Truqap combination in PTEN-deficient metastatic hormone-sensitive prostate cancer demonstrated statistically significant and clinically meaningful improvement in radiographic progression-free survival in CAPItello-281 Phase III trial
First and only AKT inhibitor combination to demonstrate benefit in this specific subtype of prostate cancer
Positive high-level results from the CAPItello-281 Phase III trial showed that AstraZeneca’s Truqap (capivasertib) in combination with abiraterone and androgen deprivation therapy (ADT) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of radiographic progression-free survival (rPFS) versus abiraterone and ADT with placebo in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC).
Overall survival (OS) data were immature at the time of this analysis; however, the Truqap combination showed an early trend towards an OS improvement versus abiraterone and ADT with placebo. The trial will continue as planned to further assess OS as a key secondary endpoint.
Prostate cancer is the second most prevalent cancer in men and the fifth leading cause of male cancer death globally.1 Only one third of patients with metastatic prostate cancer survive five years after diagnosis.2 Newly diagnosed mHSPC is an aggressive form of the disease associated with poor outcomes and survival.3,4 Approximately 200,000 patients are diagnosed with mHSPC each year, and one in four have PTEN-deficient tumours.5 Patients with a tumour biomarker of PTEN deficiency have a particularly poor prognosis.6
Karim Fizazi, MD, PhD, Institut Gustave Roussy, and University of Paris Saclay in Villejuif, France, and principal investigator for the trial said: “Patients with this aggressive form of prostate cancer with tumour PTEN deficiency currently face a particularly poor prognosis, and there is an urgent need for new treatments that improve upon current therapies. The results seen with capivasertib in combination with abiraterone-prednisone and androgen deprivation therapy in the CAPItello-281 trial represent a step forward for these patients.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “These results show for the first time, that adding an AKT inhibitor to a standard-of-care therapy can provide benefit to patients with a biomarker of PTEN-deficient metastatic hormone-sensitive prostate cancer. By targeting a key driver of the disease, we have been able to improve upon current therapies and demonstrate the potential role of this combination in an area of critical unmet need. It will be important to see greater maturity in key secondary endpoints including overall survival.”
The safety profile of Truqap in combination with abiraterone and ADT in CAPItello-281 was broadly consistent with the known profile of each medicine.
Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.
References
1. Bray F, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. doi: 10.3322/caac.21834.
2. Chowdhury S, et al. Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry. Target Oncol. 2020;15(3):301-315.
3. Hussain M, et al. Metastatic Hormone-Sensitive Prostate Cancer and Combination Treatment Outcomes A Review. JAMA Oncol. 2024;10(6):807-820.
4. American Society of Clinical Oncology Educational Book. Metastatic Hormone-Sensitive Prostate Cancer: Toward an Era of Adaptive and Personalized Treatment. Available at: https://ascopubs.org/doi/pdf/10.1200/EDBK_390166. Accessed November 2024.
5. Cerner CancerMPact database. Accessed November 2024.
6. Cuzick J et al. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. Br J Cancer. 2013;108(12):2582-2589.