Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Abstract
:1. Introduction
2. Methods
2.1. Castration-Resistant Prostate Cancer
2.2. Search Strategy, Data Acquisition, and Risk of Bias
3. Current Treatments in mCRPC
3.1. Chemotherapy
3.1.1. Docetaxel
3.1.2. Cabazitaxel
3.2. Second-Generation Antiandrogens
3.2.1. Abiraterone
3.2.2. Enzalutamide
3.3. Radiopharmaceuticals
Radium-223
4. Emerging Treatments in mCRPC
4.1. DNA Repair Gene Mutations
4.1.1. PARP Inhibitors
4.1.2. Platinum-Based Chemotherapy for DNA Repair Defects
4.2. Immunotherapy
4.3. Radioisotopes
4.4. AKT Inhibitors
5. Therapeutic Sequencing in mCRPC
6. Bone-Targeted Therapy
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Therapy | Type | Study Design | Trial Name | N Patients | Trial Phase | Efficacy OS (Months) | Adverse Events G3-4 | Comments |
---|---|---|---|---|---|---|---|---|
Chemotherapy | Docetaxel | MTX + PRD vs. DOC + PRD | TAX327 | 1006 | III | 18.9 vs. 16.5 | 26% | DOC improves OS and symptoms |
Cabazitaxel | CBZ + PRD vs. MTX + PRD CBZ20 + PRD vs. CBZ25 + PRED vs. DOC | TROPIC FIRSTANA | 755 1168 | III III | 15.1 vs. 12.7 25.2 vs. 24.3 | 82% neutropenia 41.2–60.1% | CBZ improves OS after DOC-based therapy CBZ20/25 is not superior to DOC | |
Second-generation antiandrogens | Abiraterone | AB + PRD vs. Placebo + PRD AB + PRD vs. Placebo + PRD | COU/301 COU/302 | 1195 1088 | III III | 14.8 vs. 10.9 34.7 vs. 30.3 | 55% vs. 43% 48% vs. 42% | AB improves OS after DOC treatment AB improves OS in chemotherapy-naive patients |
Enzalutamide | ENZA vs. Placebo ENZA vs. Placebo | AFFIRM PREVAIL | 1199 1717 | III III | 18.4 vs. 13.6 32.4 vs. 30.2 | 45% vs. 53% 43% vs. 37% | ENZ improves OS after chemotherapy ENZ improves OS in chemotherapy-naïve patients | |
Radiopharmaceuticals | Radium-223 | Ra-223 vs. Placebo Ra-223 + AB vs. AB | ALSYMPCA ERA | 921 806 | III III | 14.9 vs. 11.3 30.7 vs. 33.3 | 56% vs. 62% 28.6% vs. 11.4% * | Ra-223 improves OS Ra-223 + AB did not improve SSE-free survival and increased bone fractures |
Therapy | Type | Study Design | Trial Name | N Patients | Trial Phase | Efficacy OS (Months) | Adverse Events G3-4 | Comments |
---|---|---|---|---|---|---|---|---|
PARP inhibitors | Olaparib | Olaparib vs. ENZA or AB | PROFOUND | 387 | III | 18.5 vs. 15.1 | 51% vs. 38% | Olaparib improves PFS, measures of response and patient-reported end points in those with alterations in genes with a role in homologous recombination repair |
Immunotherapy | Sipileucel-T | Sipileucel vs. placebo | IMPACT | 512 | III | 25.8 vs. 21.7 | 31.7% vs. 35.1% | Sipuleucel-T improves OS. No effect on time to disease progression |
Ipilimumab | RT + Ipilimumab vs. RT + Placebo Ipilimumab vs. Placebo | CA184-043 CHEMO-NAIVE | 799 602 | III III | 11.2 vs. 10.0 28.7 vs. 29.7 | 26% vs. 3% 40% vs. 6% | NO differences in OS Ipilimumab did not improve OS, but did improve PFS and PSA response | |
Atezolizumab | Atezolizumab + ENZA vs. ENZA | IMBASSADOR 250 | 759 | III | 16.6 vs. 15.2 | 54% vs. 35% | Atezolizumab did not improve OS | |
Radioisotopes | [¹⁷⁷Lu]Lu-PSMA-617 | [¹⁷⁷Lu]Lu-PSMA-617 vs. CBZ [¹⁷⁷Lu]Lu-PSMA-617 vs. Standard care | THERAP VISION | 291 1179 | II III | 65% vs. 37% * 15.3 vs. 11.3 8.7 vs. 3.4 *** | 33% vs. 53% 52.7% vs. 38% | [¹⁷⁷Lu]Lu-PSMA-617 had better PSA response and fewer toxicity than CBZ [¹⁷⁷Lu]Lu-PSMA-617 prolonged PFS and OS |
AKT inhibitors | Ipatasertib | Ipatasertib + Placebo vs. Ipatasertib + AB | IPATENTIAL 150 | 253 | II | 18.9 vs. 15.6 | 64.3%, 50.6% ** vs. 35.4% | Ipatasertib + AB showed better antitumor activity in PTEN-loss tumors |
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Henríquez, I.; Roach, M., III; Morgan, T.M.; Bossi, A.; Gómez, J.A.; Abuchaibe, O.; Couñago, F. Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC). Biomedicines 2021, 9, 1247. https://doi.org/10.3390/biomedicines9091247
Henríquez I, Roach M III, Morgan TM, Bossi A, Gómez JA, Abuchaibe O, Couñago F. Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC). Biomedicines. 2021; 9(9):1247. https://doi.org/10.3390/biomedicines9091247
Chicago/Turabian StyleHenríquez, Iván, Mack Roach, III, Todd M. Morgan, Alberto Bossi, Junior A. Gómez, Oscar Abuchaibe, and Felipe Couñago. 2021. "Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC)" Biomedicines 9, no. 9: 1247. https://doi.org/10.3390/biomedicines9091247