‘Potentially Practice-Changing’: Targeted Therapy Shown To Improve Survival For Men With Certain Subtype of Advanced Prostate Cancer

The CAPItello‑281 clinical trial enrolled men with de novo metastatic hormone-sensitive prostate cancer (mHSPC), which means their cancer already spread beyond the prostate at the time of diagnosis. These tumors still respond to hormone therapy, also known as androgen deprivation therapy (ADT), which is the backbone of first-line treatment.

However, in the trial researchers tested whether adding something called an AKT inhibitor, capivasertib, to the standard treatment of abiraterone plus prednisone with ADT could improve outcomes. Abiraterone (Zytiga) is usually given with low‑dose prednisone (a steroid) to help balance side effects. Abiraterone blocks CYP17, an enzyme the body uses to make androgens like testosterone, and prednisone helps reduce inflammation and ease some of the treatment‑related issues that can occur when androgen production is blocked.

The results showed an improvement in progression-free survival for men with a specific type of advanced prostate cancer known as PTEN-deficient.

Why PTEN Status Matters

PTEN is a tumor suppressor gene. When it’s lost, cancer cells gain a growth advantage by overactivating cell regulation pathways like PI3K and AKT. PTEN-deficient tumors tend to behave more aggressively and do not respond as well to current standards of care.

Essentially, when there is a PTEN deficiency, it helps “identify a pathway that is targetable” for cancer cells, Dr. Stephen Freedland, professor of urology at Cedars-Sinai in Los Angeles, California, explains. For patients, the more extensive the PTEN loss within the tumor, the worse the prognosis tends to be.

Understanding PTEN status early can help guide more precise treatment decisions — potentially steering eligible patients toward targeted combinations.

WATCH: Understanding the Types of Metastatic Prostate Cancer

Breaking Down The Data

In men with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC), adding capivasertib to abiraterone and prednisone on top of ADT produced a significant radiographic progression‑free survival benefit.

• Median rPFS: 33.2 months with capivasertib vs. 25.7 months with placebo
• Improvement: 7.5 months in median rPFS

An overall survival benefit was not yet determined as the trial is ongoing.

Investigators also observed that the benefit of capivasertib appeared to grow as the definition of PTEN loss became more stringent. While radiographic progression-free survival in the capivasertib arm remained relatively stable, outcomes in the placebo arm worsened as PTEN loss increased.

The most common side effects with capivasertib were:

• Diarrhea (51.9%)
• High blood sugar (38.0%)
• Rash (35.4%)

All are consistent with known effects of AKT inhibition.

WATCH: Treatment Sequencing: What To Expect For Castration-Resistant Prostate Cancer

Looking To The Future

Experts say the findings push prostate cancer care further toward biomarker-driven first-line treatment.

Dr. Tanya Dorff, a medical oncologist and the Head of the Genitourinary Cancers Program at City of Hope, California, notes that clinicians will increasingly need standardized PTEN immunohistochemistry testing alongside routine molecular sequencing to identify patients most likely to benefit.

If supported by regulatory decisions and additional evidence, CAPItello‑281 could shift first-line therapy for a clearly defined subgroup — men with PTEN-deficient metastatic hormone-sensitive prostate cancer — toward a targeted triplet regimen: androgen deprivation therapy (ADT) + abiraterone/prednisone + capivasertib.

Dr. Alexandra Drakaki of UCLA believes the data are poised to influence real‑world practice.

“When we now have patients with PTEN loss, and they’re newly diagnosed with metastatic castration‑sensitive prostate cancer, we should be able to combine our current standard of care with abiraterone and prednisone,” she notes.

Questions To Ask Your Doctor

• Have I been tested for PTEN deficiency?
• Should I consider/am I able to add capivasertib to my treatment plan?
• What side effects should I be aware of?

Learn more about SurvivorNet's rigorous medical review process.

---