Real-world evidence of cabozantinib in patients with metastatic renal cell carcinoma: Results from the CABOREAL Early Access Program

Abstract

Background: Real-world data on cabozantinib in metastatic renal cell carcinoma (mRCC) is limited. This study (CABOREAL) reports treatment patterns and outcomes for patients treated with cabozantinib through the French Early Access Program. Patients and methods: This multicentre (n Z 26), observational, retrospective study enrolled patients with mRCC who had received 1 dose of cabozantinib. Overall survival (OS) was estimated using the KaplaneMeier method; subgroups were compared using the log-rank test.A multiple Cox regression model assessed predictive factors of OS after cabozantinib initiation. Results: Four hundred and ten recruited patients started treatment between September 2016 and February 2018: the Eastern Cooperative Oncology Group Performance Status 2, 39.3%; poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, 31.7%; 0e1, 2 and 3 previous treatment lines, 25.3%, 33.4% and 41.2%, respectively; bone metastases, 55.9%; brain metastases, 16.8%. Median (minemax) follow-up was 14.4 (0 e30) months. Overall, 57.0% of patients had a dose reduction, 15.6% an alternative dose schedule. The median average daily dose was 40.0 mg. Median (quartile [Q]1eQ3) treatment duration was 7.6 (0.1e29.1) months, median OS was 14.4 months, and the 12-month OS rate was 56.5% (95% confidence interval: 51.5e61.2). Most patients (54.4%) received subsequent treatment. Predictive factors associated with longer OS were body mass index 25 kg/m 2 (p Z 0.0021), prior nephrectomy (p Z 0.0109), favourable or intermediate IMDC risk (p < 0.0001) and cabozantinib initiation at 60 mg/day (p Z 0.0486). Conclusions: In the largest real-world study to date, cabozantinib was effective in unselected, heavily pretreated patients with mRCC. Initiation at 60 mg/day was associated with improved outcomes. ClinicalTrials.gov identifier: NCT03744585.

Real-Word Experience of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis)

“…Nearly all patients (99%) received cabozantinib in the second or laterline setting with 41% of patients having had > 3 lines of prior therapy. Consistent with our results, this study revealed a median treatment duration of 7.6 months and a median OS of 14.4 months [16]. In contrast to our analysis, the CABOREAL study did not report response rates or TTF outcomes.…”

“…We observed activity of cabozantinib in patients who had previously received ICI, with a DCR of 64% and median OS of 15.8 months (range 10.3 -20.7 months). Similar findings were seen in the METEOR study as well as other retrospective series [16][17][18][19][20]. Importantly, we included patients treated immediately after first-line ICI-based combination therapy (Table 3), which represents a group where data is lacking on the optimal treatment strategy.…”

Early Clinical Experience with Cabozantinib for Advanced Renal Cell Carcinoma in the UK: Real-World Treatment Pathways and Clinical Outcomes

“…The CERES population was more similar to that of CABOREAL (NCT03744585) -the largest study of cabozantinib in a real-world RCC population conducted to date. 20 CABOREAL included patients (n = 410) receiving cabozantinib treatment for RCC via the French Temporary Authorisation for Use (ATU) programme. 20 CCI score was not reported in CABOREAL, but 39.3% of included patients had an ECOG PS of at least 2, and approximately one-third of patients were categorized as having poor-risk IMDC (31.7%) and MSKCC (33.9%) scores.…”

“…20 CABOREAL included patients (n = 410) receiving cabozantinib treatment for RCC via the French Temporary Authorisation for Use (ATU) programme. 20 CCI score was not reported in CABOREAL, but 39.3% of included patients had an ECOG PS of at least 2, and approximately one-third of patients were categorized as having poor-risk IMDC (31.7%) and MSKCC (33.9%) scores. 20 Estimated median OS was slightly longer in CABOREAL than in CERES (14.4 versus 10.8 months, respectively), 20 but published real-world estimates for OS vary widely for aRCC populations (7.7-23.7 months) 11,21,22 because of key differences in the design and eligibility for the associated studies.…”

“…20 CCI score was not reported in CABOREAL, but 39.3% of included patients had an ECOG PS of at least 2, and approximately one-third of patients were categorized as having poor-risk IMDC (31.7%) and MSKCC (33.9%) scores. 20 Estimated median OS was slightly longer in CABOREAL than in CERES (14.4 versus 10.8 months, respectively), 20 but published real-world estimates for OS vary widely for aRCC populations (7.7-23.7 months) 11,21,22 because of key differences in the design and eligibility for the associated studies. Similarly, PFS estimates vary considerably within the realworld literature, ranging from 6.7-12.5 months (compared with 6.0 months in CERES).…”