A targeted kinase inhibitor added to a two-drug immunotherapy combination slowed the progression of advanced kidney cancer in previously untreated patients, according to research led by Toni K. Choueiri, MD. Dr. Choueiri, who is the Director of the Lank Center for Genitourinary Cancer at Dana-Farber Cancer Institute, will present results of the ongoing COSMIC-313 pivotal phase III clinical trial on Sunday, September 12, during the European Society of Medical Oncology (ESMO) Congress 2022 (Abstract LBA8).
“Patients who received the kinase inhibitor cabozantinib in addition to checkpoint blockers nivolumab and ipilimumab experienced significantly improved progression-free survival compared to those who received only nivolumab and ipilimumab,” explained Dr. Choueiri.
Toni K. Choueiri, MD
Patients treated with the three-drug combination had a 27% lower risk of disease progression or death compared to those on the two immunotherapy drugs. That progression-free survival advantage met the primary endpoint. The median progression-free survival was not yet reached in the three-drug patient group, compared to a progression-free survival rate of 11.3 months in patients receiving nivolumab and ipilimumab.
“This is the first study to evaluate a triplet therapy against a contemporary immune-oncology doublet control, and it was designed to answer an important question of whether adding cabozantinib to dual checkpoint inhibition can improve outcomes for this patient population,” said Dr. Choueiri. “The initial findings provide a clear look at the efficacy and safety profile of this triplet therapy and demonstrate a significant progression-free survival benefit.”
KEY POINTS
- Patients treated with the three-drug combination had a 27% lower risk of disease progression or death compared to receiving just nivolumab and ipilimumab.
- COSMIC-313 trial is the first phase III trial in metastatic RCC to use nivolumab plus ipilimumab, a contemporary standard of care, as the control arm.
The patients have been followed for between 17.7 and 20 months. Overall survival is a secondary endpoint of the COSMIC-313 trial. At this stage of the trial, there was no significant survival benefit for the three-drug combination, so the trial will continue to the next analysis of overall survival.
The trial included 855 previously untreated patients with advanced or metastatic renal cell cancer (RCC) who were judged to be at intermediate or poor risk for survival according to the International Metastatic RCC Database Consortium (IMDC) risk model. Nivolumab plus cabozantinib and nivolumab plus ipilimumab are both standard-of-care first-line treatments of advanced kidney cancer. This is the first phase III trial in metastatic renal cell carcinoma to use nivolumab plus ipilimumab as the control arm.
Nivolumab and ipilimumab both work by blocking immune checkpoints. Cabozantinib inhibits several cancer-promoting pathways including MET, VEGFR, and TAM, and “may enhance response to checkpoint inhibitors,” said Dr. Choueiri, thus providing an additive or synergistic benefit when combined with nivolumab and ipilimumab.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
