Abstract 672P
Background
Cabozantinib is a tyrosine kinase inhibitor approved in Europe for use in adults with aRCC who have received prior VEGF-targeted therapy, or are treatment naive with intermediate or poor risk. We report interim data on the real-world use of cabozantinib in patients with aRCC who have received prior VEGF-targeted therapy and nivolumab.
Methods
CASSIOPE (NCT03419572) is an ongoing, non-interventional study of cabozantinib in patients with aRCC who have received prior VEGF-targeted therapy; a pre-planned interim analysis was conducted when 50% of patients had completed ≥ 3 months of follow-up. This post-hoc analysis assessed patient characteristics, best overall response (BOR) based on RECIST 1.1, dose modifications and tolerability at 3 months in the patient subgroup who had received prior nivolumab.
Results
CASSIOPE included 337 patients treated with cabozantinib following prior VEGF-therapy. Of all first-line therapies, sunitinib (56.7%) and pazopanib (32.3%) were most common; nivolumab was the most common second-line therapy. In total, 154 (45.7%) patients had received prior nivolumab in any line (median age, 67.5 years; 70.8% male, 87.7% clear-cell histology, 96.1% metastatic disease; 80.8% ECOG PS 0–1). Within this subgroup, 58.4% of patients initiated cabozantinib at 60 mg/day; median daily dose during the study was 40 mg. Dose modifications and safety data are summarized in the table. During the first 3 months, 58 patients in the prior nivolumab subgroup had an evaluable BOR: 39.7% had a partial response, 44.8% stable disease and 12.1% progressive disease (not evaluable for 3.4% of the patients).
Conclusions
This post-hoc analysis of interim CASSIOPE data suggests that cabozantinib, used in routine care, is broadly tolerable and may offer tumour response in patients previously treated with VEGF-targeted therapy and nivolumab. Table: 672P
| Prior nivolumab CASSIOPE subgroup (n = 154) | ||
| Dose modification, n (%) | Any | Due to adverse events |
| Any | 121 (78.6) | 103 (66.9) |
| Reduction | 72 (46.8) | 67 (43.5) |
| Interruption | 84 (54.5) | 72 (46.8) |
| Discontinuation | 40 (26.0) | 22 (14.3) |
| Most common treatment-emergent adverse events of any grade, n (%) | ||
| Any | 146 (94.8) | |
| Diarrhea | 56 (36.4) | |
| Palmar-plantar erythrodysaesthesia syndrome | 39 (25.3) | |
| Asthenia | 35 (22.7) | |
| Nausea | 34 (22.1) | |
| Fatigue | 33 (21.4) | |
| Hypertension | 32 (20.8) | |
| Decreased appetite | 26 (16.9) | |
| Mucosal inflammation | 25 (16.2) | |
| Stomatitis | 23 (14.9) | |
| Deaths, n (%) | ||
| All cause | 17 (11.0) |
Clinical trial identification
NCT03419572.
Editorial acknowledgement
David Gothard of Oxford PharmaGenesis, Oxford, UK, provided medical writing and editorial support, which was sponsored by Ipsen.
Legal entity responsible for the study
Ipsen.
Funding
Ipsen.
Disclosure
G. Procopio: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca. P. Hamberg: Financial Interests, Personal, Advisory Role, Consulting: Astellas; Financial Interests, Personal, Advisory Role, Consulting: MSD; Financial Interests, Personal, Advisory Role, Consulting: Pfizer; Financial Interests, Personal, Advisory Role, Consulting: AstraZeneca; Financial Interests, Personal, Invited Speaker, Consulting: BMS; Financial Interests, Personal, Invited Speaker, Consulting: Ipsen. P. Bigot: Financial Interests, Personal, Advisory Role, Consulting: Ipsen; Financial Interests, Personal, Advisory Role, Consulting: MSD; Financial Interests, Personal, Advisory Role, Consulting: Pfizer; Financial Interests, Personal, Advisory Role, Consulting: BMS. C. Suarez Rodriguez: Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Eusa; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Sanofi-Aventis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Institutional, Speaker’s Bureau: BMS; Financial Interests, Personal, Research Grant: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Pfizer. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Janssen Cilag; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: EusaPharma; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Sponsor/Funding, Travel expenses: BMS; Financial Interests, Personal, Sponsor/Funding, Travel expenses: Pfizer; Financial Interests, Personal, Sponsor/Funding, Travel expenses: Janssen; Financial Interests, Personal, Sponsor/Funding, Travel expenses: Sanofi; Financial Interests, Personal, Sponsor/Funding, Travel expenses: Ipsen; Financial Interests, Personal, Sponsor/Funding, Travel expenses: MSD; Financial Interests, Personal, Sponsor/Funding, Travel expenses: Roche; Financial Interests, Personal, Sponsor/Funding, Travel expenses: Astellas. J. Eymard: Financial Interests, Personal, Advisory Role: Astellas; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Sanofi. C. Masini: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: BMS; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Sponsor/Funding, Travel, accomodations, expenses: BMS; Financial Interests, Personal, Sponsor/Funding, Travel, accomodations, expenses: Ipsen. P. Gajate Borau: Financial Interests, Personal, Advisory Role: Ipsen; Financial Interests, Personal, Speaker’s Bureau: Ipsen; Financial Interests, Personal, Sponsor/Funding, Travel accomodation: Ipsen. P. Dutailly: Financial Interests, Personal, Full or part-time Employment: Ipsen. V. Perrot: Financial Interests, Personal, Full or part-time Employment: Ipsen. M. Staehler: Financial Interests, Personal, Advisory Role, Consulting: Pfizer; Financial Interests, Personal, Advisory Role, Consulting: GSK; Financial Interests, Personal, Advisory Role, Consulting: Novartis; Financial Interests, Personal, Advisory Role, Consulting: Bayer; Financial Interests, Personal, Advisory Role, Consulting: Roche; Financial Interests, Personal, Advisory Role, Consulting: Aveo; Financial Interests, Personal, Advisory Role, Consulting: EusaPharma; Financial Interests, Personal, Advisory Role, Consulting: Astellas; Financial Interests, Personal, Advisory Role, Consulting: Ipsen; Financial Interests, Personal, Advisory Role, Consulting: Exelixis; Financial Interests, Personal, Advisory Role, Consulting: Pelloton; Financial Interests, Personal, Advisory Role, Consulting: EISAI; Financial Interests, Personal, Advisory Role, Consulting: BMS; Financial Interests, Personal, Advisory Role, Consulting: MSD; Financial Interests, Personal, Invited Speaker, Honoraria: Pfizer; Financial Interests, Personal, Invited Speaker, Honoraria: GSK; Financial Interests, Personal, Invited Speaker, Honoraria: AVEO; Financial Interests, Personal, Invited Speaker, Honoraria: Novartis; Financial Interests, Personal, Invited Speaker, Honoraria: Bayer; Financial Interests, Personal, Invited Speaker, Honoraria: EUSAPharma; Financial Interests, Personal, Invited Speaker, Honoraria: Astellas; Financial Interests, Personal, Invited Speaker, Honoraria: Ipsen; Financial Interests, Personal, Invited Speaker, Honoraria: Exelixis; Financial Interests, Personal, Invited Speaker, Honoraria: Pelloton; Financial Interests, Personal, Invited Speaker, Honoraria: Eisai; Financial Interests, Personal, Invited Speaker, Honoraria: BMS; Financial Interests, Personal, Invited Speaker, Honoraria: MSD; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Research Grant: GSK; Financial Interests, Personal and Institutional, Research Grant: AVEO; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Research Grant: Roche/Genetech; Financial Interests, Personal and Institutional, Research Grant: Immatics; Financial Interests, Personal and Institutional, Research Grant: Wilex; Financial Interests, Personal and Institutional, Research Grant: Ipsen; Financial Interests, Personal and Institutional, Research Grant: Exelixis; Financial Interests, Personal and Institutional, Research Grant: Eisai.