megan may, pharm.d., bcop oncology clinical pharmacy ...s3.proce.com/res/pdf/794.pdf · 3 nelson...
Post on 21-Sep-2020
4 Views
Preview:
TRANSCRIPT
1
Megan May, Pharm.D., BCOPOncology Clinical Pharmacy SpecialistBaptist Health Lexington
Describe the etiology and pathophysiology of prostate cancer
Explain the mechanism of action of available therapeutics for prostate cancer
Outline the efficacy and safety of treatment options for prostate cancer
Explain how to evaluate the appropriate selection of therapy for specific prostate cancer patients
2
CDC Website. Expected New Cancer Cases and Deaths in 2010. https://www.cdc.gov/cancer/dcpc/research/articles/cancer_2020_incidence.htm
Prostate Cancer Incidence
Hormonal Testosterone is a growth signal to the prostate
Genetic Mendelian inheritance of a rare, autosomal
dominant allele Inherited gene mutations BRCA1, BRCA2, and HOXB13
Prostatic intraepithelial neoplasia (PIN)
3
Nelson WG, et al. N Engl J Med. 2003;349:366-81.Hoffman RM. N Engl J Med. 2011:1-7.
Prostate Cancer
Race
Aging
HormonesDiet
Family History
Digital Rectal Exam (DRE) Historical standard
Prostate-Specific Antigen (PSA) Test Measures the level of free and bound PSA in
the blood Cut-off point: 4 ng/mL
U.S. Preventive Services Task Force: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening1Hoffman RM. N Engl J Med. 2011:1-7.
4
Controversy over recommended screening for prostate cancer in men over 70 years old
Screening and treatment for prostate cancer can cause harm
Screening most benefits men 55-69 years old
U.S. Preventive Services Task Force: https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening1Hoffman RM. N Engl J Med. 2011:1-7.
Low risk of prostate cancer (n = 18,882) Randomized to receive finasteride 5mg PO
daily or placebo
Thompson IM, et al. NEJM 2003;349:215‐224.Thompson IM, et al. NEJM 2013;369:603-610
Primary 2003 Report Updated 2013 Report
Prostate-Cancer Grade
Relative Risk (95% CI)
P value Relative Risk (95% CI)
P value
Any Grade 0.75 (0.69-0.81) <0.001 0.70 (0.65-0.76) <0.001
Low Grade 0.62 (0.56-0.68) <0.001 0.57 (0.52-0.63) <0.001
High Grade 1.27 (1.07-1.50) 0.005 1.17 (1.00-1.37) 0.05
5
American Society of Clinical Oncology and the American Urological Association guidelines
Symptomatic men with a PSA ≤ 3.0 ng/mL who are regularly screened with PSA for early detection of prostate cancer may benefit from dutasteride or finasteride for 7 years
Graham L. Am Fam Physician. 2010;81(1):76-77.
Urinary hesitancy/retention Decreased force of stream of urine Hematuria Hematospermia Lower extremity edema Pelvic discomfort Bone pain Prostate gland lump
Nelson WG, et al. N Engl J Med. 2003;349:366-81.Hoffman RM. N Engl J Med. 2011:1-7.
6
DRE PSA Test Transrectal Ultrasound (TRUS) Biopsy Methods Transperineal prostate biopsy Transrectal prostate biopsy Transurethral prostate biopsy
http://www.prostate-cancer.com/prostate-cancer-treatment-overview/overview-trus.htmlHoffman RM. N Engl J Med. 2011:1-7.
Tumor growth rate Histology of 2 samples
are graded (1-5) Sum of grades =
Gleason score Range of 2-10 2: nonaggressive cancer 10: very aggressive
cancer
http://training.seer.cancer.gov/prostate/abstract-code-stage/morphology.html
7
Tumor size
Node involvement
Metastasis
Cancer grade
American Joint Committee on Cancer: Prostate Cancer Staging. 7th Edition. 2009.
Initial stage, grade, and PSA level at the time of definitive therapy
Absolute level of PSA Rate of change in the
PSA level Overall 5-year survival
rate = 98.2%
NIH SEER: Cancer Stat Facts: Prostate Cancer. https://seer.cancer.gov/statfacts/html/prost.html.
8
Tumor Factors Tumor Stage
Growth Rate
Aggressiveness
Treatment-Related Factors
Patient Factors Patient’s Age
Comorbid Conditions
Projected Life Expectancy
Recurrence Risk Initial Therapy
Very LowT1c, GS ≤ 6, PSA < 10ng/mL, < 3 positive bx cores (< 50% cancer in each core), PSA density < 0.15 ng/mL/g
Active surveillance
LowT1-T2a, GS ≤ 6, PSA < 10ng/mL
Active surveillance, radical prostatectomy, or radiation
Favorable IntermediateT2b-T2c or GS = 7 or PSA 10-20 ng/mL, and percentage of positive biopsy cores <50%
Radical prostatectomy, radiation with or without hormonal therapy
Unfavorable IntermediateT2b-T2c or GS = 7 or PSA 10-20 ng/mL
Radical prostatectomy, radiation withhormonal therapy
HighT3a-T4 or GS 8-10 or PSA ≥ 20 ng/mL
Radical prostatectomy, radiation withhormonal therapy
Sanda MG, et al. Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline.NIH: Prostate Cancer Treatment (PDQ). https://www.cancer.gov/types/prostate/hp/prostate-treatment-pdq#section/_62
9
Slow growing tumors with no symptoms
Requires frequent check-ups Conversion to treatment if disease
progression
Bill-Axelson, et al. N Engl J Med. 2005;352:1977-84.Johansson E, et al. Lancet Oncol. 2011;12(9):891-899.
Radical prostatectomy versus observation Scandinavian Prostate Cancer Group Study
Number 4 (SPCG-4) Prostate Testing for Cancer and Treatment Trial
(PIVOT) Radical prostatectomy versus radiation
versus observation Prostate Cancer Intervention versus Observation
Trial (ProtecT)Bill-Axelson, et al. N Engl J Med. 2014;370:932-942.Wilt TJ, et al. N Engl J Med. 2012;367:203-213.Hamdy FC, et al. N Engl J Med. 2016;375:1415-1424.
10
Involves removal of All or part of prostate gland Surrounding tissue Lymph nodes
Complications Early mortality Bladder contracture Urinary incontinence Impotence
http://www.prostate-cancer.com/prostatectomy/treatment-description/prostatectomy-description.html
High-powered energy used to kill cancer cells External beam radiation therapy Brachytherapy
▪ Seed implantation
Proton radiation therapy Option for non-surgical candidates Complications Painful, frequent, and urgent urination Loose and painful stools Erectile dysfunction
Slater JD. Int J Radiation Oncology. 2004:59(2):348-352.
11
Suppresses, blocks, or eliminates testosterone
Goal serum testosterone <20 ng/dL 1 month after initiation
http://chemoregimen.com/Prostate-Cancer-c-51-61.html
Surgical castration Bilateral orchiectomy
Medical castration Luteinizing hormone-releasing hormone
(LHRH) agonist or antagonist Anti-androgens
12
Surgical removal of testicles Adverse effects Infection Hot flashes Diminished libido Erectile dysfunction
May lower testosterone levels more quickly than other treatment options
http://www.upmccancercenters.com/cancer/prostate/hormoneorchtherapy.html
Acute adverse effects Tumor flare, gynecomastia, hot flashes, sexual dysfunction, edema,
injection site reactions Long term adverse effects Osteoporosis, clinical fracture, obesity, insulin resistance, lipid
alterations, increased CV eventsMedication Dosage for metastatic cancerLeuprolide (Lupron®, Eligard®) 7.5mg SQ every month
22.5mg SQ every 3 months 45mg SQ every 6 months
Goserelin (Zoladex®) 3.6mg SQ every month 10.8mg SQ every 3 months
Triptorelin (Trelstar®) 3.75mg IM every 4 weeks 11.25mg IM every 12 weeks 22.5mg IM every 24 weeks
Histrelin (Vantas®) 50mg implant surgically inserted every 12 monthsEligard [package insert]. Bridgewater, NJ: Sanofi-aventis; 2012. Vantas [package insert]. Malvern, PA: Endo Pharmaceuticals Solutions; 2004.
Zoladex [package insert]. Wilmington, DE: AstraZeneca; 1989. Trelstar [package insert]. Irvine, CA: Allergan; 2002.
13
Adverse effects Injection site reactions
Medication Dosage for metastatic cancerDegarelix (Firmagon®) LD: 240mg injection
MD: 80mg every 28 days (beginning 28 days after initial LD)
Firmagon [package insert]. Parsippany, NJ: Ferring Pharmaceuticals; 2015.
Prevent testosterone from reaching the cancer cells Adverse effects Diarrhea, gynecomastia, hot flashes, nausea/vomiting
Medication Dosage for metastatic cancerBicalutamide (Casodex®) 50mg PO daily
Flutamide (Eulexin®) 250mg PO TID
Nilutamide (Nilandron®) 300mg PO daily for 30 days then decrease to 150mg PO daily
Casodex [package insert]. Princeton, NJ: Zydus Pharmaceuticals; 2009.
Eulexin [package insert]. Kenilworth, NJ: Schering Corporation; 1999.
Nilandron [package insert]. Baudette, MN: ANI Pharmaceuticals; 2015.
14
Initiation of ADT PSA > 50 ng/mL Rapid PSA velocity Long life expectancy
Goal of treatment: palliative care
Anti-androgen withdrawal Steroids Aminoglutethamide Ketoconazole Megestol acetate
15
Prostate Cancer. London, England: Times Mirror International Publishers Ltd; 1996: 143.
Prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels
Defined as testosterone < 20 ng/dL and disease progression
1996
Mitoxantroneplus
prednisone
2004
Docetaxel plus prednisone
2010
Sipuleucel-T
2010
Cabazitaxelplus
prednisone
2011
Abirateroneplus predisone
2012
Enzalutamide
2013
Radium 223
2018
Apalutamide
16
Docetaxel (Taxotere®) 75mg/m2 IV over 1 hour every 3 weeks x 10 cyclesPrednisone 5mg PO BID
Docetaxel 30mg/m2 IV over 30 min weekly x 5 weeks then every 6 weeks x 5 cyclesPrednisone 5mg PO BID
Mitoxantrone (Novantrone®) 12mg/m2 IV over 30 min every 3 weeks x 10 cyclesPrednisone 5mg PO BID
Dagher R, et al. Clin Cancer Res. 2004,10(24):8147-8151.Tannock IF, et al. N Engl J Med. 2004,351(15):1502-1512.
Lorenzo GD, et al. Nature Reviews Clinical Oncology. 2011;8:551-561.
APC: Antigen Presenting CellsPAP: Prostatic Acid PhosphataseGM-CSF: Granulocyte Macrophage Colony-Stimulating Factor
17
Administration IV every 2 weeks for 3 doses
Available Doses Minimum of 50 million activated cells
Infusion Time 60 minutes
Dosage Adjustments No adjustments
Monitoring Infusion reactions (pre-medicate)
Storage Do not remove from insulated shipping box until administration
Black Box Warnings None
Kantoff FW. N Engl J Med. 2010:363;5:411-422.
Kantoff FW. N Engl J Med. 2010:363;5:411-422.
18
Kantoff FW. N Engl J Med. 2010:363;5:411-422.
Sipuleucel-T Placebo
Overall survival (months) 25.8 21.7
Time to progression (weeks) 14.6 14.4
PSA response 2.6% 1.3%
De Bono JS, et al. Lancet. 2010; 376:1147-1154.
Sipuleucel-T (n = 338) Placebo (n = 168)
Adverse Reaction All Grades Grade 3-5 All Grades Grade 3-5
Chills 183 (54.1%) 4 (1.2%) 21 (12.5%) 21 (12.5%)
Fatigue 132 (39.1%) 4 (1.2%) 64 (38.1%) 3 (1.8%)
Back Pain 132(39.1%) 12 (3.6%) 61 (36.3%) 8 (4.8%)
Pyrexia 99 (29.3%) 1 (0.3%) 23 (13.7%) 3 (1.8%)
Nausea 95 (28.1%) 2 (0.6%) 35 (20.8%) 0
Arthralgia 54 (16.0%) 1 (0.3%) 8 (4.8%) 0
Vomiting 33 (9.8%) 2 (0.6%) 8 (4.8%) 0
Headache 33 (9.8%) 0 6 (3.6%) 0
Anemia 25 (7.4%) 2 (2%) 5 (3.0%) 0
Limb Pain 17 (5.0%) 0 4 (2.4%) 0
19
Asymptomatic or minimally symptomatic patients with metastatic CRPC
May be considered for: Good performance status Life expectancy > 6 months No visceral disease
Kantoff FW. N Engl J Med. 2010:363;5:411-422.
De Bono JS, et al. Lancet. 2010; 376:1147-1154.Jevtana [package insert]. Bridgewater, NJ: Sanofi-aventis; 2010.
Microtubule inhibitor Binds to tubulin and promotes its
assembly into microtubules while simultaneously inhibiting disassembly
Poor affinity for multidrug resistance proteins
20
Administration 20mg/m2 IV every 3 weeks + prednisone 10mg/day
Available Doses 60mg/1.5mL single dose vial
Infusion Time 1 hour
Pharmacokinetics Primarily CYP3A4 metabolism
Storage Stable for 8 hours at RT or 24 hours in refrigerator
Dosage Adjustments No adjustments
Monitoring Infusion reaction (premedicate)
Black Box Warnings Bone marrow suppression, hypersensitivity reactions
De Bono JS, et al. Lancet. 2010; 376:1147-1154.Jevtana [package insert]. Bridgewater, NJ: Sanofi-aventis; 2010.
De Bono JS, et al. Lancet. 2010; 376:1147-1154.Sartor AO, et al. ASCO. 2010:9(abstract)
Patients• 755 patients
with metastatic CRPC
• Progressed during and after docetaxel treatment
Randomized 1:1
Cabazitaxel25mg/m2
every 3 weeks + prednisone
N=378Primary Endpoints:• Overall
Survival
Secondary Endpoints:
• Progression-free survival, response rate, and safety
• QOL• Time to PSA
ProgressionMitoxanrone
12mg/m2 every 3 weeks +
prednisone N=377
21
Cabazitaxel Mitoxantrone
Median overall survival (months) 15.1 12.7
Tumor response rate (%) 14.4 4.4
PSA response rate (%) 39.2 17.8
Pain response rate (%) 9.2 7.7
Time to PSA progression (months) 6.4 3.1
De Bono JS, et al. Lancet. 2010; 376:1147-1154.
De Bono JS, et al. Lancet. 2010; 376:1147-1154.
Cabazitaxel (n=378) Mitoxantrone (n=377)
Adverse Reaction All Grades Grade 3-5 All Grades Grade 3-5
Neutropenia 347 (94%) 303 (88%) 325 (88%) 215 (58%)
Leukopenia 355 (96%) 253 (68%) 343 (92%) 157 (42%)
Anemia 361(97%) 39 (11%) 302 (81%) 18 (5%)
Thrombocytopenia 176 (47%) 15 (4%) 160 (43%) 6 (2%)
Diarrhea 173 (47%) 23 (6%) 39 (11%) 1 (<1%)
Fatigue 136 (37%) 18 (5%) 102 (27%) 11 (3%)
Asthenia 76 (20%) 17 (5%) 46 (12%) 9 (2%)
Nausea 127 (34%) 7 (2%) 85 (23%) 1 (<1%)
Vomiting 84 (23%) 7 (2%) 38 (10%) 0
Constipation 76 (20%) 4 (1%) 57 (15%) 2 (1%)
22
Second line treatment after docetaxel treatment for metastatic CRPC
First treatment to prolong survival in patients
May be considered for: Failed docetaxel therapy
De Bono JS, et al. Lancet. 2010; 376:1147-1154.
http://www.medscape.com/viewarticle/722776_4
23
Administration CRPC: 1000mg PO once daily + prednisone 5mg PO BIDCastration-sensitive prostate cancer: 1000mg PO once daily + prednisone 5mg PO once daily
Available Doses 250mg tablet and 500mg tablet
Dosage Adjustments Liver impairment
Drug Interactions Inhibits CYP2D6
Monitoring LFTs
Black Box Warnings None
De Bono, et al. N Engl J Med. 2011:364(21):1995-2005
De Bono, et al. N Engl J Med. 2011:364(21):1995-2005
Patients• 1195 patients
with metastatic CRPC
• Failed 1 or 2 chemotherapies, one containing docetaxel
Randomized 2:1
Abiraterone1000mg oral
daily + prednisone
5mg BID
N=797
Primary Endpoints:• Overall
Survival
Secondary Endpoints:
• Progression-free survival
• PSA response• QOL• Time to PSA
Progression
PlaceboN=398
24
De Bono, et al. N Engl J Med. 2011:364(21):1995-2005
Abiraterone Placebo
Overall survival (months) 14.8 10.9
Time to progression (months) 5.6 3.6
PSA response 38% 10.1%
De Bono, et al. N Engl J Med. 2011:364(21):1995-2005
Abiraterone (n = 797) Placebo (n = 398)
Adverse Reaction All Grades Grade 3-5 All Grades Grade 3-5
Fatigue 346 (44%) 66 (8%) 169 (43%) 39 (10%)
Fluid Retention and Edema
241 (31%) 18 (3%) 88 (23%) 4 (1%)
Back Pain 233 (30%) 47 (6%) 129 (33%) 38 (10%)
Nausea 233 (30%) 13 (2%) 124 (32%) 10 (3%)
Arthralgia 215 (27%) 33 (4%) 89 (23%) 16 (4%)
Constipation 206 (26%) 8 (1%) 120 (31%) 4 (1%)
25
Ryan CJ, et al. N Engl J Med. 2012:368(2):138-148.
Patients• 1088 patients
with progressive, metastatic CRPC
• Chemotherapy naive
Randomized 1:1
Abiraterone1000mg oral
daily + prednisone
5mg BID
N=544
Primary Endpoints:• Overall
Survival• Progression-
free survival
Secondary Endpoints:
• Time to chemotherapy initiation
• PSA response• Cancer pain
PlaceboN=544
De Bono, et al. N Engl J Med. 2011:364(21):1995-2005.Kluetz PG, et al. Clin Cancer Res. 2013:19:6650-6656.
Abiraterone Placebo
Overall survival (months) Not reached 27.2
Progression free survival (months) Not reached 8.3
Time to chemotherapy initiation (months) 25.2 16.8
Time to PSA progression (months) 11.1 5.6
Abiraterone Placebo
Overall survival (months) 35.3 30.1
Progression free survival (months) Not reached 8
26
Fizazi K, et al. N Engl J Med. 2017:377:352-360.
Patients• 1199 patients with
progressive, metastatic castration-sensitive prostate cancer
• Chemotherapy naive
Randomized 1:1
Abiraterone1000mg oral
daily + prednisone 5mg
daily
N=597
Primary Endpoints:• Overall Survival• Progression-free
survival
PlaceboN=602
Abiraterone Placebo
Overall survival (months) Not reached 34.7
Progression free survival (months) 33 14.8
Time to PSA progression (months) 33.2 7.4
Time to pain progression (months) Not reached 16.6
Median time to next symptomatic skeletal-related event (months)
Not reached Not reached
Median time to chemotherapy (months) Not reached 38.9
Median time to subsequent prostate cancer therapy (months)
Not reached 21.6
Fizazi K, et al. N Engl J Med. 2017:377:352-360.
27
First line therapy Chemotherapy naïve Metastasized CRPC and castration-sensitive prostate cancer
Second line therapy Metastasized CRPC First-line hormonal therapy has failed
May be considered for: Symptomatic or asymptomatic Visceral disease Therapy naïve or failed docetaxel
De Bono, et al. N Engl J Med. 364(21):1995-2005.Kluetz PG, et al. Clin Cancer Res. 2013:19:6650-6656.
Administration 500mg PO once daily + methylprednisolone 4mg PO BID
Available Doses 125mg tablet
Dosage Adjustments Liver impairment
Drug Interactions Inhibits CYP2D6
Monitoring LFTs
Black Box Warnings None
Yonsa [abiraterone acetate]. Cranbury: Sun Pharmaceutical Industries, Inc., NJ: 2018.
28
Blocks androgen receptor from moving into the nucleus and activating growth genes
Scher HI, et al. N Engl J Med. 2012:367(13):1187-1197.
Scher HI, et al. N Engl J Med. 2012:367(13):1187-1197.
Administration 160mg PO once daily
Available Doses 40mg capsule
Dosage Adjustments None
Drug Interactions CYP2C8 and CYP3A4
Monitoring LFTs
Black Box Warnings None
29
Scher HI, et al. N Engl J Med. 2012:367(13):1187-1197.
Patients• 1199 patients
with metastatic CRPC
• Failed docetaxeltreatment
Randomized 2:1
Enzaluatmide160mg oral
daily
N=800 Primary Endpoints:• Overall
Survival
Secondary Endpoints:
• PSA level response
• QOL• Time to PSA
Progression
PlaceboN=399
Enzalutamide Placebo
Overall survival (months) 18.4 13.6
Time to radiographic progression (months) 8.3 2.9
PSA 90% reduction from baseline (%) 25 1
Scher HI, et al. N Engl J Med. 2012:367(13):1187-1197.
30
Scher HI, et al. N Engl J Med. 2012:367(13):1187-1197.
Enzalutamide (n = 800) Placebo (n = 399)
Adverse Reaction All Grades Grade 3-5 All Grades Grade 3-5
Fatigue 269 (34%) 50 (6%) 116 (29%) 29 (7%)
Diarrhea 171 (21%) 9 (1%) 70 (18%) 1 (<1%)
Hot Flashes 162 (20%) 0 41 (10%) 0
Musculoskeletal Pain
109 (14%) 8 (1%) 40 (10%) 1 (<1%)
Headache 93 (12%) 6 (<1%) 22 (6%) 0
Cardiac Disorder 49 (6%) 7 (1%) 30 (8%) 8 (2%)
Patients• 1717 patients
progression on androgen deprivation with metastatic CRPC
• Chemotherapy naïve
Randomized 1:1
Enzaluatmide160mg oral
daily
N=872Primary Endpoints:• Overall Survival• Progression free
survival
PlaceboN=845
Beer TM, et al. Eur Urol. 2017:71:151-154.
31
Enzalutamide Placebo
Overall survival (months) 35.3 31.3
Time to radiographic progression (months) Not reached 3.7
Median time to chemotherapy initiation (months)
28.0 10.8
PSA 90% reduction from baseline (%) 41 1
Beer TM, et al. Eur Urol. 2017:71:151-154.
Patients• 1401 patients with
non-metastatic CRPC
• Chemotherapy naïve
Randomized 2:1
Enzaluatmide160mg oral daily
N=933 Primary Endpoints:• Metastasis-free
survival
PlaceboN=468
Hussain M, et al. N Eng J Med. 2018:378:2465-2474.
32
Enzalutamide Placebo
Metastasis-free survival (months) 36.6 14.7
First use of new prostate cancer therapy (months)
39.6 17.7
PSA progression 37.2% 3.9%
Overall survival Not reached Not reached
Death on study 32 (3.4%) 4 (0.9%)
Hussain M, et al. N Eng J Med. 2018:378:2465-2474.
First line therapy Non-metastasized and metastasized CRPC
Second line therapy Metastasized CRPC First-line hormone therapy has failed
May be considered for: Symptomatic or asymptomatic Visceral disease Therapy naïve or failed docetaxel
Does not have to be administered with prednisone Administered with gonadotropin-releasing
hormone if no bilateral orchiectomyScher HI, et al. N Engl J Med. 2012:367(13):1187-1197.
33
Binds directly to the ligand-binding domain of the androgen receptor and by inhibiting androgen receptor nuclear translocation, DNA binding, and androgen receptor-mediated transcription
Smith MR, et al. N Engl J Med. 2018:378:1408-1418.
Smith MR, et al. N Engl J Med. 2018:378:1408-1418.
Administration 240mg PO once daily
Available Doses 60mg tablet
Dosage Adjustments None
Drug Interactions Inhibits CYP3A4, CYP2C19, CYP2C9, UGT, P-gp, BCRP, or OATP1B1
Monitoring None
Black Box Warnings None
34
Patients• 1207 patients
with non-metastatic CRPC
Randomized 2:1
Apalutamide240mg oral
daily
N=860 Primary Endpoints:• Metastatic-
free Survival
Secondary Endpoints:
• Time to symptomatic Progression
PlaceboN=401
Smith MR, et al. N Engl J Med. 2018:378:1408-1418.
Smith MR, et al. N Engl J Med. 2018:378:1408-1418.
Apalutamide Placebo
Metastasis-free survival (months) 40.35 16.2
Median progression-free survival (months) 40.5 14.7
Median overall survival (months) Not reached 39
Median time to PSA progression (months) No reached 3.7
35
Smith MR, et al. N Engl J Med. 2018:378:1408-1418.
Apalutamide (n = 803) Placebo (n = 398)
Adverse Reaction All Grades Grade 3-5 All Grades Grade 3-5
Fatigue 244 (30%) 7 (1%) 84 (29%) 1 (<1%)
Hypertension 199 (25%) 115 (14%) 79 (20%) 47 (12%)
Rash 191 (24%) 42 (5%) 22 (5%) 1 (<1%)
Diarrhea 163 (20%) 8 (1%) 60 (15%) 2 (<1%)
Nausea 145 (18%) 0 63 (16%) 0
Weight Loss 129 (16%) 9 (1%) 25 (6%) 1 (<1%)
Arthralgia 128 (16%) 0 30 (8%) 0
Falls 125 (16%) 14 (2%) 36 (9%) 3 (<1%)
First line therapy Non-metastasized CRPC
May be considered for: Symptomatic or asymptomatic Therapy naïve
Administered with gonadotropin-releasing hormone if no bilateral orchiectomy
Smith MR, et al. N Engl J Med. 2018:378:1408-1418.
36
Osteoporosis prevention and treatment Calcium 1200mg/qd and vitamin D3 800-1000 IU/qd Bisphosphonates or denosumab
Long-term effects of prolonged ADT Fatigue Diabetes Weight gain
Bone metastasis Zoledronic acid, denosumab, radiation
▪ Monitor SrCr, osteonecrosis of the jaw, and hypocalcemia
The key to successful prostate cancer treatment is early detection
Clinical staging is important in determining the appropriate treatment
There are now treatment options for men with CRPC
Treatment always should be individualized
37
Megan May, Pharm.D., BCOPOncology Clinical Pharmacy SpecialistBaptist Health Lexington
top related