due to adverse events.
More patients assigned tivozanib experienced hypertension (any grade, 36% vs. 25%; grade 3-4, 20% vs. 14%), fatigue (any grade, 29% vs. 19%), dysphonia (any grade, 24% vs. 8%) and hypothyroidism (any grade, 14% vs. 6%), whereas more patients assigned sorafenib experienced diarrhea (any grade, 50% vs. 33%; grade 3-4, 9% vs. 2%), palmar-plantar erythrodysesthesia syndrome (any grade, 38% vs. 16%; grade 3-4, 10% vs. 1%) and rash (any grade, 24% vs. 4%; grade 3-4, 8% vs. 0%).
“Tivozanib is clearly active and well-tolerated, and would also combine well with immuno-oncology agents,” Rini told HemOnc Today. – by Alexandra Todak
Reference:
Rini BI, et al. Abstract 550. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.
Disclosures: AVEO Oncology sponsored this study. Rini reports consultant/advisory roles with Bristol-Myers Squibb, Merck, Novartis, Pfizer, Roche/Genentech and Synthorx; research funding to his institution from AstraZeneca/MedImmune, Bristol-Myers Squibb, Merck, Peloton Therapeutics, Pfizer and Roche/Genentech; and travel expenses from Bristol-Myers Squibb, Merck and Pfizer. Please see the abstract for all other authors’ relevant financial disclosures.