Abstract
Real-world outcomes among patients with advanced/metastatic renal cell carcinoma (mRCC) treated with cabozantinib or other tyrosine kinase inhibitors (TKIs) after checkpoint inhibitor (CPI) therapy.
Author
person
Daniel Yick Chin Heng
University of Calgary, Calgary, AB, Canada
info_outline
Daniel Yick Chin Heng, Gury K. Doshi, Pascale Dutailly, Aude Houchard, Mickael Lothgren, Alisha Monnette, Yunfei Wang, Valérie Perrot, Aly-Khan A. Lalani
Full text
Authors
person
Daniel Yick Chin Heng
University of Calgary, Calgary, AB, Canada
info_outline
Daniel Yick Chin Heng, Gury K. Doshi, Pascale Dutailly, Aude Houchard, Mickael Lothgren, Alisha Monnette, Yunfei Wang, Valérie Perrot, Aly-Khan A. Lalani
Organizations
University of Calgary, Calgary, AB, Canada, Texas Oncology PA, Houston, TX, Ipsen, Paris, France, Ontada, The Woodlands, TX, McMaster University, Hamilton, ON, Canada
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Ipsen
Background:
CPI-based therapy is the first-line standard of care for patients with mRCC, but effectiveness data for subsequent targeted therapies are limited. Cabozantinib, a multi-targeted TKI, is indicated for patients with mRCC in the USA and may be prescribed after doublet CPI therapy.
Methods:
Retrospective study of cabozantinib vs other TKI treatment after CPI therapy for mRCC using the US Oncology Network electronic health record database and chart review. Patients initiated TKI therapy between May 1, 2016 and Nov 30, 2021, immediately after CPI therapy. The primary endpoint was real-world response rate over the first 6 months of treatment (rwRR
6months
) based on physician assessment (complete response (CR): documented CR/indication of remission/disappearance of all lesions/no evidence of disease, or partial response (PR): documented PR/improved disease/responding disease). Covariates were adjusted by inverse probability of treatment weighting. Noninferiority was assessed using a 90% confidence interval (CI) and 10% noninferiority margin; if noninferiority was met, superiority was evaluated using a 95% CI and chi-square test.
Results:
In total, 485 patients were included. Baseline characteristics were similar for the cabozantinib and other TKIs subgroups, including proportions of patients with ≥ 2 metastatic sites (74.7% vs 68.2%) and metastases in bone (45.0% vs 43.5%), brain (8.8% vs 7.1%), liver (18.1% vs 19.5%), lung (35.0% vs 44.2%) and lymph nodes (38.7% vs 31.8%). At 6 months, tumor assessment data were available for 75.5% of patients (cabozantinib, 79.8% of cabozantinib and 66.2% of other TKIs, 66.2%) patients. Adjusted rwRR
6months
was 62.5% for cabozantinib and 46.0% for other TKIs (rate difference: noninferiority, 16.5% [90% CI, 9.3–23.7],
p
< 0.0001; superiority, 16.5% [95% CI, 7.8–25.1],
p
= 0.0002).
Conclusions:
In patients with mRCC receiving standard of care treatment in the USA, cabozantinib was effective post-CPI therapy, including in patients without prior TKI therapy. Difference in adjusted rwRR
6months
significantly favored cabozantinib vs other TKIs. These data may inform global jurisdictions that restrict cabozantinib to the post TKI setting.
Cabozantinib
(n = 331)
Other TKIs
(n = 154)
Age, median (95% CI) yrs
66.6 (65.3–67.6)
68.6 (66.4–70.8)
Men, %
72.8
75.3
ECOG PS ≥ 2, %
18.1
11.0
IMDC risk: poor / intermediate / favorable / missing, %
13.3 / 31.7 / 4.2 / 50.8
7.8 / 29.2 / 1.9 / 61.0
Prior nephrectomy, %
71.9
70.1
Time from RCC diagnosis to first systemic mRCC therapy, median (95% CI) months
10.0 (5.9–14.8)
5.8 (2.4–13.7)
Treatment line: 2L / 3L / ≥4L, %
32.3 / 46.5 / 21.1
36.4 / 48.1 / 15.6
2L treatment after: ipilimumab + nivolumab / pembrolizumab or nivolumab, %
26.3 / 6.0
24.7 / 11.7
Follow-up from TKI initiation, median (95% CI) months
13.2 (11.4–15.2)
12.4 (10.2–16.7)
5 organizations
4 drugs
3 targets
Organization
University of CalgaryOrganization
Texas Oncology PAOrganization
IpsenOrganization
OntadaOrganization
McMaster University and Juravinski Cancer CentreDrug
cabozantinibDrug
ipilimumabDrug
nivolumabDrug
pembrolizumabTarget
PD-1Target
ipilimumabTarget
cabozantinib