BREAKPOINT: Cabozantinib Efficacious After Treatment with First-Line Immunotherapy

2021 Year in Review - Renal-Cell Carcinoma

Cabozantinib is a tyrosine kinase inhibitor (TKI) that is approved for use in combination with the immune checkpoint inhibitor nivolumab in the first-line setting and as monotherapy in all patients with advanced renal-cell carcinoma (RCC).1 However, there are limited data on the effectiveness of cabozantinib after first-line treatment with immune checkpoint inhibitors either alone or in combination with TKIs.2

In a prospective, open-label, phase 2 study, once-daily cabozantinib 60 mg was evaluated in 22 patients with advanced RCC who had previously received either adjuvant or first-line therapy with an anti–PD-1/PD-L1 checkpoint inhibitor. Previous immunotherapy could be either as a single agent or in combination with another TKI or anti–CTLA-4. Progression-free survival was the primary end point. Secondary end points included overall survival, objective response rate, and safety.2

The median age of participants was 59.5 years, and 69.5% were male. Patients had received a median of 4.3 months of previous therapy with anti–PD-1/PD-L1 inhibitors.2

On average, patients received cabozantinib for 4.7 months. The objective response rate was 27.2% (all partial responses). An additional 22.7% of patients achieved stable disease. After a median follow-up of 7.2 months, the median progression-free survival was 7.2 months.2

The most common adverse events (AEs) included hand–foot syndrome, diarrhea, hypothyroidism, mucositis, and fatigue. Grade 3 AEs were reported in 22.7% of patients. Grade 3 hand–foot syndrome was reported in 4.5% of patients. AEs led to treatment discontinuation in 2 patients. Cabozantinib dose interruption was reported in 63.6% of patients and was caused by AEs in 90% of cases. The most common reasons for cabozantinib dose interruption included hand–foot syndrome (13.9%), liver dysfunction (13.9%), diarrhea (11.6%), nausea and vomiting (11.6%), and fatigue (9.3%). AEs led to dose reduction in 22.7% of cases.2

According to the study investigators, this is the first prospective phase 2 study evaluating cabozantinib safety and efficacy after treatment with an immune checkpoint inhibitor. They concluded that cabozantinib is a tolerable agent with efficacy after immunotherapy.2


  1. Cabometyx (cabozantinib) tablets, for oral use [prescribing information]. Exelixis; September 2021.
  2. Procopio G, Pircher C, Claps M, et al. A phase II open-label study of cabozantinib after first-line treatment including an immune-checkpoint combination in patients with advanced or unresectable renal cell carcinoma: the BREAKPOINT trial (MeetUro trial 03 - EnduraCT number 2018-000582-36). J Clin Oncol. 2021;39(6_suppl):Abstract 326.

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