Daniel George, MD, on PROs and tolerability data from CAPItello-281

In the following video, Daniel J. George, MD, highlights key patient-reported outcomes and tolerability findings from the phase 3 CAPItello-281 trial (NCT04493853), evaluating the addition of capivasertib (Truqap) to abiraterone (Zytiga) in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC). These findings were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California.¹

George is a medical oncologist at Duke Cancer Center in Durham, North Carolina.

According to George, data from the PRO analysis focused on results from the FACT-P assessment, which evaluates physical, functional, emotional, social, and prostate cancer–specific well-being. Compliance with PRO reporting was high, with 80.1% of patients in the capi+abi arm and 81.6% of patients in the placebo+abi arm completing assessments over time.

Notably, while physical well-being scores showed a higher rate of early deterioration in the capivasertib arm—defined as a 3-point or higher decline from baseline—this effect was largely confined to the first 6 to 12 weeks of therapy. By approximately 3 months, physical well-being scores rebounded, and trends between the treatment and control arms converged, suggesting a transient impact likely driven by early-onset adverse effects. There was a shorter time to deterioration in physical well-being with capivasertib (HR, 1.43; 95% CI, 1.15 to 1.78).

Importantly, this early decline in physical well-being did not appear to affect broader measures of daily functioning or overall health-related quality of life (HRQoL). Functional well-being scores were similar between treatment groups, with no meaningful differences in time to deterioration (HR, 1.06; 95% CI, 0.86 to 1.32). Likewise, time to deterioration in overall FACT-P total scores remained comparable between arms (HR, 1.10; 95% CI, 0.89 to 1.37).

George also noted that the safety profile of capivasertib in CAPItello-281 was consistent with known on-target effects of AKT inhibition, including rash, diarrhea, and hyperglycemia. These adverse events typically emerged early in the treatment course, with rash and diarrhea occurring within the first 2 weeks (median onset ~12–13 days) and hyperglycemia presenting later, at approximately 2 months. Higher rates of grade 3 or greater adverse events were observed in the capivasertib arm compared with placebo (67% vs 40.4%). However, most adverse events were manageable with standard supportive care interventions, including topical or systemic corticosteroids and antihistamines for rash, antidiarrheal agents such as loperamide (Imodium), and metformin for hyperglycemia. Dose interruptions were most frequently required for rash (16.9%), though permanent discontinuation due to these toxicities remained relatively low.

According to the authors, these data suggest that although capivasertib is associated with an increased burden of early, symptomatic adverse events, these effects do not appear to compromise longer-term functional status or overall HRQoL. In the context of previously reported efficacy benefits, including a significant improvement in radiographic progression-free survival in patients with PTEN-deficient disease, the PRO findings support the clinical feasibility of incorporating capivasertib into treatment strategies, provided that clinicians proactively manage early toxicities.

REFERENCE

1. George DJ, Clarke NW, De Santis M, et al. Patient reported outcomes (PRO) and tolerability of capivasertib (capi) plus abiraterone (abi) versus placebo (pbo) plus abi in patients (pts) with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC): CAPItello-281. J Clin Oncol. 2026;44. (suppl 7; abstr 14)