# IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer

Source: https://onco.cc/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/  
OnCo record `paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding an AKT-blocking tablet to abiraterone delayed progression in the half of men who had lost PTEN, but at a considerable cost in side effects.

## Summary

A randomised, double-blind phase 3 trial at 200 sites in 26 countries in men with previously untreated asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer with progressive disease. Of 1,611 men screened, 1,101 were enrolled and randomised to ipatasertib 400 mg daily with abiraterone and prednisolone or to placebo with abiraterone and prednisolone, stratified by prior taxane, type of progression, visceral metastasis and tumour PTEN-loss status by immunohistochemistry. In the 521 men, 47%, whose tumours showed PTEN loss by immunohistochemistry, median radiographic progression-free survival was 16.5 months with placebo and 18.5 months with ipatasertib, hazard ratio 0.77, significant at the prespecified alpha. In the intention-to-treat population the difference was 16.6 against 19.2 months, hazard ratio 0.84, not significant at its alpha. Grade 3 or higher adverse events occurred in 39% of the placebo group and 70% of the ipatasertib group, with discontinuation for adverse events in 5% against 21%.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Lancet
- Year: 2021
- DOI: 10.1016/S0140-6736(21)00580-8
- Authors: Sweeney C, Bracarda S, Sternberg CN, et al.
- Findings: PTEN loss by immunohistochemistry in 521 of 1,101 men, 47%.; Radiographic progression-free survival 18.5 against 16.5 months in the PTEN-loss population, hazard ratio 0.77.; No significant difference in the intention-to-treat population at its prespecified alpha.; Grade 3 or higher adverse events in 70% against 39%, with discontinuation in 21% against 5%.
- What it means: It is the prospective test of the PI3K and androgen receptor feedback hypothesis in men, and it shows both halves of the answer: the biomarker-selected population benefits, and the benefit is small enough that the toxicity has to be weighed honestly.
- Caveats: A two-month median difference in radiographic progression-free survival, with overall survival not demonstrated here.; PTEN loss was defined by one immunohistochemistry assay; a different assay would define a different population.; One man in five stopped ipatasertib because of side effects.

## Sources

- Sweeney et al., Lancet 2021: IPATential150, ipatasertib with abiraterone in 1,101 men with metastatic castration-resistant prostate cancer split by PTEN loss: https://doi.org/10.1016/S0140-6736(21)00580-8
- PubMed: https://pubmed.ncbi.nlm.nih.gov/34246347/

## Connected records

- cancers: [Metastatic castration-resistant prostate cancer](https://onco.cc/cancers/prostate-mcrpc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [AKT](https://onco.cc/targets/akt/), [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [PTEN](https://onco.cc/targets/pten/)
- drugs: [Abiraterone acetate](https://onco.cc/drugs/abiraterone/), [Ipatasertib](https://onco.cc/drugs/ipatasertib/)
- pathways: [Androgen receptor signalling](https://onco.cc/pathways/ar-signaling/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/)
- terms: [Castration-resistant prostate cancer (CRPC)](https://onco.cc/terms/castration-resistance/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)
- biomarkers: [PTEN alteration (sequencing) and PTEN loss (IHC)](https://onco.cc/biomarkers/pten-alteration/)

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