GU Symposium 2021: Novel mTOR1/2 Inhibitor Under Study in Metastatic Kidney Cancer
Posted: Thursday, March 4, 2021
The mTORC1/2 inhibitor sapanisertib demonstrated minimal activity in patients with refractory metastatic renal cell carcinoma and offered no apparent benefit among patients with alterations in the mTOR/PTEN pathway. These phase II trial findings were presented by Bradley Alexander McGregor, MD, of the Dana-Farber Cancer Institute, Boston, on behalf of his colleagues at the virtual 2021 Genitourinary (GU) Cancers Symposium (Abstract 306).
This single-arm study enrolled 38 patients with metastatic renal cell carcinoma who had experienced disease progression on previous therapies. All patients had an Eastern Cooperative Oncology Group performance status of 0 to 2, and most patients (76%) had intermediate-risk disease by the International Metastatic RCC Database Consortium criteria. After undergoing a baseline biopsy, patients were treated with 30 mg of oral sapanisertib every week until disease progression or unacceptable toxicity. In addition to assessing the overall response rate, researchers also analyzed tissue biomarkers of mTOR pathway activation.
The median duration of therapy was 1.6 months (range, 0.3–13.8 months) after a median follow-up of 10.4 months. The overall response rate was 5.3%, with just 2 of the 38 patients responding to therapy. However, 31.6% of the enrolled patients had some tumor shrinkage throughout treatment. The median progression-free survival was 2.5 months.
Tumor sequencing revealed mTOR alterations in six patients: two with mutations in mTOR, three with mutations in PTEN, and one with a mutation in TSC1. An additional seven patients had reduced PTEN expression on immunohistochemistry. Patients with mutations in the mTOR pathway or with loss of PTEN expression had no difference in response to sapanisertib.
Grade 3 or higher treatment-related adverse events were noted in 12 patients (32%), and no patients had grade 4 or 5 toxicity. Six patients (16%) underwent dose reduction, and four (11%) discontinued treatment due to adverse events.
Disclosure: For a full list of authors’ disclosures, visit coi.asco.org.