CAPItello-281 Trial Shows Capivasertib Plus Abiraterone Maintains Quality of Life in PTEN-Deficient Prostate Cancer

The Phase III CAPItello-281 trial has provided crucial insights into the patient experience of combining capivasertib查看药品详情 with abiraterone查看药品详情 in PTEN-deficient metastatic hormone-sensitive prostate cancer (搜索)搜索该疾病, demonstrating that the targeted therapy maintains overall quality of life despite increased early adverse events. The findings, presented by Daniel J. George, MD, FASCO, of Duke Cancer Institute查看公司主页 at the 2026 ASCO Genitourinary Cancers Symposium, offer important guidance for clinicians considering this first-in-class targeted approach.

Study Design and Patient Population

CAPItello-281 enrolled 1,012 patients with PTEN (搜索)搜索该靶点-deficient de novo metastatic hormone-sensitive prostate cancer (搜索)搜索该疾病, defined as absence of specific cytoplasmic staining in ≥90% of viable malignant cells by immunohistochemistry. Patients were randomized 1:1 to receive either capivasertib查看药品详情 plus abiraterone查看药品详情/prednisone查看药品详情 or placebo plus abiraterone/prednisone, both administered with androgen deprivation therapy.

The study utilized an intermittent dosing schedule for capivasertib查看药品详情 at 400 mg twice daily (4 days on, 3 days off), specifically selected to maintain efficacy while mitigating cumulative side effects. Of the enrolled patients, 503 in each treatment arm received at least one dose of study therapy, with median treatment durations of 13.6 months in the capivasertib arm and 14.9 months in the placebo arm.

Quality of Life Outcomes Remain Stable

Patient-reported outcomes were assessed using the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire, with completion rates of 60.9% in the capivasertib查看药品详情 arm and 62.8% in the placebo arm. The analysis revealed no clinically meaningful differences between treatment arms in key quality of life measures.

For the FACT-P total score, the difference between treatment arms was only 0.4 points (95% CI −1.97 to 2.78), well below the predefined clinically meaningful threshold of ≥10 points. Similarly, physical wellbeing showed a difference of −0.4 points (95% CI −0.89 to 0.14), and functional wellbeing demonstrated a difference of −0.3 points (95% CI −1.01 to 0.37), both below the ≥3-point threshold for clinical significance.

However, time to deterioration in physical wellbeing occurred earlier in the capivasertib查看药品详情 arm, with a hazard ratio of 1.43 (95% CI 1.15−1.78). This difference was primarily driven by symptomatic adverse events such as diarrhea and rash occurring early in treatment. Importantly, no differences were observed between treatment arms in time to deterioration for FACT-P total score (HR 1.10; 95% CI 0.89−1.37) or functional wellbeing (HR 1.06; 95% CI 0.86−1.32).

Manageable Toxicity Profile

The adverse event profile was consistent with known AKT (搜索)搜索该靶点 inhibitor toxicities, with the most common events being diarrhea, rash, and hyperglycemia. These on-target effects occurred early during treatment and were generally manageable with supportive care and dose modifications.

Diarrhea occurred in 51.9% of patients receiving capivasertib查看药品详情 versus 8.0% with placebo, with a median time to onset of 12 days compared to 142 days in the placebo group. The toxicity led to dose reduction in 4.4% of patients, treatment interruption in 12.5%, and discontinuation in only 1.0%. Supportive therapy was required in 33.2% of patients, with 47.3% recovering or in recovery at the time of analysis.

Rash affected 35.4% of capivasertib查看药品详情 patients versus 7.0% receiving placebo, with a median onset of 13 days. This toxicity more frequently required treatment modifications, including dose interruption in 16.9%, dose reduction in 8.5%, and discontinuation in 4.8% of patients. Supportive therapy was administered in 29.0% of cases.

Hyperglycemia was observed in 38.0% of the capivasertib查看药品详情 arm compared with 12.9% in the placebo arm, with a median time to onset of 54 days versus 114 days. Treatment modifications included dose reduction in 6.6%, dose interruption in 10.9%, and discontinuation in 1.0%, with supportive therapy given to 25.2% of patients.

Clinical Implications

Despite the higher adverse event rates, approximately 80% of patients were able to continue treatment with the capivasertib查看药品详情 combination. The early occurrence of toxicities corresponded with the timing of treatment discontinuations, with 63% of capivasertib discontinuations occurring within the first 3 months. After this initial period, discontinuation rates became more parallel between arms, suggesting that early toxicity management is crucial for treatment continuation.

The findings build upon previously reported efficacy data showing that capivasertib查看药品详情 plus abiraterone查看药品详情 extended median radiographic progression-free survival to 33.2 months compared to 25.7 months with placebo, representing a 7.5-month improvement (HR 0.81; P = .034). Post hoc analyses suggested that patients with higher levels of PTEN (搜索)搜索该靶点 deficiency may derive greater benefit from the combination.

These results support the incorporation of AKT (搜索)搜索该靶点 pathway inhibition into treatment strategies for molecularly defined prostate cancer (搜索)搜索该疾病 populations, offering a targeted approach for patients with PTEN (搜索)搜索该靶点 loss while preserving functional wellbeing during therapy. The combination represents a potential first-in-class targeted treatment for patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (搜索)搜索该疾病, with manageable toxicities that do not significantly compromise overall quality of life.