The U.S. Food and Drug Administration approved capivasertib (Truqap) combined with abiraterone and prednisone in June 2026 for adults with PTEN-deficient metastatic hormone-sensitive prostate cancer, OncLive reported, making it the first targeted treatment authorized for this population as detected by an FDA-authorized test.
The approval rests on radiographic progression-free survival data from the phase 3 CAPItello-281 trial. At the primary data cutoff of Oct. 7, 2024, and a median follow-up of approximately 18 months, the median rPFS reached 33.2 months (95% CI, 25.8-44.2) for capivasertib compared with 25.7 months (95% CI, 22.0-29.9) for placebo (HR, 0.81; 95% CI, 0.66-0.98; P = .034). Overall survival was immature at 26% maturity (HR, 0.90; 95% CI, 0.71-1.15; P = .401).
CAPItello-281 showed delayed castration resistance in the primary analysis
Median time to castration resistance—a composite endpoint comprising radiographic progression, PSA progression, and symptomatic skeletal events—reached 29.5 months (95% CI, 22.1-36.8) in the capivasertib group versus 22.0 months (95% CI, 18.2-24.9) in the placebo group (HR, 0.77; 95% CI, 0.63-0.94; nominal P = .009). The HR for time to PSA progression was 0.73 (95% CI, 0.52-1.01; nominal P = .060), with 60 and 82 PSA progression events recorded in the respective arms.
Daniel George, who presented data from the study at the 2026 LUGPA Annual Meeting in Chicago, observed that numerous castration-resistance events in this population happened without an earlier PSA increase, highlighting the importance of imaging and symptom monitoring alongside PSA testing.
Longer follow-up sustained the benefit and delayed skeletal events
Updated results presented at the 2026 ESMO Congress in Madrid showed the rPFS benefit held: median rPFS was 35.5 months in the capivasertib arm versus 26.0 months in the control arm (HR, 0.83; 95% CI, 0.70-0.99; nominal P = .033), a 9.5-month difference, according to Urology Times. Median symptomatic skeletal event-free survival reached 43.8 months (95% CI, 39.1-53.1) for patients receiving capivasertib compared with 35.9 months (95% CI, 32.1-42.4) for those on placebo (HR, 0.83; 95% CI, 0.69-0.99; nominal P = .044).
Subsequent anticancer therapy rates were comparable across the two arms (38.7% vs 40.8%), though subsequent chemotherapy use was slightly lower among those treated with capivasertib (25.6% vs 30.5%). Point estimates for overall survival favored capivasertib across disease-volume subgroups: HR 0.74 (95% CI, 0.49-1.11) in high-volume disease with visceral metastases, 0.89 (95% CI, 0.70-1.14) in high-volume disease without visceral metastases, and 0.70 (95% CI, 0.42-1.15) in low-volume disease, Urology Times reported.
Post hoc exploratory analyses indicated that the OS hazard ratio shifted further in favor of benefit as the PTEN-loss threshold rose. Among patients with at least 95% PTEN loss, the HR was 0.76 (95% CI, 0.61-0.93), with median OS of 57.4 months versus 41.1 months. “Of course, this is post hoc analysis. We need to be very cautious,” Karim Fizazi cautioned.
The CAPItello-281 trial and FDA approval of capivasertib in PTEN-loss #mHSPC. @EHeath4100 @MayoClinic joins @zklaassen_md @GACancerCenter to discuss the FDA approval of capivasertib for PTEN-deficient metastatic hormone-sensitive prostate cancer, reviewing CAPItello-281 data in… pic.twitter.com/o3Q5A8KOsM
Side effects and quality-of-life measures shaped the safety picture
Among the 503 patients who received capivasertib, the most common adverse events were diarrhea (52.7%), hyperglycemia (40.4%), and rash (36.4%). Grade 3 or higher rates were 6.4%, 11.3%, and 12.7%, respectively. Diabetic ketoacidosis occurred in six patients (1.2%) in the capivasertib arm and one patient (0.2%) in the placebo arm, with no new cases since the primary analysis. Overall, grade 3 or higher adverse events occurred in 67.0% of the capivasertib arm versus 40.4% of the placebo arm, and adverse events led to discontinuation in 18.3% versus 4.8%.
| Adverse event | Capivasertib, any grade | Capivasertib, grade 3+ | Placebo, any grade |
|---|---|---|---|
| Diarrhea | 52.7% | 6.4% | 9.5% |
| Hyperglycemia | 40.4% | 11.3% | 13.9% |
| Rash | 36.4% | 12.7% | 8.0% |
Patient-reported outcomes told a more complicated story. According to the Functional Assessment of Cancer Therapy–Prostate questionnaire, the median time until a clinically meaningful deterioration in physical well-being was 7.2 months (95% CI, 4.5-10.0) for capivasertib versus 14.6 months (95% CI, 8.1-NC) for placebo (HR, 1.43; 95% CI, 1.15-1.78). Time to decline in functional well-being (HR, 1.06) and in total FACT-P score (HR, 1.10) was similar between arms. George described a grade-based approach to managing the toxicities, including holding capivasertib for grade 2 or higher diarrhea or rash until recovery, using antihistamines and oral corticosteroids for rash, and starting metformin for early hyperglycemia.
The final overall survival analysis is still ahead
The phase 3 findings were published in Annals of Oncology, which ScienceDirect hosts. The final OS analysis is planned after 522 deaths, corresponding to approximately 52% maturity. The FDA’s approval in June 2026 extends to adult patients with PTEN-deficient metastatic androgen pathway modulation–naive or –sensitive prostate cancer, a group formerly known as mHSPC.
Questions readers ask about capivasertib in PTEN-deficient prostate cancer
At the primary analysis, OS was immature at 26% maturity with an HR of 0.90 (P = .401). The final OS analysis is planned after 522 deaths, and updated subgroup point estimates numerically favor capivasertib across all disease-volume groups.
Adults with PTEN-deficient metastatic hormone-sensitive prostate cancer, confirmed by an FDA-authorized test, who are naive to or sensitive to androgen pathway modulation. PTEN-deficient tumors carry an adverse prognosis, and post hoc data suggest the benefit grows with the degree of PTEN loss.
Diarrhea, hyperglycemia, and rash, with grade 3 or higher events in 6.4%, 11.3%, and 12.7% of patients respectively, plus diabetic ketoacidosis in 1.2% of the capivasertib arm. Investigators manage these with dose holds, antihistamines, corticosteroids, and metformin.
🚨 FDA Approves Capivasertib in mHSPC CAPItello-281 establishes PTEN as a clinically actionable biomarker in metastatic hormone-sensitive prostate cancer. 🔹 First targeted therapy approved for PTEN-deficient mHSPC 🔹 rPFS: 33.2 vs 25.7 months (HR 0.81; p=0.034) 🔹 Benefit… pic.twitter.com/QeXgfEAZ41
Fizazi concluded at the ESMO Congress: “We believe that these results support capivasertib, ADT, and abiraterone as a first-in-class treatment for the PTEN-deficient mCSPC population with an adverse prognosis, and this applies to both populations, high-volume and low-volume [disease].”