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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Tuesday, February 28, 2023
Sarah Elizabeth Fenton, MD, PhD, of Northwestern University, Chicago, and colleagues presented findings from the small phase I ADDITION trial at the 2023 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium (Abstract 174). The trial looked at alterations activating the PI3K-Akt pathway, which are found in almost half of patients with aggressive prostate cancer and frequently lead to an abrogated response to therapy with androgen receptor (AR) pathway inhibitors and poor outcomes. The combination regimen was found to be safe, with a partial response seen in some men who had PI3K alterations.
The single-arm study focused on the AR inhibitor darolutamid, the AKT inhibitor ipatasertib, and androgen-deprivation therapy (ADT). It included six patients with castration-resistant prostate cancer who had received a median of three prior systemic therapies in addition to ADT. Patients started with a lead-in of ipatasertib for 7 days at a starting dose of 400 mg/day, with plans to de-escalate in the case of at least two dose-limiting toxicities, which were identified in the first six patients. This was followed by ipatasertib combined with 600 mg of darolutamide. Although a phase II biomarker-selected cohort was planned, that portion of the study was later terminated prior to patient enrollment.
All patients completed the dose-limiting toxicities period, and no dose-limiting toxicities were observed. The recommended phase II dose of ipatasertib was determined to be 400 mg/day when given with darolutamide.
Two patients reported serious adverse events of grade 3 diarrhea related to ipatasertib. Two patients also reported serious adverse events not related to the study drugs: pyelonephritis (one patient, grade 3) secondary to obstruction and respiratory failure (one patient, grade 5) attributed to disease progression.
The median prostate-specific antigen progression-free survival was 3.35 months, and median radiographic progression-free survival was 2.91 months. A partial response to the combination therapy was seen in men with castration-resistant prostate cancer and known PI3K alterations.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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