1.34 mg of Fotivda offered decreased tumor dimension and could also be extra tolerable than an 0.89-mg dose in RCC: © Axel Kock – inventory.adobe.com
Amongst sufferers with renal cell carcinoma (RCC), the Meals and Drug Administration (FDA)-approved beginning dose of 1.34 milligrams (mg) of Fotivda (tivozanib) resulted in better antitumor exercise than a diminished dose of 0.89 mg, whereas incidence of hypertension have been seen to be comparable.
Glossary
Development-free survival: The time a affected person lives with out their illness spreading or worsening.
Greatest total response: One of the best response a affected person has to therapy.
Total survival: The time a affected person lives, no matter illness standing.
This was in accordance with outcomes from an built-in efficacy and security publicity response evaluation that included the part 3 TIVO-1, TiNivo-2 and TIVO-3 research offered on the 2025 ASCO Genitourinary Cancers Symposium.
“[There was a] robust publicity response relationship between cycle 2 [Fotivda] serum [exposures] and progression-free survival [PFS],” Dr. Bradley McGregor, lead examine creator, wrote in a poster presentation of the information. McGregor is director of Scientific Analysis for the Lank Middle of Genitourinary Oncology, a senior doctor in addition to Marra Lochiatto Investigator at Dana-Farber Most cancers Institute, and an assistant professor of medication at Harvard Medical Faculty, all in Boston.
When PFS was stratified by Fotivda cycle 2 exposures quartile, knowledge confirmed that those that obtained a better focus of Fotivda had the longest median PFS of sufferers examined. Sufferers with an publicity starting from 62 to 177 ng/mL had the longest median PFS at 9.7 months and the median PFS was as follows for these with an publicity starting from 47.9 to 62.0 ng/mL (median PFS, 9.1 months), 38.4 to 47.9 ng/mL (median PFS, 7.3 months) and 13.9 to 38.4 ng/mL (median PFS, 5.6 months).
“A correlation between [Fotivda exposures] and alter in tumor dimension from baseline was additionally noticed,” McGregor wrote. “Sufferers within the TiNivo-2 mixture remedy arm who obtained 0.89 mg [of Fotivda] are largely clustered within the lowest [Fotivda exposure] quartile. As [exposure] quartiles of [Fotivda] enhance, sufferers’ tumor dimension decreases, indicating [a] greater [Fotivda dose] leads to an elevated tumor response.”
The Fotivda publicity quartile correlations with adjustments in tumor dimension and finest total response (BOR) within the tumor dimension mannequin revealed the next adjustments in median BOR for these with an publicity starting from: 62 to 177 ng/mL (median BOR, –23.8), 47.9 to 62 ng/mL (median BOR, –17.3), 38.4 to 47.9 ng/mL (median BOR, –11.7) and 13.9 to 38.4 ng/mL (median BOR, –7.02). The respective teams included 183, 185, 173 and 176 sufferers.
In TiNivo-2, the decrease dose of Fotivda was given together with Opdivo (nivolumab), and modeling knowledge additionally confirmed that Opdivo didn’t have an effect on the pharmacokinetics of Fotivda. Moreover, the incidence of any grade or grade 3 (extreme) hypertension was not considerably totally different between sufferers who obtained the 2 doses of Fotivda.
Knowledge Resulting in This Publicity Response Evaluation
Beforehand, Fotivda monotherapy was permitted by the FDA in March 2021 for the therapy of adults with relapsed or refractory superior RCC following two or extra prior systemic therapies based mostly on knowledge from TIVO-3. Knowledge from the trial confirmed that the VEGFR TKI elicited a median total survival (OS) of 16.4 months in sufferers (175 sufferers) versus 19.2 months in sufferers who obtained Nexavar (sorafenib, 175 sufferers). The median PFS was 5.6 months versus 3.9 months, respectively. The beneficial dose of Fotivda per the prescribing data and FDA approval is 1.34 mg administered as soon as every day with or with out meals for 21 consecutive days each 28 days till illness development or unacceptable toxicity.
Fotivda was given at a decrease dose of 0.89 mg for 21 days in a 28-day cycle in TiNivo-2 when it was mixed with Opdivo, assuming a danger of hypertension. Nevertheless, the lower-dose routine didn’t enhance outcomes when put next with Fotivda monotherapy given on the permitted 1.34-mg monotherapy dose. A worsened pattern for PFS was noticed as sufferers handled with the doublet (171 sufferers) skilled a median PFS of 5.7 months versus 7.4 months with the monotherapy (172 sufferers).
“The outcomes from the TiNivo-2 knowledge set additional confirmed that rechallenge with immunotherapy doesn’t add profit and optimum dosing of [Fotivda] offered the very best scientific profit following development on immunotherapy … [exposure response] fashions present that 1.34 mg [of Fotivda] gives better antitumor exercise than 0.89 mg. The hypertension incidence appears to be comparable, [and] these [exposure response] knowledge counsel {that a} dose of 1.34 mg [of Fotivda] gives a better lower in tumor dimension and perhaps extra tolerable,” McGregor wrote in conclusion.
Reference
“Built-in efficacy and security publicity response (ER) evaluation of tivozanib (TIVO) for the therapy of renal cell most cancers (RCC).” By Dr. Bradley McGregor, et al. Journal of Scientific Oncology.
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