Final Analysis of a Noninterventional Study on Cabozantinib in Patients With Advanced Renal Cell Carcinoma After Prior Checkpoint Inhibitor Therapy of the German Interdisciplinary Working Group on Renal Tumors (IAG-N).

Background: Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC).
Objective: To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies.
Design, Setting and Participants: Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany.
Interventions: Cabozantinib was administered as a standard of care.
Outcome Measurements and Statistical Analysis: Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized.
Results and Limitations: About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study.
Conclusions: Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.
Competing Interests: Disclosure VG: Compensated lectures: AstraZeneca, Astellas, BMS, EISAI, Ipsen, Janssen-Cilag, Merck, MSD, Pfizer, ONO Pharmaceutical, Novartis/AAA. Advisory Board: Apogepha, BMS; EISAI, EUSA Pharm, Cureteq, Debiopharm, Gilead, Janssen-Cilag, Merck, MSD, Pfizer, Novartis, Oncorena, PCI Biotech. Research Grant: AstraZeneca, BMS, MSD, Ipsen, Pfizer. Travel support: AstraZeneca, Ipsen, Merck, Janssen, Pfizer MB: RR: Advisory Board: Apogepha,Ipsen, Merck .Pfizer Travel support: Janssen, Pfizer GN: compensated lectures: Roche Pharma, MEDAC, Pfizer, BMS, AstraZeneca, Merck, Janssen-Cilag, Astellas; Advisory Boards: Roche Pharma, Sanofi, BMS, Merck Serono, Pfizer, MEDAC, Ipsen, Janssen, Travel support:Roche Pharma, Pfizer, Merck, Janssen, maunscript writing: Pfizer, BMS, Merck MJS: Compensated lectures: Astellas, Apogepha, Bayer, BMS, EISAI, Hexal, Ipsen, Merck, Pfizer, Medac, MSD, Janssen-Cilag. Advisory board: BMS, Gilead, Ipsen, Merck, Novartis, Pfizer, MSD, Janssen-Cilag. Congress: Apogepha, Janssen-Cilag, Ipsen, Pfizer. Research Grants: Gilead, Ipsen, Janssen-Cilag, AstraZeneca, QED, MSD. FA: none, MM: none, MC: none, MOZ: none AW: Compensated lectures: AIO, BMS, Gilead, Janssen, Lilly, iOMEDICO Advisory Board: BMS;Gilead, Lilly Merck, MSD, Pfizer,Janssen Research Grant: AIO, iOMEDICO AH: none JC: none CD: Compensated lectures from Janssen-Cilag, Ipsen. Advisory Board: Janssen-Cilag, Ipsen. Travel support: Janssen-Cilag, Ipsen and Bayer HT: none, MS: none, DS: none PI: Compensated lectures: AstraZeneca, BMS, EISAI, Merck, MSD, Pfizer, Novartis/AAA. Advisory Board: Apogepha, BMS; EISAI, EUSA Pharm, Gilead, Ipsen, Merck, MSD, Pfizer, Novartis, Oncorena, PCI Biotech. Research Grant: AstraZeneca, BMS, MSD, Ipsen, Pfizer. Travel support: AstraZeneca, Ipsen, Merck, Pfizer
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