Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID)
| العنوان: | Pan-AKT Inhibitor Capivasertib With Docetaxel and Prednisolone in Metastatic Castration-Resistant Prostate Cancer: A Randomized, Placebo-Controlled Phase II Trial (ProCAID) |
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| المؤلفون: | Gareth Griffiths, Satinder Jagdev, Christine Stephens, Amit Bahl, Simon J. Crabb, Charlotte Westbury, Michelle Light, Satish Kumar, Ellice Marwood, Denise Dunkley, Carolina Salinas-Souza, Tony Elliott, Angus Robinson, Santhanam Sundar, Emily C. Shaw, Josh Northey, Amy Whitehead, Karen Martin, Alison Birtle, Robert Jones, Nichola Downs, Sam Wilding, Claire Rooney, Vincent Khoo |
| المصدر: | Journal of Clinical Oncology |
| بيانات النشر: | American Society of Clinical Oncology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Time Factors, Prednisolone, Docetaxel, Akt inhibitor, Castration resistant, Placebo, Genitourinary Cancer, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Double-Blind Method, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pyrroles, Neoplasm Metastasis, Protein Kinase Inhibitors, Aged, Aged, 80 and over, business.industry, ORIGINAL REPORTS, Middle Aged, medicine.disease, Preclinical data, Progression-Free Survival, United Kingdom, Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, Pyrimidines, 030220 oncology & carcinogenesis, Disease Progression, business, Proto-Oncogene Proteins c-akt, medicine.drug |
| الوصف: | PURPOSE Capivasertib is a pan-AKT inhibitor. Preclinical data indicate activity in metastatic castration-resistant prostate cancer (mCRPC) and synergism with docetaxel. PATIENTS AND METHODS ProCAID was a placebo controlled randomized phase II trial in mCRPC. Patients received up to ten 21-day cycles of docetaxel (75 mg/m2 intravenous, day 1) and prednisolone (5 mg twice daily, oral, day 1-21) and were randomly assigned (1:1) to oral capivasertib (320 mg twice daily, 4 days on/3 days off, from day 2 each cycle), or placebo, until disease progression. Treatment allocation used minimization factors: bone metastases; visceral metastases; investigational site; and prior abiraterone or enzalutamide. The primary objective, by intention to treat, determined if the addition of capivasertib prolonged a composite progression-free survival (cPFS) end point that included prostate-specific antigen progression events. cPFS and overall survival (OS) were also assessed by composite biomarker subgroup for PI3K/AKT/PTEN pathway activation status. RESULTS One hundred and fifty patients were enrolled. Median cPFS was 7.03 (95% CI, 6.28 to 8.25) and 6.70 months (95% CI, 5.52 to 7.36) with capivasertib and placebo respectively (hazard ratio [HR], 0.92; 80% CI, 0.73 to 1.16; one-sided P = .32). Median OS was 31.15 (95% CI, 20.07 to not reached) and 20.27 months (95% CI, 17.51 to 24.18), respectively (HR, 0.54; 95% CI, 0.34 to 0.88; two-sided P = .01). cPFS and OS results were consistent irrespective of PI3K/AKT/PTEN pathway activation status. Grade III-IV adverse events were equivalent between arms (62.2%). The most common adverse events of any grade deemed related to capivasertib were diarrhea, fatigue, nausea, and rash. CONCLUSION The addition of capivasertib to chemotherapy did not extend cPFS in mCRPC irrespective of PI3K/AKT/PTEN pathway activation status. The observed OS result (a secondary end point) will require prospective validation in future studies to address potential for bias. |
| وصف الملف: | application/pdf; text |
| اللغة: | English |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::534c54b0c47551bca3bde76fa36a8bb0Test http://europepmc.org/articles/PMC8078455Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....534c54b0c47551bca3bde76fa36a8bb0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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