Capivasertib (Truqap) + abiraterone + prednisone in PTEN-deficient metastatic hormone-sensitive prostate cancer (mAPMN/S). AstraZeneca. FDA-approved June 12, 2026, with the VENTANA PTEN (SP218) RxDx companion diagnostic.
Discover KOL Sentiment on CAPITELLO-281 →Design - Phase 3 capivasertib + abiraterone vs placebo + abiraterone (with ADT), PTEN-deficient de novo mHSPC (NCT04493853); VENTANA PTEN (SP218) companion diagnostic.
rPFS (primary) - Median 33.2 vs 25.7 mo, HR 0.81 (95% CI 0.66-0.98; P=0.034) - a 7.5-month improvement.
Secondary endpoints - Consistent benefit: time to castration resistance (HR 0.77), time to first subsequent chemotherapy (HR 0.79), symptomatic skeletal-event-free survival (HR 0.82).
OS - Immature at primary analysis (26.4% maturity); interim HR 0.90 - numerically favorable, no evidence of detriment.
Safety - Grade >=3 AEs 67% vs 40.4%; diarrhea, hyperglycemia, rash; severe hyperglycemia (including DKA) is a labeled warning.
Regulatory / drug - FDA approved June 12, 2026 (ODAC 7-1-1); AstraZeneca; capivasertib (Truqap) + abiraterone.
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.
Precision oncology in mHSPC just got real, but we need to drop the "binary biomarker" illusion. With CAPItello-281 and TALAPRO-3, the "mutation: yes/no" logic falls short. We are navigating gradients, not switches. A thread on clinical triage. 1/6
2/6 Take CAPItello-281: PTEN loss isn't an on/off switch. At 100% PTEN loss, the control arm (abiraterone + ADT) crashes to a 22.1-month median rPFS. The tumor bypasses the AR pathway; Capivasertib rescues this effectively, maintaining a 34.1-month rPFS (HR 0.68).
3/6 NGS alone often misses this nuance, providing a mostly binary readout. A standard IHC stain, however, gives us the percentage of PTEN protein loss. Mandating this rapid, inexpensive stain alongside routine genomic testing in de novo mHSPC might give us the depth to triage.
4/6 TALAPRO-3 highlights a similar need for nuance. Talazoparib delivers a massive rPFS benefit for BRCA1/2 mutations (HR 0.37). Non-BRCA HRR mutations still benefit, but the efficacy softens to a 0.57 HR. We have to weigh this carefully against the toxicity profile.
5/6 That non-BRCA HR 0.57 demands clinical tact. 51% of patients on talazoparib hit grade 3+ anemia. For a frail patient with a CHEK2 mutation, does the efficacy outweigh the hematological toll? We are moving away from simple guideline flowcharts.
6/6 Throw PSMAddition into the frontline mix and mHSPC becomes a multidimensional puzzle. How do we sequence a patient with ATM mutation, 90%PTEN loss, and intense PSMA expression? Balancing these overlapping phenotypes w/o compromising mCRPC options is our next great challenge
ASTRAZENECA: TRUQAP COMBINATION APPROVED IN US AS FIRST AND ONLY TARGETED TREATMENT FOR PTEN-DEFICIENT METASTATIC HORMONE-SENSITIVE PROSTATE CANCER
Just in (again, Friday FDA notices): The @US_FDA approved Capivasertib (oral AKT inhibitor) for metastatic Hormone-Sensitive prostate Cancer with PTEN deficiency (by IHC; 90%+). 4/30: ODAC voted 7-1 for a favorable benefit-risk profile based on the CAPItello-281 Phase III https://t.co/zI7ImtGtFr https://t.co/2jcC5AdYFc
PTEN as a prognostic marker and clinical decision tool in #mHSPC: Multidisciplinary discussion. @Daniel_J_George, Neal Shore, MD, FACS, David Morris, MD, FACS & @neerajaiims review the CAPItello-281 Phase III trial, highlighting PTEN loss as a critical prognostic marker https://t.co/MdvJKdlOXy
Breaking new👉 today @US_FDA approved capivasertib (oral AKT inhibitor) for the metastatic HSPC/APMS #prostatecancer with PTEN deficiency👉personalized medicine continues to leap forward👉Capitello-281 ph3 trial summary👇 @OncoAlert @urotoday @AUC3_Official https://t.co/z7RAqgcq4Y https://t.co/kVh3RqmRIc
🚨 FDA Approves capivasertib Plus Abiraterone as First Targeted Therapy for PTEN-Deficient Metastatic Hormone-Sensitive Prostate Cancer Source AstraZeneca https://t.co/lNI5xBcu9K The FDA has approved capivasertib in combination with abiraterone and prednisone as the first https://t.co/E9k23Iz2AW
🚨 #GU26 – Day Highlights Prostate Cancer Today was not about incremental updates. It was about structural shifts in how we think. @OncoAlert @ASCO 1️⃣ Biology is finally driving decisions • PTEN-deficient mHSPC → AKT pathway targeting (CAPItello-281) • PARPi sequencing in https://t.co/xZm0SinVEc
GU @ASCO highlights from #GU26 with @PGrivasMDPhD ✅ CREST/POTOMAC (update) ✅ EV304/KeynoteB15 (new SoC) ✅ LITESPARK-011 & 022 ✅ CAPItello-281 Full 🗣️: ⭐️ On OncBrothers & @OncUpdates website ⭐️ “Oncology Brothers” podcast #OncTwitter #MedTwitter #gusm @OncoAlert https://t.co/ToC5o67KZI
FDA approved capivasertib + abiraterone/prednisone for PTEN-deficient metastatic prostate cancer. Grateful to have been one of the investigators in CAPItello-281. @US_FDA @APCCC_Lugano @OncoAlert @ONCOassist @OpenMedicineHQ @AnkaraUni https://t.co/fJsf0XB5oe https://t.co/HxF0wgiwQ0
FDA Approves Capivasertib Plus Abiraterone and Prednisone for Metastatic Prostate Cancer - The ASCO Post https://t.co/kkR0kL9Pkl
The @US_FDA approved the targeted therapy capivasertib with the hormone therapy abiraterone and the steroid prednisone for adults with PTEN-deficient metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer: https://t.co/LXMXYqS13L
In PTEN-deficient mHSPC, loss of PTEN drives PI3K/AKT pathway activation — an independent proliferative signal that androgen receptor pathway inhibitors alone cannot suppress, leading to worse outcomes. CAPItello-281 (NCT04493853) is a global Phase 3, double-blind trial that randomized 1,012 patients with de novo PTEN-deficient mHSPC 1:1 to capivasertib or placebo, each with abiraterone, prednisone/prednisolone and ADT, to test dual PI3K/AKT + AR blockade.
Median rPFS 33.2 vs 25.7 months — a 7.5-month improvement and 19% reduction in risk of radiographic progression or death (HR 0.81; 95% CI 0.66–0.98; P=0.034).
Consistent benefit across clinically relevant secondaries: time to castration resistance (HR 0.77), time to first subsequent chemotherapy (HR 0.79), and symptomatic skeletal event-free survival (HR 0.82).
OS was immature at the primary analysis (26.4% maturity); the interim HR was 0.90 (95% CI 0.71–1.15; P=0.401), numerically favoring capivasertib with no evidence of detriment. Longer follow-up is ongoing.
Grade ≥3 AEs occurred in 67% vs 40.4%. The most common any-grade AEs were diarrhea (51.9%), hyperglycemia (38.0%) and rash (35.4%) — early, on-target AKT-inhibition effects, generally manageable; ~80% of patients continued treatment. Severe hyperglycemia (including DKA and fatal outcomes) is a labeled warning.
CAPItello-281 is a Phase 3 randomized trial (NCT04493853) of the AKT inhibitor capivasertib (Truqap) plus abiraterone versus placebo plus abiraterone, each with androgen deprivation therapy, in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer. Radiographic progression-free survival was the primary endpoint.
Adding capivasertib to abiraterone improved radiographic progression-free survival: median rPFS was 33.2 versus 25.7 months (HR 0.81; 95% CI 0.66-0.98; P=0.034), a 7.5-month improvement and a 19% reduction in the risk of radiographic progression or death. Benefit was consistent across secondary endpoints such as time to castration resistance and symptomatic skeletal-event-free survival. Overall survival was immature (interim HR 0.90) with no evidence of detriment.
Yes. On June 12, 2026 the FDA approved capivasertib (Truqap) in combination with abiraterone for PTEN-deficient de novo metastatic hormone-sensitive prostate cancer, with the VENTANA PTEN (SP218) RxDx assay as the companion diagnostic to identify PTEN-deficient tumors. The approval followed an ODAC vote of 7-1-1.
Grade 3 or higher adverse events occurred in 67% of the capivasertib arm versus 40.4% with placebo. The most common any-grade toxicities were diarrhea (51.9%), hyperglycemia (38.0%), and rash (35.4%) - on-target AKT-inhibition effects that are generally manageable, with about 80% of patients continuing treatment. Severe hyperglycemia, including diabetic ketoacidosis and fatal outcomes, is a labeled warning requiring glucose monitoring.
CAPItello-281 applies to patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer. PTEN status is determined by the VENTANA PTEN (SP218) companion diagnostic, so the regimen is a biomarker-selected, targeted approach rather than a treatment for all mHSPC patients.
