[ppt]powerpoint presentation - amazon s3 · web viewthompson im et al. n engl j med....
TRANSCRIPT
US Preventive Services Task Force (USPSTF) Screening Recommendations
• Per the 2012 USPSTF, no healthy man should undergo PSA screening unless symptoms of prostate cancer present
• Full implications have yet to be realized
Moyer VA, Ann Intern Med. 2012;157:120-34.
Task Force:– General physicians– Nurses– Health psychologists– Epidemiologists– Statisticians
Topic assigned by HHS Agency
for Healthcare Research &
Quality
Grade the quality of evidence-
based research
Defined prostate screening as
grade D recommendation
against the service. They had moderate or high certainty that the service has no net benefit or that
the harms outweigh the benefits.
Task Force set up by
congressional mandate in
1984
HHS=US Health & Human Services Department; PSA=prostate-specific antigen.
National Comprehensive Cancer Network (NCCN) Screening
Guidelines• NCCN panelists note the variability in prostate tumor behavior
– Key point is discussion between patient and provider about the risks and benefits of early detection of and treatments for prostate cancer
– Goal is to evaluate aggressiveness of the cancer• Once a patient age 40 starts having risk and benefit discussion about baseline
digital rectal exam (DRE) and absolute PSA values– May annually follow up with DRE and repeat PSA in patients with elevated
PSA (≥1.0 ng/mL), African Americans, men taking 5-alpha-reductase inhibitors
– Testing and biopsy decisions should be individualized for men > age 75 years
• Further timing of follow-ups and DRE and PSA testing dependent on age, and life expectancy– Trying to determine need for TRUS-guided biopsy, and may also use PSA
density, percent-free PSA, and PSA velocity to determine need for biopsy or if cancer is present
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer Early Detection, V2.2012. Accessed Sep 9, 2013.
PSA=prostate-specific antigen; DRE=digital rectal examination; TRUS=transrectal ultrasound.
American Cancer Society (ACS) Screening Guidelines
• ACS supports informed discussion between healthcare provider and asymptomatic men about screening for prostate cancer– Average risk: annually beginning age 50 years with 10+ year life
expectancy– Age 45 if high risk: High risk includes African-American men or
those with first-degree relative with prostate cancer <65 years of age
– Age 40 if very high risk: Very high risk includes multiple family members with prostate cancer at early age
– Include information about uncertainties, risks, and potential benefits• If testing performed, PSA with or without DRE• 2009 guidelines reaffirmed in 2013
Wolf AM, et al. CA Cancer J Clin. 2010;118:244-50.
American Urological Association (AUA) Screening Guidelines
• Recommendations based on age and risk– Average risk:
• < Age 40, not recommended• Age 40-54: do not recommend routine screening• Age 55-69: informed shared decision making about screening
risk and potential benefits• Age 70+ or patients with <10-15 years life expectancy: do not
recommend routine screening– Alternatively, can individualize based on baseline PSA
– High risk: <55 with positive family history or African-American race; decisions should be individualized
• If decision to screen, frequency should be 2+ years instead of annual – Panel believes this will reduce overdiagnoses and false-positives
while maintaining the majority of the benefits
Carter HB et al. J Urol. 2013;190:419-26
PSA-Based Prostate Screening
Potential Benefits• Earlier diagnosis:
– Allows finding cancer at earlier stage, before it is symptomatic, while it is likely localized
– 70% decrease in metastatic disease at diagnosis1
• Relative survival has increased to close to 100% since PSA screening became highly utilized1
– From 1975-1979, 10-year survival was 55.7%
– In 2000, 10-year survival was 98.4%
– US death rates have decreased about 4% per year
Risks and Limitations• Potential for overdiagnosis and
overtreatment in patients with clinically insignificant cancer– Decrease in quality of life,
complications, and cost• Various physiological and pathological
factors can cause a rise in PSA, often temporal
• If PSA detectable, no matter how low, prostate cancer still a possibility2
• Can take time for effect of population-based PSA screening to become significant3
• Though increase in survival of prostate cancer patients, not able to directly link it to PSA-based screening
1. Howlader N et al. SEER Cancer Statistics Review, 1975-2010, National Cancer Institute. http://seer.cancer.gov/csr/1975_2010/. Accessed Sept 2, 2013.
2. Thompson IM et al. N Engl J Med. 2004;350:2239-46. 3. Loeb S et al. J Clin Oncol. 2011;29:464-7.
Implications for Patient Care
• PSA-based screening not appropriate for overall population• Prostate cancer screening makes sense in certain populations
after informed discussion between patient and provider– Patients at high risk for the disease– Patients at high risk for death or morbidity from the disease– Patients in good health with life expectancy > 10-15 years
• Can be difficult deciding treatment versus observation for an individual patient
• Advise patients to seek a second opinion, especially with clinician experienced with both active surveillance and active treatment
Watchful Waiting vs Active Surveillance / Active Monitoring
Watchful WaitingActive
Surveillance / Active Monitoring
Primary aim Avoid treatment Individualize management
Patient / tumor characteristicsLimited life
expectancy/ advanced disease
Fit for radical treatment/
localized disease
Treatment timing Delayed Early
Treatment intent Palliative Curative
National Comprehensive Cancer Network (NCCN) Guidelines on Active Surveillance
Recurrence Risk Expected Survival Initial Therapy
Very low risk
< 20 years Active surveillance preferred
≥ 20 years1. Active surveillance
2. Radiotherapy3. Radical prostatectomy
Low risk ≥ 10 years1. Active surveillance
2. Radiotherapy3. Radical prostatectomy
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Prostate Cancer, V4.2013. Accessed Sep 1, 2013.
Summary of Active Surveillance Studies
Author N Median Follow-up
(mo)
pT3 in RP Patients
OS CSS
van As - Eur Urol. 326 22 8/18 44% 98 100
Carter - J Urol. 407 41 10/49 20% 98 100
PRIAS 533-1000 48 4/24 17% 90 99
Soloway 99 45 0/2 100 100
Roemeling 278 41 89 100
Khatami 270 63 Not stated 100
Klotz - J Clin Oncol.
452 73 14/24 58% 82 97 @ 10 yr
Total 2130-3000 43 90 99.7
CSS=cancer-specific survival; mo=months; OS=overall survival; p=pathologic; RP=radical prostatectomy.
Active Surveillance: Current Approach
• Offered to all men with Gleason 6, PSA ≤10 (accepted by most)• PSA kinetics a guide only• Confirmatory biopsy within 1 year, targeting
anterior/anterolateral horn• Repeat biopsy every 3-5 years (age, risk tolerance, PSA) to age
80 years• MP-MRI for PSA doubling time < 3 years or volume increase or
3+ minor element 4• Treat if significant Gleason 4 or unequivocal lesion > 1 cm on
MRI
Abiraterone Phase III Trials: COU-AA-301 and COU-AA-302
301 eligibility criteria:• Progressive mCRPC pts
who failed a docetaxel regimen ± another chemotherapy
302 eligibility criteria:• Progressive chemo-naïve
mCRPC, asymptomatic or mildly symptomatic
Abiraterone 1000mg qd+ prednisone bidRANDOMIZE
(N=1195)2:1
Placebo qd+ prednisone bid
Co-primary endpoints: OS + rPFS by central review
1. de Bono et al. N Engl J Med. 2011;364:1995-2005. 2. Ryan CJ, et al. N Engl J Med. 2013;368:138-48.
1:1(N=1088)
Primary endpoint: OS
Median OS Adverse Events
Abiraterone Placebo Abiraterone
COU-AA-301114.8 mo 10.9 mo Fluid retention and
edema, hypokalemia, cardiac disorders(P < 0.0001)
COU-AA-3022Not reached 27.2 mo Mineralocorticoid-
related + abnormalities on liver-function testing(P = 0.01)
Enzalutamide Phase III AFFIRM Trial
• Median OS: 18.4 mo enzalutamide, 13.6 mo placebo (P < 0.0001)• Adverse events: Enzalutamide group reported 45% of patients with any
≥ grade 3 adverse event vs 53% with placebo– 3% of enzalutamide group and 4% of placebo group had an adverse
event that led to death– Highest reported ≥ grade 3 adverse event was fatigue, with 6% of the
enzalutamide group and 7% of placebo reporting
Eligibility criteria:• CRPC pts who progressed
during or after treatment with a docetaxel-based regimen
Enzalutamide 160 mg qdRANDOMIZE
(N=1199)2:1
Placebo qdPrimary endpoint: OS
Scher HI et al. N Engl J Med. 2012;367:1187-97.mOS=median overall survival.
Second-Line Hormonal Therapy: Remaining Issues
• Optimal timing• Role of combination therapy• When to stop androgen biosynthesis inhibitors
– Major issue in the pre-chemotherapy setting• Optimal dose of steroids for androgen biosynthesis
inhibitors • Issues of divergent practice urology vs oncology
Endocrine Agents in Development
• Lyase inhibitors– Orteronel (TAK 700)– TOK-001 (galeterone)– CFG920– VT-464– EN3356
• Antiandrogens– ODM-201– ARN-509– AZD-3514– EZN-4176– TOK-001 (galeterone)
Docetaxel Hormone-Refractory Prostate Cancer
• Docetaxel + prednisone remains the standard of care for first-line chemotherapy for metastatic disease
• Investigating markers for drug resistance
N Randomized Arms Docetaxel Dosage Outcome (mOS in mo)
TAX 3271,2 1006
1. Mitoxantrone + prednisone
2. Weekly docetaxel + prednisone
3. Docetaxel q3w + prednisone
Arm 2: 30 mg/m2/wk 5 on; 1
off * 6 cyclesArm 3: 75 mg/m2
q3wk up to 10 cycles
• Weekly docetaxel had 1.5 mo benefit*
HR Arm 1,2: 0.94, P = 0.14• Docetaxel q3wk had 3
mo benefit*HR Arm 1,3: 0.88, P
=0.005
SWOG 99163 770
1. Mitoxantrone + prednisone
2. Docetaxel + Estramustine +
Dexamethasone
60 mg/m2 d2mOS: Arm 2 had 2 month median survival benefit
HR: 0.80; P = 0.01
1. Tannock et al. N Engl J Med. 2004;351:1502-12. 2. Berthold DR, et al. ASCO Prostate Cancer Symposium 2007; abstract 147. 3. Petrylak et al. New Engl J Med. 2004;351:1513-20.
*Compared to mitoxantrone arm. d2=day 2 of cycle; HR=hazard ratio; mos=months; mOS=median overall survival; pred=prednisone; q=every.
Phase III Trials of Docetaxel Combinations
• To date, no combination improves on docetaxel and prednisone
Docetaxel+Prednisone vs Docetaxel Combined With: Status Results
Bevacizumab Completed Negative
VEGF-Trap (aflibercept) Completed Negative
Atrasentan Completed Negative
ZD4054 Completed Negative
Dasatinib Completed Negative
Lenalidomide Completed Negative
Custirsen (OGX-011) OngoingPending,
completion December 2013
Phase III TROPIC Registration Study of Cabazitaxel vs Mitoxantrone in
Docetaxel-Resistant Patients
• mOS: 12.7 mo mitoxantrone+prednisone, 15.1 mo cabazitaxel+prednisone (P<0.0001)
• Adverse events: Cabazitaxel group reported 8% patients with ≥ grade 3 febrile neutropenia vs 1% in mitoxantrone– Diarrhea was reported in 6.2% of cabazitaxel group and 0.3% of
mitoxantrone group– Leukopenia also higher in cabazitaxel group (68% to 42%)
Eligibility criteria:• mCRPC pts who
progressed during or after treatment with a docetaxel-based regimen
Stratification:• ECOG PS (0, 1 vs 2)• Measurable vs non-
measurable disease
Cabazitaxel q3w + prednisone/prednisolone qd * 10 cyclesR
ANDOMIZE
(N=755)
Mitoxantrone q3w + prednisone/prednisolone qd * 10 cycles
Primary endpoint: OSSecondary endpoints: PFS, response rate, safety
de Bono et al. Lancet. 2010;376:1147-54.
Rationale for Immunologic Approaches in Prostate Cancer
1. Well-characterized cell surface molecules: PSA, PSMA, PAP, STEAP, PSCA, Globo H, GM2, MUC-1,2, Tn, TF, Lewisy
2. Biomarkers [PSA, CTCs] to study disease progression/response
3. Widely applicable to all disease states: – Biochemical relapse thru castration-resistant disease
4. Likely potentiated via combinatorial approaches: radiotherapy, chemotherapy, biologic agents (GM-CSF, IL-2) or checkpoint inhibitors (anti-CTLA-4, anti-PD-1), monoclonal antibody-chemo conjugates
Immunotherapies to Date…
Successes (limited)• Sipuleucel-T• Ipilimumab• PROSTVAC• Anti-PD-1
Failures (many)• G-Vax• Protein• Peptide• DNA
Brief Summary of Immunologic Trials in Prostate Cancer
• Sipuleucel-T autologous immunotherapy: Median overall survival benefit 4.1 mo in phase III IMPACT trial (P = 0.03)1
• PROSTVAC-VF vaccine: Primary endpoint of PFS in phase II trial similar with control, but at 3 years median overall survival benefit 8.5 mo (P = 0.006)2
• Ipilimumab antibody to CTLA-4: 10 mg/kg with or without radiotherapy had benefit for patients with tumor-evaluable disease in phase II trial,3 – Ipilimumab is being further tested in 2 phase III trials:
one in chemotherapy-naïve, the other in docetaxel-resistant cases
1. Kantoff PW et al. N Engl J Med. 2010;363:411-22.2. Kantoff PW et al. J Clin Oncol. 2010;28:1099-105. 3. Slovin SF et al. Ann Oncol. 2013;24:1813-21.
Conclusions on Immunologic Approaches in Prostate Cancer
• Not every immunotherapy fits a specific disease and vice versa
• Appropriateness of immune therapy for all clinical states of disease but clinical judgment prevails (ie, potential delay in impact of immune therapy)
• Combinatorial approaches: checkpoint inhibitors alone/together/chemo/RT/vaccines/cytokines
• Monoclonal antibody-chemo conjugates
Skeletal-Related Events in Cancer
• The skeleton is the most common site of metastasis• SRE: fracture, spinal cord compression, radiation or
surgery to bone, and hypercalcemia
Malignancy Site Bone Lesions SREsBreast 65%-75% 68%Prostate 90% 49%Lung 30%-40% 48%Multiple Myeloma 95%-100% 51%
Coleman. Cancer. 1997;80:1588-94. Bubendorf, et al. Hum Pathol. 2000;31:578-83. Saad, et al. Cancer. 2007;110:1860. Coleman. Oncologist. 2004;9:14-27.
SRE=skeletal-related event.
Phase III Trial of Denosumab vs Zoledronic Acid in Castration-Resistant
Prostate Cancer
• Supplemental calcium and vitamin D were strongly recommended
• Primary endpoint: (noninferiority) time to first on-study SRE • Secondary endpoint: superiority
Eligibility criteria:• Hormone-refractory
(castration-resistant)• ≥1 bone metastasisStratification:• Previous SRE• PSA concentration• Chemotherapy for prostate
cancer within 6 wks
Zoledronic acid 4 mg IV + placebo sc q4wk R
ANDOMIZE
(N=1901)
Denosumab 120 mg sc + placebo IV q4wk
IV=intravenous; SC=subcutaneous.
Fizazi et al. Lancet. 2011;377:813-22.
Phase III Trial of Denosumab vs Zoledronic Acid Results
Endpoint Denosumab Zoledronic Acid
HR (95% CI)P Value
Median time to first on-study SRE 20.7 mo 17.1 mo HR=0.82 (0.71-0.95)
P =0.008*
Median TTP 8.4 mo 8.4 mo HR=1.06 (0.95-1.18)P =0.30
Median OS 19.4 mo 19.8 mo HR=1.03 (0.91-1.17)P =0.65
Adverse Event, n (%) P ValueCTCAE grade 3/4 678 (72) 628 (66) 0.01
Hypocalcemia 121 (13) 55 (6) <0.0001
Cumulative ONJ 22 (2) 12 (1) 0.09
*P=0.0002 non-inferiority.CI=confidence interval; CTCAE=common terminology criteria for adverse events;
gr=grade; NR=not reported; TTP=time to progression. Fizazi et al. Lancet. 2011;377:813-22.
FDA-Approved Bone-Targeting Radionuclides for the Treatment of Bone
MetastasesFDA Approval Bone Agent Indication
March 20131 Radium-223
Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease
March 19972 Samarium-153 lexidronam
Relief of pain in patients with confirmed osteoblastic metastatic
bone lesions that enhance on radionuclide bone scan
June 19933 Strontium-89 Relief of bone pain in patients with painful skeletal metastases
1. Xofigo [package insert]. Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2013. 2. Quadramet [package insert]. Princeton, NJ: EUSA Pharma (USA), Inc.; 2009. 3. Metastron [package insert]. Arlington Heights, IL: Medi-
Physics, Inc.; 1998.
Bone-Targeting Radionuclides for Patients with Prostate Cancer Bone
MetastasesTrial Bone Agent N Results (Improvement Over or vs
Placebo)
Sartor, 2004 phase III
Samarium-153-lexidronam 101 VAS: 2-4 wk (P≤0.05)
PDS: 1-4 wk (P≤0.05)Analgesic use: 3-4 wk (P< 0.03)Placebo 51
Porter, 1993 phase III
Stronium-89 + EBR 126
New painful sites: 0.6 vs 1.2 (P< 0.0002)Analgesic free at 3 mo: 17% vs 2% (P<0.05)Time to further RT: 35 vs 20 wk (P=0.006)Placebo + EBR
Parker, 2013phase III
Radium-223 614 Median OS: 65 vs 49 wk (P <0.001)Median time to first symptomatic skeletal event: 68 vs 43 wk (P <0.001)Placebo 307
ALP=alkaline phosphatase; EBR=external beam irradiation; PDS=pain descriptor scale (nonlinear); RT=radiotherapy; VAS=100-mm pain intensity visual analog scale (linear).
Sartor et al. Urology. 2004;63:940-5. Nilsson et al. Lancet Oncol. 2007;8:587-94. Porter et al. Int J Radiat Oncol Biol Phys. 1993;25:805-13.
Cabozantinib in Bone Metastatic Prostate Cancer
• Phase II Trial1– Cabozantinib administered 100 mg daily– 67% of patients (total N=171) showed bone scan response after
retrospective review– Reduction in bone markers– Other benefits:
• Pain improvement and narcotics reduction• PFS benefit seen regardless of docetaxel pretreatment or naïve • PSA changes discordant with other measures of antitumor activity
• 2nd trial to attempt lower starting doses to limit adverse events2
– Primary outcome was week 6 bone scan response– For N=24 at 40 mg, 1 complete response, 15 partial responses,
8 stable disease with tolerable adverse event profile• Phase IIIs ongoing
1. Smith DC et al. J Clin Oncol. 2013;31:412-19. 2. Lee RJ et al. Clin Cancer Res. 2013;19:3088-94.
Conclusions on Novel Therapies and Bone-Targeted Therapies
• Alpha-emitting isotope therapy improves survival in men with CRPC
• Minimal toxicity• Combination studies with
hormonal/chemotherapeutic agents are underway• New agents are targeting bone and have promising
activity
Can We Combine Novel Agents in the Management of
Advanced Prostate Cancer?Robert Dreicer, MD, MS, FACP, FASCO
Combination Therapy in Metastatic Castration-Resistant Prostate Cancer:
Current Status• Testosterone suppression
– + second-line hormonal therapy– + sipuleucel-T– + docetaxel, + bone-targeted agents– + radiotherapy
Brief Summary of Abiraterone + Enzalutamide Trials in Prostate
Cancer• Phase II MDV3100 in bone metastatic CRPC
(NCT01650194)– N=60, prior chemotherapy allowed
• Proposed Intergroup 3-arm phase III metastatic CRPC– Enzalutamide + abiraterone + prednisone– Enzalutamide monotherapy– Abiraterone + prednisone
CRPC=castration-resistant prostate cancer; Ph=phase.
Combination and/or Sequential Therapy in CRPC: Challenges
• Current reimbursement paradigm is slowly but inexorably coming to an end.
• Compendium listing of drugs will be nice, but will increasingly miss the point.
• In a world of Accountable Care Organizations, medical homes, and contracts for populations, we need to think about VALUE in addition to science/clinical results.
Radium-223 Combination Therapy
• Excellent toxicity profile
• Unique mechanism of action
• Combination studies with androgen receptor-targeted agents
– Issues of other bone-targeted therapy when combined with two potent agents that decrease SREs/impact survival
• Combination with immunomodulatory agents
Near-Term Questions for Combination Therapy
• Can more-potent androgen receptor-targeted therapy cure patients with minimal disease?
– The adjuvant breast paradigm
– Lyase inhibitor + next-generation androgen receptor antagonist
• Locally-advanced prostate cancer status post combined modality therapy
• Cost effective/value-based care questions
Potential DNA Biomarkers• APC = adenomatosis polyposis coli
– Inactivated in various malignancies including prostate cancer by genetic and epigenetic mechanisms
• GSTP1 = glutathione-S-transferase-P1/π– Believed to play a role in the protection of DNA from oxidative
damage• RASSF1A = Ras association domain family 1 isoform A
– Tumor suppressor• RARβ2 = retinoic acid receptor β2
– Tumor suppressor• MDR1 = multidrug resistance 1
– May play a role in anticancer drug resistance• CCND2 = cyclin D2
– Cell-cycle regulator
PSA Response to CRPC
• While a ≥50% decrease from baseline has been accepted as clinically relevant response,1 a ≥30% decrease has also been demonstrated as a surrogate threshold for predicting survival.2,3
• Record the percentage change from baseline (rise or fall) at 12 weeks, and separately, the maximal change (rise or fall) at any time using a waterfall plot.4
1. Scher HI, et al. J Clin Oncol. 2011;29:3695-704. 2. Petrylak DP, et al. JNCI. 2006;98:516-21. 3. Armstrong AJ, et al. J Clin Oncol. 2007;25:3965-70. 4. Scher HI, et al. J Clin Oncol. 2008;26:1148-59.
PSA Does Not Always Accurately Reflect Response to CRPC Therapy
• Newer therapies, such as sipuleucel-T will improve survival without decreasing PSA levels.
• For cytotoxic or hormonal therapies, early PSA responses, rises or declines, should not be used for clinical decision making.1
– Discordance between PSA change and clinical responses, such as pain response2 or progression/regression of bone metastases, have been reported.3
1. Scher HI, et al. J Clin Oncol. 2008;26:1148-59. 2. Berthold DR, et al. Clin Cancer Res. 2008;14:2763-7. 3. Ryan CJ, et al. Clin Cancer Res. 2011;17:4854-61.
Other Biomarkers With Correlation to Outcomes in Prostate Cancer
Biomarker Population Correlation
Testosterone (T)1,2
Retrospective newly diagnosed bone-only
metastatic treated with LHRH agonist
Correlation of serum T and intraprostatic DHT:• None seen at beginning• Could be observed after 6 mo
neoadjuvant ADT
Circulating tumor cells (CTCs)
CRPC patients receiving chemotherapy3
ORMetastatic CRPC pts on
abiraterone after failing on docetaxel4
• CTCs are useful for predicting treatment response/survival with cytotoxic and hormonal therapies
• However, ~50% of patients do not have detectable CTC levels by current detection methods
• More-ensitive CTC detection techniques needed
1. Perachino M, et al. BJUI. 2010;105:648-51. 2. Nishiyama T, et al. Cancer Res. 2004;10:7121-6. 3. de Bono JS, et al. Clin Cancer Res. 2008;14:6302-9.
ADT=androgen-deprivation therapy; DHT=dihydroxytestosterone; LHRH=luteinizing hormone-releasing hormone
Other Biomarkers With Correlation to Outcomes in Prostate Cancer (cont.)
Biomarker Population Correlation TMPRSS2-ERG fusion1-4
– Rearrangements present ~50% of newly diagnosed patients
– Creates androgen receptor-driven expression of ERG
TMPRSS2-ERG no rearragement, Edel (1 or
2+), and Esplit patient samples
• Exact rearrangement may indicate lethality of tumor2,3
• Association between ERG fusion and PSA decline seen in patients treated with abiraterone4
AR35
– In vitro studies suggest AR3 promotes androgen-independent growth
Patient samples from benign, hormone-naïve, and hormone-resistant
tumors
AR3 appears to be upregulated during prostate cancer progression during hormone therapy, and is associated with androgen-resistant growth
Interleukin (IL)-6Metastatic CRPC6 and
metastatic CRPC receiving first-line docetaxel7
• Higher baseline IL-6 associated with worse prognosis6,7
• Correlation with response to docetaxel7
1. Danila DC, et al. Eur Urol. 2011;60:897-904. 2. Mehra R, et al. Cancer Res. 2008;68:3584-90. 3. Attard G, et al. Oncogene. 2008;27:253-63. 4. Attard G, et al. Cancer Res. 2009;69:2912-8. 5. Guo Z, et al. Cancer Res.
2009;69:2305. 6. George DJ, et al. Clin Cancer Res. 2005;11:1815-20.