Cabometyx Plus Opdivo, Yervoy Boosts Advanced Kidney Cancer Outcomes

Adding Cabometyx to Opdivo and Yervoy improved progression-free survival in patients with advanced kidney cancer, recent research showed.

Patients with previously untreated advanced renal cell carcinoma (kidney cancer) who have intermediate- or poor-risk diseasetended to have a longer progression-free survival (time from treatment until disease worsens) when treated with Cabometyx (cabozantinib) plus Opdivo (nivolumab) and Yervoy (ipilimumab), compared to those only treated with Opdivo and Yervoy, according to research data from the ongoing phase 3 COSMIC-313 trial that was published in the New England Journal of Medicine.

Cabometyx is an oral drug that works by inhibiting receptor tyrosine kinases like RET, MET, VEGFR2 and others, which are involved in cell-to-cell communication and could play a role in tumor cell growth. Meanwhile, Opdivo and Yervoy, which are given intravenously, block certain proteins that help cancer cells hide from the immune system (thereby allowing them to safely grow and reproduce). By inhibiting these proteins, the immune system — namely T cells — can recognize cancer tumor as foreign and dangerous invaders and attack the cancer.

Now, research is showing that combining these two types of treatment could be a promising option for patients with advanced kidney cancer. Additional trial data presented at the 2023 American Society of Clinical Oncology Meeting also showed that that three-drug regimen could be beneficial in patients with renal cell carcinoma with variant histologies (non clear-cell renal cell carcinoma) as well.

READ MORE: Three-Drug Regimen Is Promising Across Kidney Cancer Subtype

“Among patients with previously untreated, advanced renal-cell carcinoma who had intermediate or poor prognostic risk, treatment with (Cabometyx) plus (Opdivo) and (Yervoy) resulted in significantly longer progression-free survival than treatment with nivolumab and ipilimumab alone,” the researchers wrote.

The trial included 855 patients with advanced clear-cell renal cell carcinoma who had an intermediate or poor prognostic risk — which is determined by a variety of factors, such as the patient’s ability to perform daily tasks, time from diagnosis to systemic treatment and certain blood levels — and who have not previously been treated. A total of 428 patients were randomly assigned to receive Cabometyx (40 mg per day), Opdivo (3 mg per kilogram of body weight) and Yervoy (1 mg per kilogram), while the other 427 received only the two immunotherapy agents, Opdivo and Yervoy.

The main goal of the trial was to determine if adding Cabometyx to the regimen improved progression-free survival, which was assessed in the first 550 patients in the study. Additionally, the researchers analyzed overall survival (time from treatment until death of any cause), which was assessed in all patients in the study.

Study findings showed that in the 550 patients for whose progression-free survival data was collected (428 in the three-drug group, and 427 in the two-drug group), there was a 57% probability of progression-free survival at 12 months in the Cabometyx group, and 49% in the immunotherapy-only arm, meaning that after one year of treatment, there was a 57% and 49% chance, respectively, of the disease not progressing.

A total of 43% and 36% of patients in the three-drug and two-drug groups, respectively, responded to treatment. However, the researchers noted that there were more side effects in the Cabometyx group, “Grade 3 or 4 (side effects) were more common in the experimental group than in the control group.”

Seventy-nine percent of patients who received the Cabometyx-containing therapy experienced moderate to severe (grade 3 or 4) side effects, compared with 56% in the Opdivo plus Yervoy group.

While this portion of the COSMIC-313 trial is still ongoing, researchers are also enrolling patients on an expansion cohort analyzing 20 mg of Cabometyx, Opdivo and Yervoy.

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