FDA Approves Frontline Cabometyx for Advanced Kidney Cancer

Cabometyx (cabozantinib) was granted approval by the Food and Drug Administration (FDA) for previously untreated patients who have advanced renal cell carcinoma (RCC).

Cabometyx (cabozantinib) was granted approval by the Food and Drug Administration (FDA) for previously untreated patients who have advanced renal cell carcinoma (RCC). The approval is based on data from the CABOSUN trial, that showed improvements in progression-free survival (PFS) for patients on Cabometyx compared to those who were given Sutent (sunitinib).

In the phase 2 study, first-line treatment with Cabometyx reduced the risk of progression or death by 52 percent compared with Sutent for patients with advanced RCC. The median PFS was 8.6 months with Cabometyx versus 5.3 months for Sutent. The approval was granted approximately two months ahead of an FDA deadline.

“The CABOSUN trial enrolled treatment-naïve patients with advanced kidney cancer, including those who are known to fare poorly, such as patients with intermediate- or poor-prognostic factors and those with bone metastases or multiple sites of metastatic disease,” lead investigator Toni Choueiri, M.D., director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, said in a statement. “Physicians are already experienced in using Cabometyx in the second-line advanced RCC setting, and it is a much-needed advance to also now have Cabometyx as an option for their patients with previously untreated advanced RCC.”

The CABOSUN trial involved 157 poor- and intermediate-risk patients with advanced RCC, a subgroup of patients with worse prognosis and survival compared with patients who advanced RCC and favorable risk characteristics. Intermediate-risk patients accounted for 81 percent of the study population.

The objective response rate with Sutent was 20 percent compared with 9 percent for Sutent. When including those with stable disease, the over disease control rate was 75 percent with Sutent versus 47 percent for Sutent.

The updated survival analysis occurred after a median follow-up of 30.8 months and showed a median OS of 26.6 months in the Cabometyx arm versus 21.2 months in the Sutent arm. The difference represented a 20 percent reduction in the hazard ratio in favor of Cabometyx—a difference that did not achieve statistical significance.

The patient population had a median age of about 63. Key clinical features included bone metastases in about 36 percent of patients, prior nephrectomy in 75 percent and three or more metastatic sites in about 35 percent. The most common sites of metastasis were lung (70 percent), lymph nodes (55 percent), and bone (38 percent).

Cabometyx showed similar superiority to Sutent across all prespecified patient subgroups, including risk, bone metastases, and MET status. In those with poor-risk disease, there was a 69 percent reduction in disease progression or death. In the intermediate group, the HR for PFS was 0.52 in favor of Cabometyx.

Patients were randomized 1-1 to receive oral Cabometyx at 60 mg once daily (79 patients) or oral Sutent at 50 mg daily for four weeks on/two weeks off (78 patients). Treatment was administered until disease progression or intolerable toxicity.

An analysis of adverse events (AEs) showed that treatment with cabozantinib was associated with higher any-grade rates of diarrhea than sunitinib (73 percent vs 55 percent), hypertension (67 percent vs 44 percent), liver enzyme elevation (AST, 60 percent vs 31 percent; ALT, 55 percent vs 28 percent), decreased appetite (47 percent vs 32 percent) and weight loss (32 percent vs 17 percent, dysgeusia (41 percent vs 29 percent), and palmar-plantar erythrodysesthesia (42 percent vs 33 percent). Treatment with sunitinib versus cabozantinib led to higher rates thrombocytopenia (61 percent vs 38 percent), anemia (46 percent vs 33 percent), nausea (39 percent vs 32 percent), neutropenia (35 percent vs 15 percent) and leukopenia (35 percent vs 12 percent).

“We at the Alliance for Clinical Trials in Oncology are very gratified that the CABOSUN study supported the approval of Cabometyx for the potential first-line treatment of all patients with advanced renal cell carcinoma. This trial exemplifies how NCI-sponsored studies can be efficient, accrue rapidly, and yield results highly relevant to the field,” Michael J. Morris, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary (GU) Committee, said in a statement.