evolving use of chemotherapy for metastatic … · 2017. 9. 19. · 3 2017 nccn recommendations for...
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EVOLVING USE OF CHEMOTHERAPY FOR METASTATIC PROSTATE CANCER Daniel George, MD Professor of Medicine and Surgery Director of Genitourinary Oncology Program Duke Cancer Institute
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70 yo WM presents with acute urinary obstruction.
Foley catheter placed Bone scan – multiple mets TRUS/Bx: Gleason 4+5 SOB: DVT and PE Started on Enoxaparin,
Degarelix
Illustrative Case
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2017 NCCN Recommendations for M1 Castrate-Sensitive Prostate Cancer
Orchiectomy, or LHRH agonist +/- anti-androgen > 7 days, or LHRH agonist + anti-androgen, or LHRH antagonist, or ADT and docetaxel 75 mg/m2 with or without
prednisone for 6 cycles https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
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CHAARTED STUDY SCHEMA
ADT allowed up to 120 days prior No intermittent ADT Dex given with chemo but no prednisone
Sweeney CJ et al N Engl J Med. 2015 Aug 20;373(8):737
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CHAARTED: Baseline Characteristics
Sweeney CJ et al N Engl J Med. 2015 Aug 20;373(8):737
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Primary Endpoint: Overall Survival
Sweeney CJ et al N Engl J Med. 2015 Aug 20;373(8):737
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Secondary Endpoint: OS by extent of disease
High volume defined by 4 or more osseous mets, non-axial mets, or visceral mets
Sweeney CJ et al N Engl J Med. 2015 Aug 20;373(8):737
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Additional Secondary Endpoints
Sweeney CJ et al N Engl J Med. 2015 Aug 20;373(8):737
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Grade 3-5 adverse events with docetaxel
Sweeney CJ et al N Engl J Med. 2015 Aug 20;373(8):737
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Addition of docetaxel to long term ADT in M1 CSPC (STAMPEDE). STAMPEDE is a multi-arm, multi-stage, adaptive
platform design trial to compare evolving combination therapies to standard of care ADT
Broad population including locally advanced (N0M0) to M1 newly diagnosed CSPC patients
Compared 4 treatment regimens randomized 2:1:1:1 (ADT alone; ADT + ZA; ADT + Doc; ADT + ZA + Doc)
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
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STAMPEDE: Trial Profile
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
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STAMPEDE: Patient Characteristics
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
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Docetaxel Treatment Arms
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
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STAMPEDE Results: PFS and OS Zoledronic Acid alone arm vs SOC
HR 0.94 95% CI 0.74 – 1.11; p = 0.450
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
HR 0.92 95% CI 0.81 – 1.04; p = 0.198
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STAMPEDE Results: PFS and OS for Docetaxel arms vs SOC
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
HR 0.78; 95% CI 0.66 – 0.93; p = 0.006
HR 0.82; 95% CI 0.69 – 0.97; p = 0.022
HR 0.61; 95% CI 0.53 – 0.93; p < 0.001
HR 0.62; 95% CI 0.54 – 0.93; p < 0.001
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Subgroup Analysis for SOC vs SOC + Doc
James ND, et al. Lancet. 2016 Mar 19;387(10024):1163-77
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Future Questions
What is the role of novel anti-androgens/ androgen synthesis inhibitors in this context? • Anzamet, ARCHES, ARASENS
Does radium-223 add to chemotherapy in this setting? • Alliance/NRG Phase III
Is there a role for consolidative radiotherapy, surgery or both?
Is there a role for SBRT to oligometastatic disease?
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Summary
Docetaxel chemotherapy in combination with ADT in newly diagnosed M1 CSPC is a standard of care
Zoledronic acid did not improve OS alone or in combination with docetaxel
Benefit was seen broadly across M1 disease; however, in CHAARTED greater benefit was seen in extensive disease patients
mCSPC represents an important population for clinical trials!