Telaglenastat-Cabometyx Combination May Not Improve Survival in Pretreated Kidney Cancer Compared With Cabometyx Alone

In patients with metastatic clear-cell renal cell carcinoma, a type of kidney cancer, adding telaglenastat did not improve the efficacy of Cabometyx (cabozantinib) in improving progression-free survival, according to recent study results.

Telaglenastat is a glutaminase inhibitor that deprives tumor cells of glutamate, which inhibits growth and survival, according to the researchers.

“While the addition of telaglenastat to (Cabometyx) did not improve outcomes in this unselected RCC patient population, future studies of telaglenastat may be warranted to determine the effect of glutaminase inhibition in biomarker-driven patient populations with high dependence on glutamine/glutaminase and/or in combination with other therapeutic partners,” the researchers wrote in the study published in JAMA Oncology.

Limited Treatment Options

Treatment options are limited for pretreated patients with renal cell carcinoma, “underscoring the need for additional therapeutic options for heavily pretreated patients,” the study authors wrote.

In this study, researchers sought to evaluate if adding telaglenastat to Cabometyx would improve progression-free survival (time during and after treatment when the patient lives without disease progression). In particular, researchers analyzed data from 444 patients with metastatic clear-cell renal cell carcinoma, of whom were assigned either Cabometyx with telaglenastat (221 patients) or Cabometyx with placebo (174 patients). Of note, 62% of patients in the study were previously treated with immune checkpoint inhibitors.

Telaglenastat with Cabometyx did not significantly improve progression-free survival compared with placebo plus Cabometyx (median, 9.2 months versus 9.3 months, respectively).

Furthermore, overall response rates (percentage of patients with a partial or complete response to treatment) were 31% with the addition of telaglenastat and 28% with the addition of placebo. Two patients in each group had complete responses (the disappearance of cancer as a response to treatment), and partial responses (decrease in tumor size or the amount of cancer in the body as a response to treatment) were reported in 30% of patients in the telaglenastat group and 27% of those in the placebo group, respectively.

Duration of response (the time the disease responds to a treatment without growth or spread) was 12 months with telaglenastat and 11.2 months with placebo.

A preliminary evaluation of overall survival (time since the start of treatment when a patient with cancer is still alive) showed no difference between telaglenastat (22.2 months) and placebo (24.8 months).

Potential Explanations of Study Findings

The study authors explained that the lack of efficacy demonstrated with telaglenastat could be due to a low dosage. However, the dosage which was used in this study (800 milligrams twice per day) was established based on previous studies which demonstrated positive results.

Another possible reason, they added, could be that Cabometyx may not be the optimal therapeutic agent to combine with telaglenastat with the goal of inhibiting glutaminase. It is also possible that glutaminase is not an ideal target in this patient population, the study authors explained.

Side effects were similar in both groups, with severe or worse side effects occurring in 71% of patients in the telaglenastat group and 79% of patients in the placebo group. The most common side effects of this severity were high blood pressure (17% versus 18%) and diarrhea (15% versus 13%).

Of note, more patients discontinued cabozantinib when combined with placebo compared with telaglenastat (15% versus 10%), “suggesting that telaglenastat did not exacerbate (side effects) associated with (Cabometyx),” the study authors noted.

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