Introduction

Cabozantinib is approved as first-line therapy for patients with intermediate-poor risk metastatic renal cell carcinoma (mRCC); however translating results from pivotal trials to an unselected real-world population remains a concern

Aim

The objective of CabFRONT (Meet-URO 24) study is to report use of front-line Cabozantinib in an unselected real-life population of patients with intermediate-poor mRCC, including non-clear cell histologies.

Patient Profile

Real-life population of treatment-naïve patients with intermediate-poor mRCC treated with cabozantinib.

Methods

CabFRONT is a retrospective observational multicentre Italian Network for Research in Urologic-Oncology (Meet-URO) study

Treatment:

Mrcc patients treated with cabozantinib.

Study Endpoints

Median progression-free survival (mPFS), median overall-survival (mOS), objective response rate (ORR), disease control rate (DCR) & Safety

Results

209 patients were enrolled. Median age was 65 years (36 - 85). 158 patients (76%) started with a dose of 60 mg, while 51 (24%) started with a dose of 40 mg.

140 patients (67%) were classified as intermediate and 69 (33%) as poor risk according to IMDC risk model.

Clear-cell represented the most common histotype (172/209), followed by papillary (19/209), chromophobe (6/209) and NOS (4/209).

Sarcomatoid features were present in 29 patients (14%). Lungs were the most frequent metastatic site, [137 (65%) patients], followed by lymph nodes [115 (55%)], and bones [72 (35%)]. 33 (16%) patients presented brain metastases.

At a follow-up of 23 months (mo), the median progression-free survival (mPFS) was 9.6 mo (95% CI, 7.63-10.9 mo) and the median overall-survival was 21 mo (95% CI, 14-30 mo).

As best overall response, 7 patients achieved a complete response, 73 a partial response and 77 stable disease for an objective response rate (ORR) of 38% and a disease control rate (DCR) of 75%.

ORR for intermediate and poor population was respectively 29% and 10%, DCR was 56% for intermediate risk and 20% for poor risk population. mPFS for intermediate and poor population was respectively 12.73 and 5.27 mo (p < 0.0001).

mPFS for intermediate with 1 risk factor was 17.2 and for intermediate with 2 risk factors was 9.7 mo (p 0.0033).

• Subsequent antineoplastic treatments were received by 41% (86/209) of patients.

Safety

Subsequent nivolumab was received by 87% of patients. 191 patients (91%) reported at least 1 grade (G) 1 to 2 adverse event (AE).

The most common G1 to G2 AEs were fatigue (113 [60%]), mucositis (100 [52%]), hand-foot syndrome (HFS) (91 [47%]), diarrhoea (79 [41%]), hypertension (67 [35%]), and hypothyroidism (60 [31%]).

78 G3 AEs ere reported: the most common were fatigue (19 [24%]) and diarrhoea (18 [23%]).

Permanent discontinuations from the study owing to AEs was observed in 7 patients: three for G3 diarrhea, one of which manifested also G3 renal injury, two for G3 asthenia, one for G3 HFS and one for G3 mucositis.

At least 131 patients (63%) required a dose reduction and 86 (41%) required a transitory interruption to manage toxic effects.

Conclusion

This study confirmed that front-line Cabozantinib is effective and safe in an unselected real-life population of patients with intermediate-poor mRCC, including non-clear cell histologies.

Reference

J Clin Oncol.2023 41:16_suppl, e16539-e16539