Adding Fotivda (tivozanib) to Opdivo (nivolumab) was shown to have comparable patient-reported outcomes (PROs) versus Fotivda monotherapy for the treatment of locally advanced or metastatic clear cell renal cell carcinoma (RCC) whose disease progressed on one or two systemic therapies and at least one immune checkpoint inhibitor (ICI), according to results from the phase 3 TiNivo-2 study.
Data on PROs, which were presented at the 2025 Genitourinary Cancers Symposium, demonstrated that Fotivda maintained the mean scores for the Functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease-Related Symptoms (FKSI-DRS) and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires.
In the intent-to-treat (ITT) populations from the Fotivda/Opdivo versus Fotivda monotherapy arms, respectively, the mean FKSI-DRS scores at baseline were 28.8 versus 29.3; at week 24, these scores were 29.9 versus 29.4. The mean EORTC QLQ-C30 scores at baseline were 63.4 versus 66.2 in the combination versus monotherapy arms, respectively; at week 24, these mean scores were 68.7 versus 64.8. Patients treated with the combination versus monotherapy in the second line had mean FKSI-DRS scores at baseline of 29.5 versus 29.1; at week 24, these mean scores were 30.1 versus 29.3. Mean EORTC QLQ-C30 scores at baseline in the combination versus monotherapy arms in the second line were 65 versus 67.1; these mean scores at week 24 were 68.7 versus 64.6. In the third-line setting, mean FKSI-DRS scores at baseline were 27.6 versus 29.5; these mean scores at week 24 were 29.5 versus 29.6. Mean EORTC QLQ-C30 scores at baseline in the combination versus monotherapy arms in the third were 60.5 versus 64.9, with mean scores at week 24 of 68.6 versus 65.1.
“In the [Fotivda monotherapy] arm, improvement in FKSI-DRS and EORTC QLQ-C30 scores were numerically greater in patients receiving second-line treatment than third-line treatment, while … fewer patients reported deterioration in the second line than in the third line,” lead study author Dr. Kathryn Beckermann and coauthors wrote in a poster presented at the meeting.
Beckermann is an assistant professor in the Department of Medicine, Division of Hematology and Oncology at Vanderbilt School of Medicine in Nashville, Tennessee.
Fotivda Background and TiNivo-2 Design
The TiNivo-2 study compared Fotivda/Opdivo with Fotivda monotherapy in patients with locally advanced or metastatic clear cell RCC following progression on one or two systemic therapies and at least one ICI. The trial enrolled patients who had radiographic progression during or after at least six weeks of treatment with an ICI in the first or second line; recovered from side effects of previous therapies to grade 1 or baseline; had confirmed clear cell RCC; measurable disease; and an ECOG performance status of 0 or 1.
Eligible patients were randomly assigned to receive Fotivda/Opdivo (171 patients) or Fotivda monotherapy (172 patients). Cycles were 28 days, and treatment was continued until progression or unacceptable toxicity. All patients discontinued Opdivo after two years of treatment.
Researchers has several outcomes of interest including progression-free survival (PFS), overall survival objective response rate and duration of response. An exploratory area of interest was quality of life (QOL).
Additional PROs and Efficacy Data
The FKSI-DRS and EORTC QLQ-C30 summary scores showed that there was not a significant change in symptom scores over time in the combination and monotherapy arms. Specifically in the second and third line, patients from both arms also demonstrated a similar trend in FKSI-DRS and EORTC QLQ-C30 summary scores, with maintained symptom scores over time.
Regarding QOL scores, FKSI-DRS and EORTC QLQ-C30 questionnaires reported consistent trends and proportions of patients with improved (increases in scores of at least 3 points at any point during the study), stable (a change in score of 3 or fewer points confirmed at the next consecutive visit), or deteriorated symptoms (decrease in score of at least 3 points at any point during the study). Based on the FKSI-DRS questionnaire, patients from the combination versus monotherapy arms, respectively, had improved (28.2% versus 22.9%), stable (47.2% versus 53.5%), and deteriorated symptoms (24.6% versus 23.6%). The EORTC QLQ-C30 questionnaire among patients in the combination versus monotherapy arms, respectively, revealed improved (27.7% versus 21.3%), stable (48.9% versus 53.7%), and deteriorated symptoms (23.4% versus 25%).
“Approximately 75% of all patients reported improved or stable kidney cancer and cancer-treatment related symptoms in both treatment arms,” the study authors wrote in the poster.
In patients treated with the combination versus monotherapy in the second line, respectively, FKSI-DRS reflected improved (28% versus 27.5%), stable (52.7% versus 53.8%), and deteriorated (19.4% versus 18.7%) health-related QOL (HRQOL) scores. In the third line, patients in the combination versus monotherapy arms, respectively, had improved (28.6% versus 15.1%), stable (36.7% versus 52.8%), and deteriorated (34.7% versus 32.1%) HRQOL scores. Based on EORTC QLQ-C30, patients from the combination versus monotherapy arms, respectively, treated in the second line had improved (27.8% versus 23%), stable (52.2% versus 56.3%), and deteriorated (20% versus 20.7%) HRQOL scores. Patients treated with the combination versus monotherapy in the third line, respectively, showed improved (27.7% versus 18.4%), stable (42.6% versus 49%) and deteriorated (29.8% versus 32.7%) HRQOL scores.
The rate of PFS events that occurred in patients treated in the combination (111 patients) versus monotherapy (105 patients) arms, respectively, in the second line, was 64% versus 61%; median PFS was 7.3 months versus 9.2 months. Among patients treated with the combination (60 patients) versus monotherapy (67 patients) in the third line, PFS events occurred in 78% versus 72%, respectively; median PFS was 4.8 months versus 5.5 months.
Safety Data
The type and frequency of safety events in the Fotivda monotherapy arm were consistent with the known safety profile of Fotivda, confirming its tolerability.
Treatment-emergent side effects that occurred in 15% or more of patients in the combination versus monotherapy arms, respectively, included hypertension (37% versus 40%), fatigue (29% versus 40%), diarrhea (30% versus 36%), nausea (16% versus 28%), decreased appetite (22% versus 27%), vomiting (12% versus 21%), weakness (23% versus 21%), proteinuria (10% versus 18%), constipation (10% versus 17%), joint pain (16% versus 16%), cough (16% versus 15%), hypothyroidism (9% versus 15%), anemia (17% versus 9%) and itching (16% versus 6%).
“For certain [treatment-emergent side effects], such as fatigue, nausea, vomiting, proteinuria, and hypothyroidism, the combination group showed lower numerical rates,” the study authors wrote. “However, this was not the case for anemia [or] pruritus, which showed the reverse. The lower dose in the combination [group] potentially explains the lower rate of [treatment-emergent side effects] associated with VEGF [tyrosine kinase inhibitors].”
Reference
"Patient-reported outcomes (PROs) for tivozanib (TIVO) + nivolumab (NIVO) vs TIVO monotherapy in patients with renal cell carcinoma (RCC) following an immune checkpoint inhibitor (ICI): results of the phase 3 TiNivo-2 study" by Dr. Kathryn Beckermann, et al., Journal of Clinical Oncology.
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