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Cabozantinib (Cabometyx) Outperforms Sunitinib (Sutent) in Mid-Stage Kidney Cancer Trial

Company to submit supplemental NDA

Positive results have been reported from a phase 2 study that compared cabozantinib (Cabometyx, Exelixis, Inc.) with sunitinib (Sutent, Pfizer) in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease.

Cabozantinib is an inhibitor of multiple tyrosine kinases, including MET, AXL, and vascular endothelial growth factor (VEGF) receptors, that has shown antitumor activity in more than 20 forms of cancer. In April 2016, the FDA approved cabozantinib tablets for the treatment of patients with advanced RCC who have received prior anti-angiogenic therapy.

The CABOSUN trial was a randomized, open-label, active-controlled study in 157 patients with previously untreated, advanced RCC at intermediate or poor risk, according to Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria. The patients were randomly assigned to receive either cabozantinib (60 mg once daily) or sunitinib (50 mg once daily, four weeks on followed by two weeks off). The study’s primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and the objective response rate (ORR). Eligible patients were required to have locally advanced or metastatic clear-cell RCC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. The trial’s median follow-up period was 22.8 months.

Of the 157 patients enrolled in the study, 81% were intermediate risk; 19% were poor risk; 36% had bone metastases; 46% had an ECOG performance status (PS) of 0; 41% percent had an ECOG PS of 1; and 13% had an ECOG PS of 2. Tumor assessments were performed by the investigators using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. At the time of the analysis of PFS, the median duration of treatment was 6.9 months for cabozantinib and 2.8 months for sunitinib; 13 patients continued on cabozantinib treatment compared with two patients receiving sunitinib treatment. Dose reductions occurred in 58% and 49% of patients, respectively. Discontinuation rates due to an adverse event were 20% for cabozantinib and 21% for sunitinib.

Cabozantinib demonstrated a statistically significant 31% reduction in the rate of disease progression or death compared with sunitinib (hazard ratio [HR], 0.69; one-sided P = 0.012). The median PFS for cabozantinib was 8.2 months compared with 5.6 months for sunitinib, corresponding to a 2.6-month (46%) improvement favoring cabozantinib. The PFS benefits of cabozantinib were independent of the patients’ IMDC risk groups (intermediate or poor risk) and the presence or absence of bone metastases at baseline.

The ORR was also significantly improved with cabozantinib compared with sunitinb (46% vs. 18%, respectively). With a median follow up of 22.8 months, median OS was 30.3 months for cabozantinib compared with 21.8 months for sunitinib (HR, 0.80).

A total of 150 patients were evaluable for safety. Ninety-nine percent of patients in both arms experienced at least one adverse event. The most common all-causality, grade 3 or grade 4 adverse events in the cabozantinib arm included hypertension (28%), diarrhea (10%), palmar–plantar erythrodysesthesia (8%), and fatigue (6%). In the sunitinib arm, the most common adverse events included hypertension (22%), fatigue (15%), diarrhea (11%), thrombocytopenia (11%), and oral mucositis (6%). Treatment-related grade 5 events occurred in three patients in the cabozantinib arm (acute kidney injury, sepsis, and jejunal perforation) and in two patients in the sunitinib arm (sepsis and vascular disorder).

Based on these results, Exelixis plans to submit a supplemental new drug application to the FDA for cabozantinib as a treatment for first-line advanced RCC.

Source: Exelixis, Inc.; October 10, 2016.

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