Clinical Edge

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mCRPC: First-line abiraterone + ipatasertib shows promise

Key clinical point: First-line abiraterone + ipatasertib demonstrated superior radiographic progression-free survival (rPFS) and antitumor activity than abiraterone + placebo in patients with PTEN-loss metastatic castration-resistant prostate cancer (mCRPC).

Major finding: The Median rPFS in PTEN loss by immunohistochemistry population was 18.5 months with ipatasertib vs 16.5 months with placebo (hazard ratio [HR], 0.77; P = .0335), and that in the intention-to-treat population was 19.2 months with ipatasertib vs 16.6 months with placebo (HR, 0.84; P = .0431). Serious adverse events were 40% with ipatasertib vs 23% with placebo.

Study details: In the phase 3 study IPATential150 trial, 1101 asymptomatic or mildly symptomatic patients previously untreated for mCRPC were randomly assigned to either ipatasertib + abiraterone + prednisone (n = 547) or placebo + abiraterone + prednisone (n = 554).

Disclosures: The study was funded by Hoffmann-La Roche, Ltd. The presenting author JS de Bono reported relationships with various pharmaceutical companies, including Roche.

Commentary

“Some success has been made in the development of treatments for metastatic castrate-resistant prostate cancer (mCRPC). However, it is still considered an incurable disease, and additional treatment options are needed. Approximately 40-50% of mCRPC tumors have loss of expression of the tumor suppressor PTEN. It has been postulated that inhibition of the PI3K/AKT pathway may be effective against tumors with PTEN loss. Ipatasertib is a potent pan-AKT inhibitor. In the phase III IPATential150 trial, patients with mCRPC were randomized to abiraterone/prednisone +/- ipatasertib. Coprimary endpoints included progression-free survival (PFS) in patients with tumors having PTEN loss and in the overall intent-to-treat (ITT) cohort. The PFS endpoint was met in the PTEN loss cohort but not in the ITT cohort. The modest activity in the PTEN loss cohort suggests that targeting the PI3K/AKT pathway could be part a future precision oncology-based approach to treatment of mCRPC.”

Mark Klein, MD

Citation:

de Bono JS et al. ESMO Virtual Congress 2020. 2020 Sep 20. Abstract LBA4.