Three-drug combo slows the progression of advanced kidney cancer

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In a study from Dana-Farber Cancer Institute, scientists found a three-drug combination could slow the progression of advanced kidney cancer in previously untreated patients.

Patients who received the kinase inhibitor cabozantinib in addition to checkpoint-blockers nivolumab and ipilimumab experienced strongly improved progression-free survival compared to those who received only nivolumab and ipilimumab

The team found patients treated with the three-drug combination had a 27% lower risk of progression or death compared to those on the two immunotherapy drugs.

That progression-free survival (PFS) advantage met the primary endpoint. The median PFS was not yet reached in the three-drug patient group.

The median PFS was 11.3 months for 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.

The team says 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.

In the study, the patients were 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.

Nivolumab plus cabozantinib and nivolumab plus ipilimumab are both standard of care first-line treatments for advanced kidney cancer.

This is the first phase 3 trial in metastatic renal cell carcinoma to use nivolumab plus ipilimumab as the control arm.

Nivolumab and ipilimumab both work by blocking immune checkpoints, molecular “brakes” that prevent the immune system from attacking cancer.

Releasing the brakes allows the immune T cell army to invade the tumors and kill the cancer cells.

Cabozantinib inhibits several cancer-promoting pathways including MET, VEGFR, and TAM, and may enhance response to checkpoint inhibitors, thus providing an additive or synergistic benefit when combined with nivolumab and ipilimumab.

If you care about kidney health, please read studies about a new way to detect the risk of chronic kidney disease, and cruciferous vegetables may help reverse kidney damage in diabetes.

If you care about cancer, please read studies that a low-carb diet could increase overall cancer risk, and vitamin D supplements strongly reduce cancer death.

The study was conducted by Toni Choueiri et al and presented at the European Society of Medical Oncology (ESMO) Congress 2022.

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