TKI Inhibitor Improves Survival in Metastatic Kidney Cancer

Disease progression or death was reduced by 34 percent for patients on Cabometyx (cabozantinib) compared to Sutent (sunitinib) when used as a first-line treatment for patients with metastatic renal cell carcinoma (RCC), according to results from the phase 2 CABOSUN trial published in the Journal of Clinical Oncology.

The median progression-free survival (PFS) was 2.6 months higher with Cabometyx versus Sutent. The overall response rate (ORR) was 46 percent versus 18 percent, respectively.

“In this smaller trial, cabozantinib was able to improve outcomes compared with sunitinib. The results showed that the primary endpoint, which was progression-free survival, was prolonged with cabozantinib over sunitinib,” lead investigator Toni K. Choueiri, M.D., clinical director, Lank Center for Genitourinary Oncology, director, Kidney Cancer Center, senior physician, Dana-Farber Cancer Institute, said in an interview with CURE.

“The results were not just statistically significant but also clinical relevant and corresponded to a decrease in the hazard of progression or death of over 30 percent,” Choueiri added. “This has the potential to change the standard of care and how we treat frontline advanced RCC.”

Between July 2013 and April 2015, the open-label, randomized phase 2 CABOSUN trial enrolled 157 patients with intermediate- or poor-risk locally advanced or metastatic clear-cell RCC. The Alliance for Clinical Trials in Oncology conducted the trial under a collaboration between Exelixis and the NCI’s Cancer Therapy Evaluation Program.

Patient characteristics were well balanced between the treatment arms. The median age across the entire patient population was 63 years (range, 31-87), 78 percent of patients were male, and 92 percent of patients were white. Thirty-six percent of patients had bone metastases and 75 percent of patients had prior nephrectomy. Patients had an ECOG performance status of 0 (45.9 percent), 1 (41.4 percent) or 2 (12.7 percent).

Patients were randomized in a 1-1 ratio to 60 mg once daily of Cabometyx (79 patients) or 50 mg once daily (four weeks on, two weeks off) of Sutent (78 patients). The primary outcome measure was PFS, with secondary endpoints including overall survival (OS) and ORR.

The median PFS was 8.2 months in the Cabometyx group compared with 5.6 months in the Sutent cohort.

The median OS was 30.3 months in the Cabometyx arm versus 21.8 months in the Sutent arm.

In 87 percent of the Cabometyx arm, there was some reduction in target lesions, compared with 44 percent of the Sutent cohort. The stable and progressive disease rates were 33 percent versus 36 percent and 18 percent versus 26 percent, respectively.

Adverse events (AEs) of any grade occurred in approximately 99 percent of each arm. The most common all-grade AEs with Cabometyx versus Sutent included fatigue (85.9 percent vs 81.9 percent), hypertension (80.8 percent vs 68.1 percent), diarrhea (71.8 percent vs 52.8 percent), increased AST (61.5 percent vs 31.9 percent) and increased ALT (55.1 percent vs 27.8 percent).

Grade 3 or higher AEs occurred in 66.7 percent of the Cabometyx arm versus 68.1 percent of the Sutent arm. Common grade 3 or higher AEs included diarrhea (10.3 percent with Cabometyx vs 11.1 percent with Sutent), fatigue (6 percent vs 15 percent), hypertension (28.2 percent vs 22.2 percent), palmar-plantar erythrodysesthesia (7.7 percent vs 4.2 percent) and fatigue (6.4 percent vs 15.3 percent).

Dose reductions occurred in 58 percent and 49 percent of the Cabometyx and Sutent arms, respectively. There were 16 AE-related discontinuations in each arm.

Cabometyx is approved in the United States and Europe as a treatment for patients with advanced RCC who have received prior antiangiogenic therapy.