Novel Therapy Demonstrates Limited Activity and Poor Safety Outcomes in Patients With Metastatic Renal Cell Carcinoma

Treatment with sapanisertib did not result in significant activity or a favorable safety profile in patients with refractory metastatic renal cell carcinoma, according to study results presented at the 2021 ASCO Genitourinary Cancers Symposium.

“Sapanisertib had poor tolerability and minimal activity in patients with treatment refractory metastatic (renal cell carcinoma), and there was no clear benefit among patients with (mechanistic target of rapamycin [mTOR]) or (phosphatase and tension homolog [PTEN]) alterations,” lead study author Dr. Bradley McGregor, clinical director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, said in a virtual presentation of the data.

Thirty-eight patients (median age, 62 years) with clear cell metastatic renal cell carcinoma who had received two or more previous lines of treatment and with non-clear cell metastatic renal cell carcinoma who received one or more previous line of treatment were enrolled onto the multicenter, phase 2 study.

Patients underwent a mandatory baseline biopsy that evaluated PTEN status and more than 477 genes, including TSC1, TSC2, mTOR, PIK3CA, and PTEN, prior to receiving 30 milligrams of oral sapanisertib weekly.

Measuring objective response rate (the proportion of patients who had a complete or partial response to treatment) was the main goal of the study. Additional goals included assessing progression-free survival, overall survival, safety and toxicity of the drug.

Most of the patient population had clear cell disease (73.7%), and the rest had non-clear cell renal cell carcinoma (26.3%). Moreover, most patients had intermediate-risk disease (76.3%), followed by favorable- (13.2%) and poor-risk disease (10.5%).

Treatment options following progression on a checkpoint inhibitor and VEGF tyrosine kinase inhibitor are limited for patients with metastatic renal cell carcinoma. Approved rapalogs (a drug class), which have modest activity in the disease, inhibit only mTORC1 (a specific protein), whereas sapanisertib inhibits the entire mTOR pathway by targeting mTORC1 and mTORC2.

Most patients received four or more prior lines of therapy (39.5%). Though, patients who received one (13.2%), two (21.1%), and three (13.2%) prior lines of therapy were also represented. There were five patients who had an unknown number of prior treatments.

After a median follow-up of 10.4 months, treatment with the study drug induced an objective response rate of 5.3%. Median progression-free survival was 2.5 months and the median overall survival was 11.2 months.

The data showed that two patients experienced an unconfirmed partial response, 15 patients had stable disease, 17 patients experienced disease progression and two were not evaluable.

At the time of data stopped being collected, two patients remained on treatment. Of the remaining 36 who discontinued treatment, 29 occurred because of progressive disease and four reached an unacceptable toxicity.

No clear benefit between mTOR and PTEN alterations and clinical benefit with sapanisertib was reported.

Side effects related to treatment with sapanisertib included, but were not limited to, nausea (50%), fatigue (39%), diarrhea (18%), constipation (11%) and dehydration (8%). There were no grade 4 or 5 (more serious or severe) side effects associated with the treatment.

“Additional work is needed to find new targets for patients with advanced RCC,” concluded McGregor.

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