Robert Dreicer, MD, MS, MACP, FASCO, Philip Kantoff, MD, Charles J. Ryan, MD, and Evan Y. Yu, MD, prepared useful practice aids pertaining to prostate cancer for this CME activity titled "New Concepts in Prostate Cancer Care: What Oncologists Need to Know to Optimize Patient Outcomes.” For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2FLnDrG. CME credit will be available until July 15, 2020.

1. AR-Targeted Agents in Prostate Cancer
Access the activity, “New Concepts in Prostate Cancer Care: What Oncologists Need to Know to Optimize Patient Outcomes” at
PeerView.com/NXS40.
PRACTICE AID
Apalutamide
Enzalutamide
Darolutamide
Common AEs
• Fatigue, asthenia,
dizziness, bone
fracture, falls,
hypertension,
and weight
decreasevs 1° endpoint: MFS
40.4 mo
18.4 mo
Darolutamide
Placebo
MFS
• nmCRPC
• Castrate testosterone level
• Baseline PSA ≥2 ng/mL; PSADT ≤10 mo
ARAMIS
Indication
• Male adult patients
with nonmetastatic
CRPC
• nmCRPC
• Rising PSA despite castrate testosterone
level (≤50 ng/dL)
• PSADT ≤10 mo
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
40.5 mo
16.2 mo
Apalutamide
1° endpoint: MFSvs Placebo
AEs in ≥10% of patients
• Fatigue, arthralgia, rash, decreased
appetite, peripheral edema, falls,
fractures, weight decrease,
hypertension, hot flush, diarrhea,
and nausea
MFSSPARTAN
Apalutamide
+ ADT
Placebo
+ ADT
Darolutamide
+ ADT
Indication
• Male adult patients
with nonmetastatic
and metastatic CRPC
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
AEs in ≥10% of patients
• Asthenia, fatigue, decreased appetite,
hot flush, arthralgia, dizziness, vertigo,
hypertension, headache, and
weight decrease
vs 1° endpoint: MFS
36.6 mo
14.7 mo
Enzalutamide
Placebo
MFS
• nmCRPC
• Rising PSA despite castrate testosterone
level (≤50 ng/dL)
• Baseline PSA ≥2 ng/mL; PSADT ≤10 mo
PROSPER
Enzalutamide
+ ADT
Placebo
+ ADT
Placebo
+ ADT
AR-Targeted Agents in Nonmetastatic CRPC1-6

2. AR-Targeted Agents in Prostate Cancer
Access the activity, “New Concepts in Prostate Cancer Care: What Oncologists Need to Know to Optimize Patient Outcomes” at
PeerView.com/NXS40.
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
a
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; 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; MRI: magnetic resonance imaging; nmCRPC: nonmetastatic castration-resistant prostate cancer; PSA: prostate-specific antigen; PSADT: prostate-specific antigen doubling time;
rPFS: radiographic progression-free survival.
1. Erleada (apalutamide) Prescribing Information. https:// http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/ERLEADA-pi.pdf. Accessed May 15, 2019. 2. Xtandi (enzalutamide) Prescribing Information. https://www.astellas.us/docs/12A005-
ENZ-WPI.PDF. Accessed May 15, 2019. 3. Small EJ et al. 2018 Genitourinary Cancers Symposium (ASCO GU 2018). Abstract 161. 4. Smith MR et al. N Engl J Med. 2018;378:1408-1418. 5. Hussain M et al. ASCO GU 2018. Abstract 3. 6. https://clinicaltrials.gov/ct2/show/NCT02200614. Accessed
May 15, 2019. 7. https://clinicaltrials.gov/ct2/show/NCT02489318. Accessed May 15, 2019. 8. Chi KN et al. 2019 American Society of Clinical Oncology Annual Meeting (ASCO 2019). Abstract 5006. 9. https://clinicaltrials.gov/ct2/show/NCT02677896. Accessed May 15, 2019. 10. Armstrong
AJ et al. ASCO GU 2019. Abstract 687. 11. https://www.ascopost.com/issues/april-10-2019-supplement-conference-highlights-gugi-2019/interim-analysis-of-the-arches-trial/. Accessed May 15, 2019. 12. https://clinicaltrials.gov/ct2/show/NCT02799602. Accessed May 15, 2019.
AR-Targeted Agents in Metastatic HSPC7-12
Apalutamide
Enzalutamide
Darolutamide vs
1° endpoint: OS
• mHSPC
• Newly diagnosed
• ECOG PS 0 or 1
ARASENS
• mHSPC
• Newly diagnosed or previously treated
• ECOG PS 0 or 1
Not
reached
22.1 mo
Apalutamide
1° endpoints:
rPFS and OSavs Placebo
rPFSTITAN
Apalutamide
+ ADT
Placebo
+ ADT
Darolutamide
+ ADT
+ docetaxel
vs 1° endpoint: rPFS
• mHSPC (confirmed by bone scan, CT,
or MRI)
• ECOG PS 0 or 1
ARCHES
Enzalutamide
+ ADT
Placebo
+ ADT
Placebo
+ ADT
+ docetaxel
Rates of Grade 3/4 AEs
• 42% in apalutamide
group and 41% in
placebo group
Not
reached
19.45
Enzalutamide
Placebo
rPFS AEs in ≥5% of patients
• Fatigue, hot flush,
arthralgia, back pain,
hypertension, nausea,
musculoskeletal pain,
dizziness, and fractures
Ongoing;
primary
completion date:
August 2022

3. Novel Approaches in
Advanced Prostate Cancer
Access the activity, “New Concepts in Prostate Cancer Care: What Oncologists Need to Know to Optimize Patient Outcomes” at
PeerView.com/NXS40.
PRACTICE AID
Selected Ongoing Trials of Single-Agent PARP Inhibitors1-4
TOPARP-A (NCT01682772); Phase 2
RESULTS
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• Previously treated with 1 or 2 lines of taxane-based
chemo and/or AR-directed therapy
• Planned N = 89
PROfound (NCT02987543); Phase 3
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• Previously treated with AR-targeted therapy
• Planned N = 340
RR; evaluable N = 49
Patients with DDR: 89%
Patients without DDR: 6%
Olaparib Olaparib
Active,
not
recruiting
vs1° endpoint: RR 1° endpoint: rPFS
Enzalutamide
or abiraterone
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
PROpel (NCT03732820); Phase 3
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• ECOG PS 0 or 1
• Assessment of HRR gene aberrations
• Planned N = 720
Olaparib
+ abiraterone
Placebo
+ abiraterone
vs vs1° endpoint: rPFS 1° endpoint: rPFS
Placebo
+ abiraterone
Olaparib
+ abiraterone
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
MAGNITUDE (NCT03748641); Phase 3
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• Planned N = 1,000
ORR; evaluable N = 50
BRCA1/2, n = 29: 38%
Non-BRCA1/2, n = 21: 13%
Niraparib vs1° endpoint: ORR 1° endpoint: rPFS
Placebo
+ abiraterone
Niraparib
+ abiraterone
TRITON2 (NCT02952534); Phase 2
RESULTS
• mCRPC; progression on AR-directed therapy and 1 prior
taxane; HRR gene aberration
• No prior PARP inhibitor, mitoxantrone, cyclophosphamide,
or platinum-based chemo
• Planned N = 360
TRITON3 (NCT02975934); Phase 3
• mCRPC previously treated with 1 next-generation
AR-targeted therapy
• Deleterious mutation in BRCA1/2 or ATM
• Planned N = 400
ORR
(BRCA1/2 pts, n = 25): 44%
PSA response
(all pts, n = 45): 51%
Rucaparib vs1° endpoints: ORR, PSA response 1° endpoint: rPFS
Abiraterone
or enzalutamide
or docetaxel
Rucaparib
Recruiting
Recruiting
Recruiting

4. Novel Approaches in
Advanced Prostate Cancer
PRACTICE AID
This Practice Aid has been provided as a quick reference to help learners apply the information to their daily practice and care of patients.
ADT: androgen deprivation therapy; AR: androgen receptor; DDR: DNA damage repair; DLT: dose-limiting toxicity; ECOG PS: Eastern Cooperative Oncology Group Performance Status; 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; PFS: progression-free survival; PSA: prostate-specific antigen; rPFS: radiographic progression-free survival ; RR: response rate.
1. https://clinicaltrials.gov. Accessed May 15, 2019. 2. Mateo J et al. N Engl J Med. 2015;373:1697-1708. 3. Clarke N et al. Lancet Oncol. 2018;19:975-986. 4. Smith MR et al. 2019 Genitourinary Cancers Symposium (ASCO GU 2019). Abstract 202. 5. Yu E et al. ASCO GU 2019. Abstract 145.
6. Massard C et al. ASCO GU 2019. Abstract 170. 7. Fong PCC et al. ASCO GU 2019. Abstract 171.
Access the activity, “New Concepts in Prostate Cancer Care: What Oncologists Need to Know to Optimize Patient Outcomes” at
PeerView.com/NXS40.
TALAPRO-2 (NCT03395197); Phase 3
• mCRPC; metastatic disease in bone
• Assessment of DDR mutation status
• ECOG PS 0 or 1
• Planned N = 872
Talazoparib
+ enzalutamide vs 1° endpoints: dose, rPFSPlacebo
+ enzalutamide
Pembrolizumab + olaparib
or docetaxel/prednisone
or enzalutamide or abiraterone
Durvalumab
+ olaparib or cediranib
or olaparib + cediranib
KEYNOTE-365 (NCT02861573); Phase 1b/2
RESULTS
• mCRPC; ongoing ADT
• Tissue biopsy from site not previously irradiated
• Planned N = 400
NCT02484404; Phase 1/2
• mCRPC; ongoing ADT or prior bilateral orchiectomy
• ECOG PS 0 or 1; previously treated with enzalutamide
and/or abiraterone
• Planned N = 384
PSA response
Pembro + olaparib, n = 41: 12%
Pembro + docetaxel, n = 72: 31%
Pembro + enzalutamide, n = 69: 26%
1° endpoint: PSA response 1° endpoints: dose, safety
Recruiting
JAVELIN PARP MEDLEY (NCT03330405); Phase 2
• Locally advanced or mCRPC
• Primary or metastatic tumor biopsy
• ECOG PS 0 or 1
• Planned N = 242
1° endpoints: DLTs, ORAvelumab + talazoparib
Recruiting
Nivolumab + rucaparib
or docetaxel or enzalutamide
Niraparib + cetrelimab
or abiraterone
QUEST (NCT03431350); Phase 1/2
• mCRPC
• DDR gene anomalies
• Prior novel AR-targeted therapy
• Planned N = 150
1° endpoints: safety, ORR,
composite RR
Recruiting
CheckMate 9KD (NCT03338790); Phase 2
• mCRPC; ongoing ADT
• Plasma and fresh or archival tumor tissue
• Planned N = 330
1° endpoints: ORR,
PSA response
Recruiting
Recruiting
Selected Ongoing Trials
of Single-Agent PARP Inhibitors1-4
(Cont’d)
Selected Ongoing Trials of PARP Inhibitors Combined With PD-1/PD-L1 Inhibitors1,5-7