ESMO Supporter 2018

Displaying One Session

ICM - Room 13 Proffered Paper session
Date
19.10.2018
Time
14:00 - 15:30
Location
ICM - Room 13
Chairs
  • Eleni Efstathiou (Houston, US)
  • Silke Gillessen (Manchester, GB)
Proffered paper session - Genitourinary tumours, prostate Proffered Paper session

791O - Updated results of GETUG-12, a phase 3 trial of docetaxel-based chemotherapy in high-risk localized prostate cancer, with a 12-year follow-up.

Presentation Number
791O
Lecture Time
14:00 - 14:15
Speakers
  • Karim Fizazi (Villejuif, FR)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

GETUG-12 assessed docetaxel-estramustine in patients with high-risk localized prostate cancer: the primary endpoint of relapse-free survival (RFS) was met (adjusted HR: 0.71 [95% CI: 0.54-0.94], p = 0.017) (Lancet Oncol 2015; 16: 787-94). This analysis updates RFS and assesses clinical events for the first time.

Methods

Eligibility included non-pretreated high-risk localized prostate cancer, defined as ≥ 1 of the following: T3-T4, Gleason ≥8, PSA ≥20 ng/mL, pN + (stratification factors). All 413 patients had a staging pelvic lymph node dissection. Patients were randomized to goserelin for 3 years and 4 cycles of docetaxel 70 mg/m2 + estramustine 10 mg/kg/d days 1-5, every 3 weeks (ADT+DE arm) or goserelin alone (ADT arm). Local therapy (radiotherapy: 87%) was administered at 3 months. Outcomes were tested with a pre-specified order (1: RFS, 2: clinical RFS (cRFS), and 3: metastases-free survival (MFS)) by the fixed-sequence method for controlling the family-wise error rate when conducting tests for multiple endpoints. RFS events: biochemical failures, metastases, proven local relapses, use of salvage treatment, and deaths. cRFS events: metastases, proven local relapses, and deaths. MFS events: metastases and deaths.

Results

With a median follow-up of 12 years [95% CI 11.9–12.2], 233 patients (56%) have had an event. RFS was improved in the ADT+DE arm: 12-year RFS rate: 49.4% [42.5%; 56.3%] in the ADT+DE arm vs 36.3% [29.7%; 43.5%] in the ADT arm (adjusted HR: 0.71 [0.55; 0.93], p = 0.01). The median RFS was 11.6 [9.1; NR] and 8.1 [7.3; 9.6] years. cRFS was also significantly improved in the ADT+DE arm (adjusted HR: 0.75 [0.56 ; 1.00]; p = 0.0491); 12-year rates: 58.8% [51.7% ; 65.6%] vs 50.5% [43.4% ; 57.6%]; median cRFS: 13.9 (13.3-14.9) vs 12.5 (9.9-15.3) years. 12-year MFS rates were 62.2% [55.1%; 68.8%] and 55.8% [48.6%; 62.8%] (adjusted HR: 0.81 [0.60; 1.09]. 12-year PC-specific survival rates were 88.2% [82.5%; 92.2%] and 83.9% [77.4%; 88.8%] (adjusted HR: 0.70 [0.40; 1.22]). The 12-year cumulative rates of second cancers (16.4% vs 18.8%) were similar.

Conclusions

Four cycles of docetaxel-based chemotherapy reduces the risk of clinical relapse or death in men with high-risk localized prostate cancer.

Clinical trial identification

NCT00055731.

Legal entity responsible for the study

UNICANCER.

Funding

UNICANCER.

Disclosure

K. Fizazi: Advisory boards, honorarium: Sanofi. F. Joly: Advisory boards: Sanofi. G. Gravis: Travel expense: Sanofi, Janssen, Astellas. L. Mourey: Travel expense, honoraria: Sanofi. All other authors have declared no conflicts of interest.

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Proffered paper session - Genitourinary tumours, prostate Proffered Paper session

Invited Discussant 791O

Lecture Time
14:15 - 14:30
Speakers
  • Eleni Efstathiou (Houston, US)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30
Proffered paper session - Genitourinary tumours, prostate Proffered Paper session

LBA30 - ERA 223: A phase 3 trial of radium-223 (Ra-223) in combination with abiraterone acetate and prednisone/prednisolone for the treatment of asymptomatic or mildly symptomatic chemotherapy-naïve patients (pts) with bone-predominant metastatic castration-resistant prostate cancer (mCRPC)

Presentation Number
LBA30
Lecture Time
14:30 - 14:45
Speakers
  • Matthew R. Smith (Boston, US)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

Abiraterone acetate and prednisone/prednisolone (AAP) improves progression-free survival and overall survival (OS) in men with mCRPC. Ra-223 increases OS and decreases symptomatic skeletal events (SSEs) in men with mCRPC and bone metastases. We evaluated concurrent treatment with AAP and Ra-223.

Methods

This phase 3, double-blind, placebo (PBO)-controlled trial randomised asymptomatic/mildly symptomatic men with chemotherapy-naïve mCRPC and bone metastases in a 1:1 ratio of AAP + Ra-223 or AAP + PBO. Bone health agents (BHAs [bisphosphonates or denosumab]) were only allowed in pts receiving them at baseline. The primary endpoint was SSE-free survival (SSE-FS).

Results

806 pts were randomised (401 to AAP + Ra-223; 405 to AAP + PBO); 39% and 42% of pts were receiving BHAs at baseline in the AAP + Ra-223 and AAP + PBO arms, respectively. The trial was unblinded early after more fractures and deaths were observed in the AAP + Ra-223 arm. All pts had completed study-specified Ra-223/PBO treatment prior to unblinding. At the primary analysis, median SSE-FS was 22.3 mo (95% CI 20.4−24.8) with AAP + Ra-223 and 26.0 mo (95% CI 21.8−28.3) with AAP + PBO (HR 1.122, 95% CI 0.917−1.374; p=0.2636). Median OS was 30.7 mo (95% CI 25.8−not estimable) with AAP + Ra-223 and 33.3 mo (95% CI 30.2−41.1) with AAP + PBO (HR 1.195, 95% CI 0.950−1.505; p=0.1280). Other secondary/exploratory endpoints are shown in the Table. Fractures occurred in 29% and 11% of pts in the AAP + Ra-223 and AAP + PBO arms, respectively. In pts receiving BHAs, 15% and 7% experienced a fracture in the AAP + Ra-223 and AAP + PBO arms, respectively, vs 37% and 15% without BHAs.

AAP + Ra-223
N=401
AAP + PBO
N=405
HR (95% CI)
Additional secondary endpoints
rPFS (central review), median (95% CI), months 11.2 (9.1–11.8) 12.4 (10.8–14.5) 1.152 (0.960–1.383)
Time to cytotoxic chemotherapy, median (95% CI), months 29.5 (26.5–35.7) 28.5 (23.7–NE) 1.033 (0.816–1.308)
Time to opiate use for cancer pain, median (95% CI), months 19.0 (14.4–23.2) 22.6 (18.0–25.7) 1.126 (0.921–1.378)
Exploratory endpoints
Overall confirmed PSA response, n/N (%) 287/396 (72) 267/401 (67)
Time to PSA progression, median (95% CI), months 9.6 (8.2–10.8) 9.0 (7.9–10.1) 0.937 (0.792–1.108)
Overall confirmed ALP response, n/N (%) 218/398 (55) 104/402 (26)
Time to ALP progression, median (95% CI), months 7.4 (7.1–7.9) 6.8 (5.3–8.4) 1.083 (0.918–1.276)
Time to deterioration in health-related quality of life*,
median (95% CI), months
9.5 (6.9–12.0) 10.5 (8.3–13.0) 1.079 (0.865–1.345)
*As reported in the safety population (AAP + Ra-223 N=392, AAP + PBO N=394) using the NCCN-FACT FPSI-17 physical disease-related symptoms subscale score measured during the treatment period. ALP: alkaline phosphatase; NE: not estimable; PSA: prostate-specific antigen; rPFS: radiological progression-free survival.

Conclusions

Concurrent AAP + Ra-223 treatment did not improve SSE-FS or OS and led to a higher fracture rate. Based on these results, we do not recommend Ra-223 in combination with AAP.

Clinical trial identification

NCT02043678

Editorial Acknowledgement

Medical writing support was provided by Michael Sheldon, PhD, of Scion, London, UK, funded by Bayer

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Proffered paper session - Genitourinary tumours, prostate Proffered Paper session

Invited Discussant LBA30

Lecture Time
14:45 - 15:00
Speakers
  • Daniel Heinrich (Lørenskog, NO)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30
Proffered paper session - Genitourinary tumours, prostate Proffered Paper session

792O - A Randomized Phase 2 Study of Cabazitaxel (CAB) vs (ABI) Abiraterone or (ENZ) Enzalutamide in Poor Prognosis Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Presentation Number
792O
Lecture Time
15:00 - 15:15
Speakers
  • Kim N. Chi (Vancouver, CA)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30

Abstract

Background

The optimal treatment for poor prognosis mCRPC is undefined and includes either taxane chemotherapy or androgen receptor (AR) targeted therapy, emphasizing the need for predictive biomarkers.

Methods

Patients (pts) with poor prognosis (liver metastases, early CRPC (<12 months from ADT start), and/or >3 of 6 poor prognostic criteria (Chi et al, Annals of Oncol, 2016)) were randomized to receive CAB (Arm A) or AR targeted therapy (Arm B, ABI or ENZ by investigator choice) with cross over at progression. No prior ABI or ENZ was permitted, but prior docetaxel allowed. Primary objective was to determine the clinical benefit rate (CBR) (PSA decline ≥50% (PSA50), objective response (OR), or stable disease (SD) ≥ 12 weeks). Other endpoints included time to PSA progression (TTPP), time to progression (TTP), and overall survival (OS). Serial plasma was sampled for circulating tumour DNA (ctDNA).

Results

95 pts were randomized (Arm A: 45, Arm B: 50). Poor prognosis was based on liver mets in 18%, early CRPC in 88%, and 30% by prognostic criteria. Other baseline factors: median age 68 years, elevated LDH in 41%, elevated ALK PHOS in 52%, ECOG PS 0-1 in 94%, 52% had prior docetaxel (half for castration sensitive disease). Median duration of therapy was 5.8 months (m) for Arm A and 4.5 m for Arm B. Treatment discontinuation reasons included disease progression (A vs B: 40% vs 46%) and toxicity (11% vs 4%). Outcomes are summarized in table. In 58 pts with available results, baseline ctDNA fraction >2% correlated with TTP (median 3.4 m vs 10.8 m, p = 0.011) and OS (median 15.5 m vs not reached (NR), p = 0.002). Genomic alterations in AR, RB1, TP53, PI3K pathway, and DNA repair were present in 69%, 36%, 51%, 40%, and 15%.

Arm A (CAB)Arm B (ABI/ENZ)HR (95% CI)P
CBR (%)82860.16
PSA50 (%)56600.68
OR (%)1112>0.90
SD > 12 weeks (%)62460.15
Median TTPP (m)7.44.80.73 (0.42-1.29)0.28
Median TTP (m)5.34.10.86 (.53-1.40)0.56
Median OS (m)NR15.50.56 (0.25-1.22)0.14

Conclusions

Treatment with CAB vs ABI/ENZA resulted in similar outcomes. There was a trend in favour of CAB for survival. Genomic correlations will be presented.

Clinical trial identification

NCT02254785.

Legal entity responsible for the study

Kim N. Chi and BC Cancer.

Funding

Sanofi Genzyme, Prostate Cancer Canada Movember Disxcovery Grant, Canadian Institutes of Health Research Project Grant, Terry Fox Research Institute Program Project Grant.

Disclosure

K.N. Chi: Honorarium, grant support: Sanofi Genzyme. N. Iqbal: Honorarium: Janssen, Astellas. M. Ong: Honorarium: Sanofi Genzyme, Janssen, Astellas. S.J. Hotte: Honorarium, advisory board, grant support: Janssen, Astellas. B. Tran: Consulting, honorarium, research grant support: Sanofi Genzyme, Janssen, Astellas. A. Azad: Honorarium: Sanofi, Janssen, Astellas; Grant: Astellas. S. North: Honorarium: Sanofi Genzyme, Janssen, Astellas. C.V. Pezaro: Honoraria, education support: Janssen, Astellas. S.S. Sridhar: Honorarium, grant support: Sanofi Genzyme, Janssen, Astellas. All other authors have declared no conflicts of interest.

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Proffered paper session - Genitourinary tumours, prostate Proffered Paper session

Invited Discussant 792O

Lecture Time
15:15 - 15:30
Speakers
  • Stéphane Oudard (Paris, FR)
Location
ICM - Room 13, ICM München, Munich, Germany
Date
19.10.2018
Time
14:00 - 15:30