William K. Oh, MD, prepared useful Practice Aids pertaining to prostate cancer for this CME/MOC activity titled "Chair’s Take on Innovation in Prostate Cancer: Thoughts on New Evidence." For the full presentation, monograph, complete CME/MOC information, and to apply for credit, please visit us at https://bit.ly/3cI9UQk. CME/MOC credit will be available until June 21, 2021.

1. Access the activity, “Chair’s Take on Innovation in Prostate Cancer: Thoughts on New Evidence” at
PeerView.com/UPY40
AR-Targeted Agents in Prostate Cancer
PRACTICE AID
Indication
• Patients with metastatic CSPC and nmCRPC
Dosing
• 240 mg orally once daily; swallow whole with
or without food
• Should also receive a GnRH analog concurrently
or have had a bilateral orchiectomy
AEs in ≥10% of Patients
• Fatigue, arthralgia, rash, decreased appetite,
falls, weight decrease, hypertension, hot flush,
diarrhea, and fracture
Indication
• Patients with CRPC and metastatic CSPC
AEs in ≥10% of Patients
• Asthenia/fatigue, back pain, hot flush,
constipation, arthralgia, decreased appetite,
diarrhea, and hypertension
Dosing
• 160 mg orally once daily; swallow whole with
or without food
• Should also receive a GnRH analog concurrently
or have had a bilateral orchiectomy
Apalutamide1 Enzalutamide3
Darolutamide2
Indication
• Patients with nmCRPC
Dosing
• Two 300-mg tablets administered orally twice
daily; taken with food
• Should also receive a GnRH analog concurrently
or have had a bilateral orchiectomy
AEs in ≥2% of Patients
• Fatigue, pain in extremity, and rash
Indication, Dosing, and AEs in AR-Targeted Agents for Prostate Cancer

2. Access the activity, “Chair’s Take on Innovation in Prostate Cancer: Thoughts on New Evidence” at
PeerView.com/UPY40
AR-Targeted Agents in Prostate Cancer
PRACTICE AID
a
Final analysis after 254 deaths (15.5% darolutamide and 19.1% placebo).
b
OS not reached in apalutamide or placebo groups as of May 15, 2019.
ADT: androgen deprivation therapy; AE: adverse event; AR: androgen receptor; CRPC: castration-resistant prostate cancer; CSPC: castration-sensitive prostate cancer; CT: computed tomography; ECOG PS: Eastern Cooperative Oncology Group Performance Status; GnRH: gonadotropin-
releasing hormone; HSPC: hormone-sensitive prostate cancer; MFS: metastasis-free survival; mHSPC: metastatic hormone-sensitive prostate cancer; nmCRPC: nonmetastatic castration-resistant prostate cancer; PSA: prostate-specific antigen; PSADT: prostate-specific antigen doubling
time; rPFS: radiographic progression-free survival.
1. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/ERLEADA-pi.pdf. 2. http://labeling.bayerhealthcare.com/html/products/pi/Nubeqa_PI.pdf. 3. https://www.astellas.us/docs/12A005-ENZ-WPI.PDF. 4. Small EJ et al. Ann Oncol. 2019;30:1813-
1820. 5. Smith MR et al. N Engl J Med. 2018;378:1408-1418. 6. Hussain M et al. N Engl J Med. 2018;378:2465-2474. 7. Fizazi K et al. American Society of Clinical Oncology 2019 Genitourinary Cancers Symposium (ASCO GU 2019). Abstract 140. 8. Small EJ et al. 2020 ASCO Virtual Scientific
Program (ASCO 2020). Abstract 5516. 9. Fizazi K et al. ASCO 2020. Abstract 5514. 10. Sternberg CN et al. ASCO 2020. Abstract 5515. 11. Sternberg CN et al. N Engl J Med. 2020;382:2197-2206. 12. Chi KN et al. N Engl J Med. 2019;381:13-24. 13. https://clinicaltrials.gov/ct2/show/NCT02489318.
14. https://clinicaltrials.gov/ct2/show/NCT02799602. 15. https://clinicaltrials.gov/ct2/show/NCT02677896. 16. Armstrong AJ et al. ASCO GU 2019. Abstract 687. 17. https://www.ascopost.com/issues/april-10-2019-supplement-conference-highlights-gugi-2019/interim-analysis-of-the-
arches-trial.
• nmCRPC
• Rising PSA despite castrate testosterone level (≤50 ng/dL)
• PSADT ≤10 mo
Apalutamide
40.5 mo
Placebo
16.2 mo
1° endpoint:
MFS
Median OS, mo
vs
MFS
Apalutamide
73.9 mo
Placebo
59.9 mo
mOS
SPARTAN4,5,8
Apalutamide
+ ADT
Placebo
+ ADT
• nmCRPC
• Rising PSA despite castrate testosterone level (≤50 ng/dL)
• Baseline PSA ≥2 ng/mL; PSADT ≤10 mo
Enzalutamide
36.6 mo
Placebo
14.7 mo
1° endpoint:
MFS
Median OS, mo
vs
MFS
Enzalutamide
67.0 mo
Placebo
56.3 mo
mOS
PROSPER6,10,11
Enzalutamide
+ ADT
Placebo
+ ADT
• nmCRPC
• Castrate level of serum testosterone (<50 ng/dL)
• Baseline PSA ≥2 ng/mL; PSADT ≤10 mo
1° endpoint:
MFS
Median OS, moa
vs
Darolutamide
40.4 mo
Placebo
18.4 mo
Darolutamide
NR
Placebo
NR
MFS
mOS
ARAMIS7,9
Darolutamide
+ ADT
Placebo
+ ADT
AR-Targeted Agents in Nonmetastatic CRPC
• mCSPC
• Newly diagnosed or previously treated
• ECOG PS 0 or 1
Apalutamide
Not Reached
Enzalutamide
Not Reached
Placebo
21.1 mo
1° endpoint:
Median rPFS
and OSb
vs
rPFS
TITAN12,13
Apalutamide
+ ADT
Placebo
+ ADT
• mCSPC (confirmed by bone scan, CT, or MRI)
• ECOG PS 0 or 1
Placebo
19.45 mo
1° endpoint:
rPFS
vs
rPFS
ARCHES15-17
Enzalutamide
+ ADT
Placebo
+ ADT
• mCSPC
• Newly diagnosed
• ECOG PS 0 or 1
1° endpoint:
OS
vs
ARASENS14
Darolutamide
+ ADT
+ docetaxel
Placebo
+ ADT
+ docetaxel
AR-Targeted Agents in Metastatic CSPC
Ongoing; primary completion date:
August 2022

3. Novel Approaches in
Advanced Prostate Cancer
PRACTICE AID
Access the activity, “Chair’s Take on Innovation in Prostate Cancer: Thoughts on New Evidence” at
PeerView.com/UPY40
Galahad (NCT02854436); Phase 2
RESULTS
• mCRPC previously treated
with ≥1 line of taxane-based
chemo; received ≥1 line of
AR-targeted therapy
• DDR anomalies
• Planned N = 301
N = 81 (46 with BRCA1/2
and 35 with non-BRCA1/2)
ORR
41% in BRCA1/2; 9% in non-BRCA1/2
Composite response rate
63% in BRCA1/2; 17% in BRCA1/2
PSA response rate
50% in BRCA1/2; 3% in non-BRCA1/2
Niraparib 1° endpoint: ORR
Selected Ongoing Trials of PARP Inhibitors1-8
TOPARP-B (NCT01682772);
Multi-stage phase 2 design
RESULTS
• mCRPC; ongoing ADT or prior bilateral
orchiectomy
• Previously treated with 1 or 2 lines of
taxane-based chemo and/or AR-directed
therapy
• N = 98
RR; evaluable N = 98
Endpoints:
ORR 54% in 400 mg, 37% in 300 mg
olaparib cohort
Median PFS: 5.4 mo
Primary endpoint per gene subgroup:
BRCA1/2: 80%
PALB2: 57%
Olaparib 1° endpoint: RR
ATM: 37%
CDK12: 25%
Olaparib
+ abiraterone
Placebo
+ abiraterone
vs
1° endpoint:
rPFS
NCT01972217; Phase 2
RESULTS
• mCRPC
• ECOG PS 0 or 1
• ≤2 prior lines of chemo
• Planned N = 158
rPFS; evaluable N = 142
Olaparib: 13.8 mo
Placebo: 8.2 mo
HR = 0.65; P = .034
PROfound (NCT02987543); Phase 3
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• Previously treated with AR-targeted therapy
• N = 387
RESULTS
Olaparib: median rPFS 7.39 mo
Physician's choice: rPFS 3.55 mo
HR = 0.34 (95% CI, 0.25-0.47);
P < .0001
1° endpoint:
rPFSvs
Enzalutamide
or abiraterone
Olaparib
FDA Approved
May 20207,a
TRITON2 (NCT02952534); Phase 2
• mCRPC; progression on AR-directed therapy and1 prior taxane;
HRR gene aberration
• No prior PARP inhibitor, mitoxantrone, cyclophosphamide,
or platinum-based chemo
• Planned N = 360
RESULTS
ORR
BRCA1/2 pts, n = 57; 43.9%
PSA response
BRCA1/2 pts, n = 57; 59.6%
Rucaparib 1° endpoints: ORR, PSA response
FDA Approved
May 20208,b

4. Novel Approaches in
Advanced Prostate Cancer
PRACTICE AID
Access the activity, “Chair’s Take on Innovation in Prostate Cancer: Thoughts on New Evidence” at
PeerView.com/UPY40
Talazoparib
+ enzalutamide
vs 1° endpoints:
dose, rPFS
Placebo
+ enzalutamide
Selected Ongoing Trials of PARP Inhibitors1
(Cont’d)
PROpel (NCT03732820); Phase 3
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• ECOG PS 0 or 1
• Assessment of HRR gene aberrations
• Planned N = 720
vs 1° endpoint:
rPFS
Placebo
+ abiraterone
Olaparib
+ abiraterone
vs 1° endpoint:
rPFS
Placebo
+ abiraterone
Niraparib
+ abiraterone
MAGNITUDE (NCT03748641); Phase 3
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• Planned N = 1,000
TRITON3 (NCT02975934); Phase 3
• mCRPC previously treated with 1 next-generation
AR-targeted therapy
• Deleterious mutation in BRCA1/2 or ATM
• Planned N = 400
vs
1° endpoint:
rPFS
Abiraterone
or enzalutamide
or docetaxel
vs
Rucaparib
Avelumab +
bempegaldesleukin
Recruiting Recruiting Recruiting
Recruiting Recruiting
Rucaparib 1° endpoint:
ORR
1° endpoints:
confirmed OR,
PSA response, DLTs
LODESTAR (NCT04171700); Phase 2, open-label
• Unresectable, locally advanced, or metastatic solid tumor and relapsed/progressive disease
• At least 1 prior line of therapy extending OS or SOC therapy for advanced disease
• mCRPC with BRCA1/2 mutations
• ECOG PS 0 or 1
• Planned N = 220 (with solid tumors)
Avelumab + bempegaldesleukin (NKTR-214) + talazoparib or
enzalutamide (NCT04052204); Phase 2, open-label
• mCRPC
• ECOG PS 0 or 1
• Planned N = 160
• Cohort A: deleterious mutations in BRACA1/2
• Cohort B: non-BRACA1/2 mutations
Active,
not
recruiting
Recruiting
Talazoparib 1° endpoint:
ORR
TALAPRO-1 (NCT03148795); Phase 2, open-label
• mCRPC; metastatic disease in bone
• Assessment of DDR mutation status
• ECOG PS 0 to 2
• Planned N = 100
TALAPRO-2 (NCT03395197); Phase 3
• mCRPC; metastatic disease
in bone
• Assessment of DDR mutation status
• ECOG PS 0 or 1
• Planned N = 1,037
RESULTS
Confirmed ORR:9,c
28.0%
Composite response:9
51.2%
Avelumab
+ bempegaldesleukin
+ talazoparib
or enzalutamide

5. Novel Approaches in
Advanced Prostate Cancer
PRACTICE AID
Access the activity, “Chair’s Take on Innovation in Prostate Cancer: Thoughts on New Evidence” at
PeerView.com/UPY40
a
In May 2020, the FDA approved olaparib for adult patients with deleterious/suspected deleterious germline/somatic HRR gene-mutated mCRPC following progression on enzalutamide of abiraterone. b
In May 2020, the FDA approved rucaparib for patients with deleterious germline/
somatic BRCA mutation-associated mCRPC previously treated with AR-directed therapy and a taxane-based chemotherapy. c
In patients who received talazoparib for ≥16 weeks.
ADT: androgen deprivation therapy; AR: androgen receptor; DDR: DNA damage repair; DLT: dose-limiting toxicity; ECOG PS: Eastern Cooperative Oncology Group Performance Status; HRD: homologous recombination deficiency; HRR: homologous recombination repair;
mCRPC: metastatic castration-resistant prostate cancer; OR: overall response; ORR: objective response rate; PARP: poly (ADP-ribose) polymerase; PD-1: programmed cell death protein 1; PD-L1: programmed death ligand 1; PSA: prostate-specific antigen; rPFS: radiographic
progression-free survival ; RR: response rate.
1. https://clinicaltrials.gov. 2. Mateo J et al. 2019 American Society of Clinical Oncology Annual Meeting (ASCO 2019). Abstract 5005. 3. Clarke N et al. Lancet Oncol. 2018;19:975-986. 4. de Bono J et al. N Engl J Med. 2020;382:2091-2102. 5. Abida W et al. ESMO 2019. Abstract 846PD.
6. Smith MR et al. American Society of Clinical Oncology 2019 Genitourinary Cancers Symposium (ASCO GU 2019). Abstract 202. 7. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-olaparib-hrr-gene-mutated-metastatic-castration-resistant-prostate-cancer. 8.
https://www.fda.gov/drugs/fda-grants-accelerated-approval-rucaparib-brca-mutated-metastatic-castration-resistant-prostate. 9. De Bono JS et al.2020 ASCO Virtual Scientific Program (ASCO 2020). Abstract 5566. 10. Karzai F et al. J Immunother Cancer. 2018;6:141. 11. Yu EY et al. J Clin
Oncol. 2020;38 (suppl; abstr 5544). 12. Sridhar SS et al. J Clin Oncol. 2020;38 (suppl; abstr 5550). 13. Conter HJ et al. J Clin Oncol. 2020;38 (suppl; abstr 5545).
Selected Ongoing Trials of PARP Inhibitors Combined With PD-1/PD-L1 Inhibitors1,7-10
JAVELIN PARP MEDLEY
(NCT03330405); Phase 2
• Locally advanced or mCRPC
• Primary or metastatic tumor biopsy
• ECOG PS 0 or 1
• Planned N = 242
CheckMate -9KD (NCT03338790);
Phase 2
• mCRPC; ongoing ADT
• Plasma and fresh or
archival tumor tissue
• ECOG PS 0-1
CheckMate -7DX
(NCT04100018); Phase 3
• Stage IV prostate cancer
• ECOG PS 0-1
• Ongoing ADT
• Chemotherapy-naïve and received 1-2 prior
second-generation hormonal therapies
Active,
no
recruiting
Recruiting Recruiting
1° endpoints:
DLTs, OR
1° endpoints:
safety, ORR,
composite RR
• HRD status (must be
available before tx
arm assignment)
• Planned N = 330
1° endpoints:
ORR, PSA response
• Planned
N = 984
1° endpoints:
rPFS, OS
Nivolumab or placebo
+ docetaxel in CRPC
Avelumab +
talazoparib
Nivolumab + rucaparib or
docetaxel or enzalutamide
KEYNOTE-365 (NCT02861573);
Phase 1b/211-13
• mCRPC; ongoing ADT
• Tissue biopsy from site not previously irradiated
• Planned N = 400
QUEST (NCT03431350);
Phase 1/2
• mCRPC
• DDR gene anomalies
• Prior novel AR-targeted therapy
• Planned N = 80
NCT02484404;
Phase 2 (prostate cohort)
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• ECOG PS 0 or 1; previously treated with enzalutamide
and/or abiraterone
• Planned N = 384
RecruitingRecruiting Recruiting
Niraparib
+ cetrelimab
RESULTS
PSA response
Pembro + olaparib, n = 84; 9%
Pembro + docetaxel, n = 104; 28%
Pembro + enzalutamide, n = 102; 22%
1° endpoint:
PSA response
Pembrolizumab + olaparib
or docetaxel/prednisone or
enzalutamide or abiraterone
1° endpoints:
dose, safety
Durvalumab
+ olaparib
RESULTS
rPFS; evaluable N = 17
Durvalumab + olaparib: 16.1 mo
12-month rPFS: 51.5%
9/17 (53%) patients had a radiographic and/or
PSA response