The European Commission has approved cabozantinib (Cabometyx) for previously untreated patients with intermediate- or poor-risk advanced renal cell carcinoma.
Giuseppe Procopio, MD
The European Commission has approved cabozantinib (Cabometyx) for previously untreated patients with intermediate- or poor-risk advanced renal cell carcinoma (RCC), based on a meaningful improvement in progression-free survival (PFS) versus sunitinib (Sutent) in the CABOSUN trial, according to Ipsen, which codevelops the treatment with Exelixis.
In the phase II study, first-line treatment with cabozantinib reduced the risk of progression or death by 52% compared with sunitinib for patients with advanced RCC. The median PFS was 8.6 months with cabozantinib versus 5.3 months for sunitinib (HR, 0.48; 95% CI, 0.31-0.74; P = .0008).
“The value of treatment with Cabometyx has been corroborated by the data generated in clinical trials and since 2016, physicians have also witnessed the potential of it when treating patients following VEGF-targeted therapy. For both of these reasons, physicians will be pleased to soon have access to this new first-line treatment option for intermediate- or poor-risk advanced RCC patients,” Giuseppe Procopio, MD, head of the Genitourinary Unit at Fondazione Istituto Nazionale Tumori Milan, said in a statement.
The CABOSUN trial randomized 157 patients with poor- and intermediate-risk advanced RCC to receive cabozantinib at 60 mg once daily (n = 79) or sunitinib at 50 mg daily for 4 weeks on/2 weeks off (n = 78). Intermediate-risk patients accounted for 81% of the study population. Baseline characteristics were similar between the two arms.
In the cabozantinib group, the median age of patients was 63 years (range, 40-82). Patients had an ECOG performance status of 0 (46%), 1 (42%) and 2 (13%). Thirty-seven percent of patients had bone metastases and 72% had received a prior nephrectomy. The median diameter of lesions was 7.2 cm and the primary metastatic sites were the lung (70%), lymph nodes (57%), and bone (39%). The median number of metastatic sites was ≥3 for 32% of patients.
The objective response rate (all partial responses) with cabozantinib was 20% compared with 9% for sunitinib. When including those with stable disease, the over disease control rate was 75% with cabozantinib versus 47% for sunitinib. A reduction in target lesion size of any magnitude was recorded for 80% of patients in the cabozantinib arm versus 50% with sunitinib.
After 30.8 months of follow-up, the median overall survival was 26.6 months (95% CI, 14.6-not evaluable) in the cabozantinib arm versus 21.2 months (95% CI, 16.3-27.4) in the sunitinib arm, representing a nonstatistically significant 20% reduction in the risk of death (HR, 0.80; 95% CI, 0.53-1.21; P = 0.29).
Cabozantinib showed similar superiority to sunitinib across all prespecified patient subgroups, including risk, bone metastases, and MET status. In those with poor-risk disease, there was a 69% reduction in disease progression or death (HR, 0.31; 95% Ci, 0.11-0.92). In the intermediate group, the HR for PFS was 0.52 in favor of cabozantinib (95% CI, 0.32-0.82).
The median duration of treatment exposure was doubled in the cabozantinib arm (6.5 vs 3.1 months) with fewer dose reductions required with cabozantinib (46% vs 35%). Treatment discontinuation due to adverse events (AEs) was similar between each group (21% vs 22%). Subsequent therapies were similar between each group.
The rate of grade 3/4 AEs was similar between the cabozantinib and sunitinib arms, respectively (68% vs 65%). Grade 5 AEs, regardless of cause, were experienced by 4% of patients in the cabozantinib arm compared with 10% in the sunitinib group.
When compared with cabozantinib, sunitinib led to higher rates thrombocytopenia (61% vs 38%), anemia (46% vs 33%), nausea (39% vs 32%), neutropenia (35% vs 15%), and leukopenia (35% vs 12%). However, compared with sunitinib, cabozantinib was associated with more diarrhea (73% vs 55%), hypertension (67% vs 44%), liver enzyme elevation (AST, 60% vs 31%; ALT, 55% vs 28%), decreased appetite (47% vs 32%) and weight loss (32% vs 17%, dysgeusia (41% vs 29%), and palmar-plantar erythrodysesthesia (42% vs 33%).
Choueiri TK, Hessel C, Halabi S, et al. Progression-free survival (PFS) by independent review and updated overall survival (OS) results from Alliance A031203 trial (CABOSUN): Cabozantinib versus sunitinib as initial targeted therapy doe patients (pts) with metastatic renal cell carcinoma (mRCC). In: Proceedings from the 2017 ESMO Congress; September 8-12, 2017; Madrid, Spain. Abstract LBA38.