Adding Tecentriq to Cabometyx Doesn’t Improve Advanced RCC Outcomes

Author(s):

The addition of Tecentriq to Cabometyx did not improve the length of time patients lived without their disease getting worse for individuals with previously treated advanced kidney cancer, and came with additional side effects, too, recent research showed.

Adding Tecentriq (atezolizumab) to Cabometyx (cabozantinib) did not improve clinical outcomes for patients with metastatic renal cell carcinoma (kidney cancer), and further, the drug caused additional side effects for this patient population as well, according to findings from the phase 3 CONTACT-03 trial that was recently published in the journal, The Lancet.

“The aim of this study was to determine whether adding (Tecentriq) to (Cabometyx) delayed disease progression and prolonged survival in patients with disease progression on or after previous immune checkpoint inhibitor treatment,” the study authors wrote.

Checkpoint inhibitors (which are drugs that use patients’ immune systems to fight cancer) and targeted therapies have been making headway as the first line therapy for patients with advanced renal cell carcinoma, though sometimes patients’ disease will stop responding to or even progress (get worse) on these therapies. Once that happens, clinicians must determine what the best next line of therapy would be.

CONTACT-03 was a multicenter trial that was conducted in 135 cancer treatment centers in 15 countries. The study included 522 patients with locally advanced (disease that has spread to or beyond the surrounding areas of the kidney) or metastatic (disease that has spread elsewhere in the body) renal cell carcinoma that was previously treated with an immune checkpoint inhibitor, though eventually got worse on this treatment. Patients were randomly assigned to receive Tecentriq plus Cabometyx (263 patients) or Cabometyx alone (259 patients).

Patients were not eligible for the study if they:

Were treated with an anti-cancer therapy or radiotherapy within 14 days before the trials started
Previously received Cabometyx, or an mTOR inhibitor
Underwent treatment with more than one immunotherapy agent for locally advanced or metastatic kidney cancer
Were symptomatic of, had untreated or actively progressing metastases in the central nervous system
Had leptomeningeal disease or other conditions, such as hypercalcemia or pericardial effusion
Were pregnant or breast feeding

Percentage of patients who died or experienced disease progression at 15.2 months: 65% in the Tecentriq + Cabometyx group and 64% in the Cabometyx-only group

There was not a statistically significant difference in progression-free survival when Tecentriq was added to Cabometyx for advanced kidney cancer.

According to study findings, at an average follow-up of 15.2 months, 171 patients (65%) on the Tecentriq-containing regimen experienced disease progression or death, compared with 166 (64%) of patients on the Cabometyx-only regimen, showing that there was no significant difference between the two groups.

Further, the median progression-free survival — defined as the average time from treatment until death or disease worsening — was 10.6 months in the Tecentriq plus Cabometyx group, and 10.8 months in the Cabometyx-only group. Once again, the researchers did not find the difference in outcomes to be statistically significant.

Eighty-nine (34%) and 87 (34%) patients in the Tecentriq-containing and Cabometyx-only groups, respectively, died. The average overall survival — defined as the time from treatment until death of any cause — was 25.7 months in the Tecentriq plus Cabometyx group, and not evaluable in the Cabometyx group, because not enough patients had died for the researchers to calculate an average.

Regarding treatment regimen toxicity, serious side effects occurred in 126 (48%) of patients treated with Tecentriq plus Cabometyx, and 84 (33%) in the Cabometyx-only group, with side effect-related deaths occurring in 17 (6%) and nine (4%) patients in the two-drug and single-agent groups, respectively.

“The addition of (Tecentriq) to (Cabometyx) did not improve clinical outcomes and led to increased toxicity,” the researchers wrote. “These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials.”

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.