The past year has witnessed the U.S. Food and Drug Administration (FDA) approval of a number of drugs for treatment of patients with metastatic castrate-resistant prostate cancer or castrate-sensitive prostate cancer.
Castrate-Resistant Prostate Cancer
Olaparib: On May 19, 2020, olaparib (Lynparza) was approved by the FDA to treat deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who experienced disease progression after treatment with enzalutamide or abiraterone. Approval was based on findings from the multicenter, open-label, phase III PROfound trial.2
The FDA simultaneously approved the FoundationOne CDx assay for selection of patients with metastatic castration-resistant prostate cancer carrying homologous recombination repair gene alterations and the BRACAnalysis CDx test for selection of patients with metastatic castration-resistant prostate cancer carrying germline BRCA1/2 alterations as companion diagnostic devices for treatment with olaparib in this setting.
Like rucaparib, olaparib is an inhibitor of PARP enzymes. In the current indication, the recommended dosage of olaparib is 300 mg twice daily, with treatment continuing until disease progression or unacceptable toxicity.
Rucaparib: On May 15, 2020, rucaparib (Rubraca) was granted accelerated approval for deleterious BRCA mutation–associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor–directed therapy and taxane-based chemotherapy. Approval was supported by findings in the ongoing multicenter phase II TRITON2 study.1
Rucaparib is an inhibitor of the PARP1, PARP2, and PARP3 enzymes, which play a role in DNA repair. The recommended dose of rucaparib is 600 mg twice daily, with or without food. Treatment should be continued until disease progression or unacceptable toxicity.
Darolutamide: On July 30, 2019, darolutamide (Nubeqa) was approved for nonmetastatic castration-resistant prostate cancer. Approval was based on findings in the double-blind phase III ARAMIS trial.3
Darolutamide is an androgen-receptor inhibitor and has also functioned as a progesterone receptor antagonist in vitro. The recommended dosage of darolutamide is 600 mg orally twice daily.
Metastatic Castration-Sensitive Prostate Cancer
Enzalutamide: On December 16, 2019, enzalutamide (Xtandi) was approved for metastatic castration-sensitive prostate cancer. The current approval was based on findings from the phase III double-blind ARCHES trial.4
Enzalutamide is an androgen-receptor inhibitor that acts at a number of steps in the androgen receptor–signaling pathway. The recommended dose for the current indication is 160 mg once daily.
Apalutamide: On September 17, 2019, apalutamide (Erleada) was approved for metastatic castration-sensitive prostate cancer. The approval was based on overall survival and radiographic progression-free survival findings in the phase III double-blind TITAN trial.5
Apalutamide is an androgen-receptor inhibitor that binds directly to the ligand-binding domain of the androgen receptor. The recommended dose of apalutamide is 240 mg once daily.
1. Abida W, et al: Ann Oncol 30:v327-v328, 2019.
2. de Bono J, et al: N Engl J Med 382:2091-2102, 2020.
3. Fizazi K, et al: N Engl J Med 380:1235-1246, 2019.
4. Armstrong AJ, et al: J Clin Oncol 37:2974-2986, 2019.
5. Chi KN, et al: N Engl J Med 381:13-24, 2019.