Afinitor May Not Boost Outcomes in Non-Clear Cell Kidney Cancer

Post-surgical Afinitor (everolimus) did not improve the time patients lived without experiencing relapse — a statistic known as relapse-free survival (RFS) — or survival in patients with non-clear cell renal cell carcinoma (RCC), a subtype of kidney cancer, according to research published in JAMA Network Open.

The researchers analyzed data from the phase 3 EVEREST clinical trial testing Afinitor in adults with intermediate- or high-risk RCC who underwent a nephrectomy (surgical removal of the kidney). Half the patients in the trial were randomly assigned to receive adjuvant (post-surgical) Afinitor, while the other half received a placebo (inactive drug).

For this study, researchers specifically looked at data for patients with non-clear cell subtypes of kidney cancer: papillary RCC (109 patients) and chromophobe RCC (99 patients). Non-clear cell RCCs make up about 20 to 25% of kidney cancer diagnoses and their prognosis tends to be poor, according to the National Institutes of Health.

“While current practice guidelines recommend consideration of adjuvant [Keytruda (pembrolizumab)] or [Sutent (sunitinib)] for the treatment of patients with clear-cell RCC after nephrectomy, no such recommendations exist for patients with non-clear cell RCC,” the study authors wrote.

Relapse-Free Survival With Afinitor

In the papillary RCC group, 57 patients received Afinitor, while 52 received a placebo. After a median follow-up of 76 months (6.3 years), there was no statistically significant difference in RFS between the two groups, meaning that the researchers could not be sure that one group truly outperformed the other. Specifically, the five-year RFS was 62% and 70% in the Afinitor and placebo groups, respectively.

Meanwhile, in the chromophobe RCC group, 53 patients were treated with Afinitor and 46 were given a placebo. Again, there was no statistically significant difference in five-year RFS at 79% and 77% in the Afinitor and placebo groups, respectively.

READ MORE: Welireg Outperforms Afinitor in Advanced Clear Cell Kidney Cancer

At the time of data collection, median overall survival was not yet reached, indicating that not enough patients had died yet for researchers to calculate an average time from treatment until death.

However, the researchers did note that while the difference in data between the Afinitor and placebo groups were just shy of statistical significance, “a potential treatment benefit [with Afinitor] in these subgroups cannot be ruled out.”

Side Effects After Afinitor

Most patients in the subgroup analysis, regardless if they were treated with Afinitor or placebo, reported at least one side effect. The side effect rate was higher in the Afinitor group (96%) compared to the placebo group (81%).

Among all patients with non-clear RCC, 48% experienced a side effect that was severe or worse (grade 3), compared to 9% in the placebo group.

The most common side effects related to Afinitor were mucositis (inflamed mucous membranes), high triglyceride levels, fatigue and high glycemic levels.

There were no treatment-related deaths, but 54% and 51% of patients in the papillary and chromophobe RCC groups, respectively, stopped treatment before completing the full 54 weeks due to side effects, refusal, recurrence or unrelated reasons.

“While the use of adjuvant therapies has received US Food and Drug Administration approval for patients with clear-cell RCC, the non–clear cell cohorts remain an area of unmet need,” the researchers concluded.

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