ESMO SUMMIT LATIN AMERICA 2019 Prostate cancer Clinical cases discussion LUIS ANTONIO LARA MEJÍA MD Medical Oncology Fellow Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México CHAIR: MARIA TERESA BOURLON DE LOS RIOS MD MS
CLINICAL CASE 1
CASE PRESENTATION A 58-year-old male, lawyer, married, born and living in Mexico City. • Family History: o No relevant family history. • Past Medical History: o Tobacco use → 12 pack - years. Discontinued 2 years ago. o Hypertension (2015) → well - controlled, treated with enalapril 5 mg BID.
HISTORY OF PRESENT ILLNESS 06/2011 11/2011 Lower urinary tract symptoms Dysuria and suprapubic pain Physical exam Lab tests DRE: enlarged prostate gland. • • PSA: 15 ng/mL Lab tests Procedures PSA: 9 ng/mL • • TURP: benign prostatic hyperplasia. Transrectal biopsy Prostate biopsy: benign prostatic • hyperplasia
HISTORY OF PRESENT ILLNESS 05/2016 Cough, exertional dyspnea, unintentional weight loss Laboratory tests (15 kg in 5 months). Hb 10 Leu 3 Neu 66% Plt 222 • • Cr 0.9 BUN 14 TB 0.5 ALT 7 AST 22 ALP 209 • Physical exam TP 6 Alb 3.8 • • PSA: 909 ng/mL Bilateral pleural effusion. • • Left supraclavicular lymph node. Thoracentesis Chest CT scan Exudative pleural effusion. • No malignant cells in cytology • • Bilateral pleural effusion, right lung mass.
Left supraclavicular lymph node
Right lung mass Bilateral pleural effusion
Retroperitoneal LAD
Left iliac LAD
Post-TURP changes Sclerotic bone lesions
99TC-MDP BONE SCAN
RADIOLOGY Chest, abdomen and pelvis CT scan • Heterogeneous prostate (post - TUPR) Inferior vena cava compression • • Pelvic, retroperitoneal and left supraclavicular LAD Bilateral pleural effusion • Right lung mass • 99Tc-MDP bone scan Multiple axial and peripheral bone metastases •
PATHOLOGY Left supraclavicular LN excisional Lung mass percutaneous biopsy biopsy • Metastatic prostate adenocarcinoma (PSA+, prostatic ALP+) Undifferentiated metastatic acinar • adenocarcinoma.
QUESTION 1 What would be your approach in the treatment of this patient? At presentation • Multidisciplinary approach • Early chemotherapy or highly effective antiandrogen therapy at diagnosis
CHAARTED Patients with hormone-sensitive metastatic prostate cancer ADT + docetaxel 57.6 months N = 790 HR 0.61 (95% CI 0.47-0.80) p < 0.001 393 397 ADT ADT + Docetaxel 75mg/m2 3w ADT alone 44 months Subgroup analysis - High-volume vs low-volume disease N Engl J Med. 2015 Aug 20;373(8):737 - 46
CHAARTED High volumen disease ADT + docetaxel 49.2 months HR 0.60 (95% CI 0.45-0.81) p < 0.001 ADT alone 32.2 months N Engl J Med. 2015 Aug 20;373(8):737 - 46
CHAARTED + STAMPEDE + GETUG- AFU15 OS 4 years ; absolute benefit 9% (40 to 49%) 23% reduction in the risk of death Lancet Oncol . 2016 17(2):243 - 56
LATITUDE Patients with hormone-sensitive metastatic prostate cancer N = 1199 OS: 34.7 months vs NR Follow-up 30.4 months 602 597 ADT + ADT + placebo abiraterona + prednisone High-risk features - Gleason score ≥ 8 - Three or more bone lesions - Visceral disease N Engl J Med. 2017 Jul 27;377(4):352 - 360
ARCHES Patients with hormone-sensitive metastatic prostate cancer N = 1150 Follow up: 14.4 m PE: rPFS ENDPOINT ENZ + ADT PBO + ADT HR rPFS NR 19.4 m 0.39 576 p<0.0001 574 ADT + enzalutamide ADT + PSA 68.1% 17.6% Placebo 160mg/d undetectable ORR 83.1% 63.7% 67% distant metastases, 63% High-volume disease 66% GSC >8 18% prior docetaxel J Clin Oncol 37, 2019 (suppl 7S; abstr 687)
QUESTION 2 Do you have any preference in choosing abiraterone or enzalutamide vs docetaxel as first- line treatment for hormone- sensitive disease?
MANAGEMENT The patient started treatment with: - Leuprolide 22.5 mg SC every three months + bicalutamide 50 mg every day for four weeks. - Docetaxel 75 mg/m 2 every 21 days for 6 cycles.
PSA RESPONSE 1000 Leuprolide + 900 bicalutamide 800 700 600 500 Docetaxel Docetaxel 6 th cycle 400 1 st cycle 300 200 100 0 26-may-16 29-may-16 19-jun-16 02-jul-16 02-sep-16 23-sep-16 15-oct-16 05-nov-16 26-nov-16 11-feb-17 21-Apr-17 PSA level
Initial response ADT + docetaxel Pre Chemotherapy Post Chemotherapy
Initial response ADT + docetaxel Pre Chemotherapy Post Chemotherapy
INITIAL RESPONSE ADT + DOCETAXEL Pre Chemotherapy Post Chemotherapy
TREATMENT RESPONSE AND ADVERSE EVENTS PSA course Adequate response Radiographic partial response (RECIST 1.1) ECOG 1 Tolerable ADT-related side effects. Grade 1 fatigue, grade 1 nausea.
HISTORY OF PRESENT ILLNESS 06/2018 06/2018 Asymptomatic, ECOG 0 CRPC 8 Lab tests 6.86 7 PSA: 4.66 → 6.86 ng/mL • 6 4.66 • Serum testosterone : 0.14 ng/ dL 5 4 3 1.8 1.43 1.39 2 1 1.42 1.5 Imaging 0 Apr-17 May-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Jan-18 Feb-18 Mar-18 Apr-18 May-18 Jun-18 • CT scan: stable visceral disease, new bone lesions • Bone scan: new axial and appendicular bone lesions
QUESTION 2 What is the best treatment option for this patient?
DRUGS APPROVED FOR CRPC
OPTIONS IN CRPC SETTING PSA response Overall Drug HR >50% survival Docetaxel 45% 2.4m 0.76 Visceral disease, significant pain. Cabazitaxel 39% 2.4m 0.70 Previous chemotherapy, neutropenia Sipuleucel T <5% 4.1m 0.78 Low tumour burden, high cost. Abiraterone 38% 4.6m 0.74 (postQT) Few symptoms, prednisone use, hypertension, hypocalemia. Abiraterone (preQT) 62% 5.2m 0.79 Enzalutamide 54% 4.8m 0.63 (postQT) Visceral disease, no prednisone, seizures <1%. Enzalutamide 78% 2.2m 0.71 (preQT) Radium- 223 --- 2.8m 0.70 Only bone disease.
MANAGEMENT The patient continued ADT therapy with leuprolide and started with: - Enzalutamide 160 mg/daily. - Zoledronic acid 4 mg every 3 months.
PSA RESPONSE - CRPC PSA level 8 7 6 Enzalutamide started 5 4 Enzalutamide 3 PFS 6 months 2 1 0 PSA level
PATIENT FOLLOW UP Radiographic stable disease (RECIST 1.1) ECOG 1 Tolerable ADT-related side effects Grade 1 fatigue PFS 6 months Clinical benefit
CLINICAL CASE 2
CASE PRESENTATON A 77 -year-old Mexican male, married, born and living in Mexico City. • Family History: o No relevant family history • Past Medical History: o No past medical history
HISTORY OF PRESENT ILLNESS 08/2016 10/2016 Lower urinary tract symptoms Up -front metastatic & weight los (7kgs) disease Radiological images Physical exam • CT scan: abdominal retroperitoneal lymphadenopathy • DRE: enlarged prostate gland. • Bone scan: left iliac bone lesion Lab tests • PSA: 121 ng/mL Imaging studies Transrectal biopsy Acinar adenocarcinoma, Gleason • 5+5, with extraprostatic extension
Up front metastatic disease Enlarged prostate Pelvic adenopathies Anterior rectal invasion
99TC-MDP BONE SCAN
HISTORY OF PRESENT ILLNESS 10/2016 02/2017 1st line hormone -sensitive disease 6 cycles docetaxel 75mg 3W PSA response PSA 142 ng/ml • Leuprolide 7.5mg/month + • • 25 ng/ml bicalutmide Docetaxel for 6 cycles • PSA level 160 142 140 Biochemical 120 response 100 1st cycle Cycle 6 80 Docetaxel Docetaxel 60 Leuprolide + 47 40 33 30 25 Bicalutamide 20 21 19 0 12/08/2016 12/09/2016 12/10/2016 12/11/2016 12/12/2016 12/01/2017 PSA level
Partial response • Nodal disease After 6 cycles of Docetaxel
HISTORY OF PRESENT ILLNESS 02/2018 04/2018 CRPC Biochemical progression Docetaxel rechallenge (no access • PSA: 62 ng/mL to other therapies) • Testosterone 0.1 • CT scan: stable disease • Bone scan: stable disease Docetaxel 3 cycles: • PSA clinical response • Cycle 5 PSA level Docetaxel: 5th docetaxel cycle • Docetaxel docetaxel Lower back pain & fatigue 80 rechallenge 67 clinical & biochemical 62 60 Cycle 3 progression 40 PSA: 67 ng/mL 28 • 21 20 0 01/01/2018 01/02/2018 01/03/2018 01/04/2018 PSA level Testosterone
Progression of nodal disease Unilateral hydronephrosis
QUESTION 1 What is your experience with docetaxel rechallenge in castration resistance disease?
DOCETAXEL RECHALLENGE GETUF- AFU15 Retrospective analysis First or second line treatment for mCRPC N=245 (71%) N=42 134 ADT alone 111 ADT + docetaxel 45% Rechallenge after ADT + D in mCNPC 1. bPFS 2. Maximum decline of PSA 3. OS 14% 1st line ADT ADT + D Docetaxel 38% 20% No correlation between time to progression Bicalutamide 43% 17% after upfront ADT + D & PSA response on rechallenge ABI or ENZ 84.2% 53% Eur Urol. 2018 May;73(5):696 - 703
PFS Biochemical 1st or 2nd line 3.4 m 6 m 4.1 m
DOCETAXEL RECHALLENGE Local evidence (México) Docetaxel + ADT CRPC Retrospective analysis (2015-2017) 1 st line Docetaxel N = 8 rechallenge % change in PSA Disease free survival (%) levels after docetaxel PFSm 31.8 sem rechallenge (95%IC 16.6 - 42.4) 25% Weeks Median of cycles: 5.8 Gonzalez et al (2018) INCMNSZ
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