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Displaying One Session

Mini Oral session
Date
Sun, 11.09.2022
Time
10:15 - 11:45
Location
7.3.Q - Quimper Auditorium
Chairs
  • Boris A. Hadaschik (Essen, Germany)
  • Martijn P. Lolkema (Rotterdam, Netherlands)
  • Nicolas Mottet (Saint-Étienne, France)
Session Type
Mini Oral session
Mini Oral session

1360MO - Quality of life and patient-relevant endpoints with darolutamide in the phase III ARASENS study

Presentation Number
1360MO
Speakers
  • Karim Fizazi (Villejuif, Cedex, France)
Lecture Time
10:15 - 10:20
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

In ARASENS, darolutamide (DARO) + androgen-deprivation therapy (ADT) + docetaxel significantly reduced risk of death by 32.5% vs placebo (PBO) + ADT + docetaxel (HR 0.68, 95% CI 0.57–0.80) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC). Given the potentially long treatment duration, the impact of DARO + ADT + docetaxel on pt-relevant endpoints is important to assess.

Methods

Pts were randomized 1:1 to DARO 600 mg twice daily or PBO + ADT + docetaxel. Pt-relevant endpoints were all-cause and prostate cancer related death; time course of adverse events (AEs) of special interest; and quality of life (QoL) based on time to worsening (TTW) of disease-related physical symptoms.

Results

In the safety analysis set (n=1302), the DARO + ADT + docetaxel arm (n=652) had fewer all-cause deaths (35.1% vs 46.8%) and prostate cancer related deaths (26.1% vs 36.0%) vs the PBO + ADT + docetaxel arm (n=650). Despite longer treatment exposure with DARO vs PBO (median 41.0 vs 16.7 months), overall AE incidence was similar in the 2 arms. Fatigue (DARO 33.1%, PBO 32.9%) and rash (16.6%, 13.5%) appeared predominantly in treatment months 1–3 and incidence decreased rapidly thereafter. Cumulative incidences of falls, fractures, and mental impairment were low (<10%) and similar between arms. The incidence of cardiac disorders was constant over time and similar between arms (DARO 10.9%, PBO 11.7%). Incidence of hypertension was 13.7% vs 9.2%, with similar distribution over time. Most pts had high baseline QoL scores that were maintained over time, with comparable TTW in both arms.

Population Events, n/N* (%) HR 95% CI
DARO PBO
Overall 351/651 (53.9) 308/654 (47.1) 1.04 0.89, 1.22
ALP ≥ULN 176/361 (48.8) 154/363 (42.4) 0.98 0.79, 1.22
Bone metastases 275/517 (53.2) 248/520 (47.7) 1.02 0.86, 1.21
Visceral metastases 59/111 (53.2) 54/118 (45.8) 1.04 0.72, 1.51
Baseline pain score >0 183/374 (48.9) 153/360 (42.5) 1.00 0.80, 1.24

Conclusions

Early treatment intensification with DARO + ADT + docetaxel improved pt-relevant endpoints, with reduced all-cause and prostate cancer related deaths and similar incidences and time course for most AEs of special interest vs PBO + ADT + docetaxel, notably with no increase in cardiac disorders. QoL was maintained over time, and DARO had no adverse impact on QoL, including in pts with poor prognosis.

Clinical trial identification

NCT02799602.

Editorial acknowledgement

Editorial assistance in the preparation of this abstract was provided by Sara Black of OPEN Health Communications, London, UK, with financial support from Bayer.

Legal entity responsible for the study

Bayer HealthCare.

Funding

Bayer HealthCare.

Disclosure

K. Fizazi: Financial Interests, Institutional, Funding, Consulting fees, Speakers Bureau, Ad Board: Amgen, Astellas, AstraZeneca, Bayer, Novartis, Sanofi, Janssen; Financial Interests, Personal, Other: Orion, Curvec; Financial Interests, Institutional, Funding: Lilly. M.R. Smith: Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Other, Consulting fees: Amgen, Bayer, Janssen, Lilly, Pfizer. M. Hussain: Financial Interests, Institutional, Funding: Bayer, Genentech, AstraZeneca; Financial Interests, Institutional, Advisory Board: Pfizer, Novartis, AstraZeneca/Merck, Janssen, Arvinas. F. Saad: Financial Interests, Institutional, Funding: Bayer, AstraZeneca, Astellas, Janssen, Merck, Novartis, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Bayer, AstraZeneca, Astellas, Janssen, Merck, Novartis, Pfizer; Non-Financial Interests, Other: Bayer, AstraZeneca, Astellas, Janssen, Merck, Novartis, Pfizer. C. Sternberg: Financial Interests, Institutional, Advisory Board: Bayer, MSD, Pfizer, Roche, AstraZeneca, Merck, Medscape, Astellas, Genzyme, Gilead, UroToday, Foundation Medicine, BMS, Impact Therapeutics. E.D. Crawford: Financial Interests, Institutional, Advisory Board: Janssen, Bayer, MDx, Tolmar; Financial Interests, Institutional, Invited Speaker: Genomic Health; Financial Interests, Institutional, Funding: NIH, Univ of Colorado Cancer Center; Financial Interests, Institutional, Speaker’s Bureau: Pfizer, Astellas; Financial Interests, Personal, Ownership Interest: 3rd Bx; Financial Interests, Institutional, Leadership Role: Carden Jennings. J.B. Aragon-Ching: Financial Interests, Personal, Advisory Role: Bayer, Janssen Oncology, Exelixis, Merck, Pfizer/EMD Serono, Immunomedics, AZD, Pfizer/Myovant; Financial Interests, Personal, Invited Speaker: BMS, Pfizer/EMD Serono, Astellas/Seagen. S. Thiele: Financial Interests, Personal, Full or part-time Employment: Bayer AG. S. Kapur: Financial Interests, Personal, Full or part-time Employment: Bayer SEA. A.F. Mohamed: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare. S. Srinivasan: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare. R. Li: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare. I. Kuss: Financial Interests, Personal, Full or part-time Employment: Bayer AG. H. Joensuu: Financial Interests, Personal, Full or part-time Employment: Orion Corporation Orion Pharma; Financial Interests, Personal, Stocks/Shares: Orion Corporation Orion Pharma, Sartar Therapeutics; Financial Interests, Institutional, Speaker’s Bureau: Neutron Therapeutics, Deciphera Pharmaceuticals. B. Tombal: Financial Interests, Institutional, Funding: Bayer, Ferring; Financial Interests, Institutional, Advisory Board: Bayer, Astellas, Amgen, Ferring, Janssen, Myovant, Novartis, Sanofi.

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Mini Oral session

LBA64 - Duration of androgen suppression with post-operative radiotherapy (DADSPORT): A collaborative meta-analysis of aggregate data

Presentation Number
LBA64
Speakers
  • Sarah Burdett (London, United Kingdom)
Lecture Time
10:20 - 10:25
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

The DADSPORT Meta-analysis Collaboration conducted a systematic review and meta-analysis of results from NRG/RTOG 9601, GETUG-AFU 16, NRG/RTOG 0534 and newly-available, RADICALS-HD trials to assess the effect of hormone therapy (HT) in men receiving radiotherapy (RT) following radical prostatectomy for localised prostate cancer.

Methods

We assessed the effects of adding HT to post-operative RT on overall survival (OS) and metastases-free survival (MFS), using published results and working with trialists to obtain additional data, including pre-publication results of RADICALS-HD. Primary analysis was a fixed-effect, inverse-variance meta-analysis, stratified by hormone duration (no HT, 6m and 24m of HT) following RT. A pre-specified sensitivity analysis excluded men from NRG/RTOG 9601 who had PSA >1.5ng/ml at randomisation.

Results

Based on all 4 eligible trials (701 deaths, 4452 men; 100% of all randomised), and median follow up ≥8 yrs, there was no clear improvement in OS with HT compared to no HT (HR 0.89, 95% CI 0.77-1.03). The effects on OS for 6m and 24m duration of HT versus no HT were similar, as were results of a sensitivity analysis to exclude men with PSA >1.5ng/mL (Table 1). Data on MFS from 2 trials of 24m HT vs no HT are not yet available. Based on data from 3 trials (653 events, 3364 men; 100%), there was evidence that 6m HT improved MFS compared to no HT (HR 0.82, 95% CI 0.70-0.96, p=0.013).

Results for overall survival

Treatment comparison No. of trials included No. of events/men Hazard ratio (HR) (95% CI), p-value Heterogeneity I 2 , p-value
HT (any duration) vs no HT 4 701/4452 0.89 (0.77-1.03), p=0.13 I2=0, p=0.42
HT (any duration) vs no HT:Sensitivity analysis 4 650/4334 0.93 (0.80-1.08), p=0.35 I2=0, p=0.67
6m HT vs no HT 3 419/3364 0.90 (0.74-1.09), p=0.28 I2=0, p=0.98
24m HT vs no HT 2 282/1088 0.89 (0.72-1.10), p=0.29 I2=74%, p=0.05
24m HT vs no HT:Sensitivity analysis 2 231/970 0.98 (0.78-1.23), p=0.87 I2=49%, p=0.16

Conclusions

We provide the most reliable evidence to date regarding the effects of HT with post-operative radiotherapy. Thus far, there is no clear evidence that the addition of HT improves OS, but 6m HT improves MFS. We aim to present updated results of the effects of HT on OS, MFS and prostate cancer-specific survival, including network meta-analysis incorporating all direct and indirect evidence, as well as effects by pre-defined patient subgroups.

Legal entity responsible for the study

The authors.

Funding

UK Medical Research Council.

Disclosure

C.C. Parker: Financial Interests, Institutional, Other, Lecture: Bayer; Financial Interests, Personal, Invited Speaker: Janssen; Non-Financial Interests, Personal, Advisory Board: Myovant, ITM Radiopharma; Financial Interests, Institutional, Advisory Board: AAA. M.R. Sydes: Financial Interests, Institutional, Funding: Astellas, Clovis Oncology, Janssen, Pfizer, Novartis, Sanofi-Aventis; Financial Interests, Personal, Training: Lilly Oncology, Janssen. A.U. Kishan: Financial Interests, Personal and Institutional, Funding: Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence ; Financial Interests, Personal and Institutional, Research Grant: Department of Defense, Radiological Society of North America, the STOP Cancer organization, the Jonsson Comprehensive Cancer Center, and the Prostate Cancer Foundation. C. Catton: Non-Financial Interests, Personal, Advisory Board: Bayer, AbbVie Corp; Financial Interests, Personal and Institutional, Funding: Tersera Corp. All other authors have declared no conflicts of interest.

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Mini Oral session

Invited Discussant 1360MO and LBA64

Speakers
  • Nicolas Mottet (Saint-Étienne, France)
Lecture Time
10:25 - 10:40
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45
Mini Oral session

1359MO - Differential treatment response with nodal metastases in metastatic hormone-sensitive prostate cancer (mHSPC) and evaluation of nodal (N) burden as a prognostic biomarker: Ancillary studies of the docetaxel and abiraterone acetate and prednisolone (AAP) phase III trials from STAMPEDE

Presentation Number
1359MO
Speakers
  • Áine M. Haran (Bath, United Kingdom)
Lecture Time
10:40 - 10:45
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

Better selection of patients (pts) for addition of docetaxel in mHSPC is required. Increased disease burden correlates with worse outcomes but nodal metastases have not been considered in metastatic volume definitions in mHSPC.

Methods

Overall survival (OS) was compared in subgroups of mHSPC pts (node +/- bone and bone-only), randomized 2:1 ADT +/- docetaxel or 1:1 ADT +/- AAP. Nodal burden was dichotomized into low (<5 nodes) and high (≥5 nodes) burden. Cox models were stratified by time period and adjusted for N stage, age (<70, ≥70), WHO PS, NSAID/aspirin use, radiotherapy (RT), bone metastases and CHAARTED low or high volume.

Results

1086 pts from ADT +/- docetaxel and 990 pts from ADT +/- AAP were studied. CT/MRI scans for 373 ADT +/- docetaxel and 602 ADT +/- AAP pts were also centralized and reviewed for nodal metastases. Significant OS benefit was demonstrated with ADT + AAP in both nodal +/- bone and bone-only metastases groups. Pts with bone-only metastases treated with ADT + docetaxel had a similar survival benefit. Notably, survival benefit was reduced for ADT + docetaxel in the nodal +/- bone metastases group. This difference was statistically significant by test for interaction (interaction HR 1.43, p=0.046). Higher nodal burden had significantly worse outcomes in both control arms and the research arm of ADT +/- AAP.

ADT/docetaxel HR (95% CI), p ADT/AAP HR (95% CI), p
Nodal +/-bone metastases 0.89 (0.74-1.07), 0.225 0.65 (0.53-0.78), <0.001
Bone only metastases 0.62 (0.46-0.84), 0.002 0.55 (0.41-0.74), <0.001
Prognostic evaluation of nodal burden
Control arm 1.67 (1.13-2.48), 0.011 1.45 (1.07-1.96), 0.016
Research arm 1.58 (0.94-2.67), 0.083 1.42 (1.02-1.98), 0.04

Conclusions

Increased nodal burden is a negative prognostic biomarker and should be considered in prospective risk/volume definitions to aid risk stratification in selected patients. We also demonstrate for the first time a potential differential response between mHSPC pts with nodal +/-bone metastases versus bone-only metastases for ADT + docetaxel but not for ADT + AAP.

Clinical trial identification

NCT00268476.

Legal entity responsible for the study

The Christie NHS Foundation Trust and the Medical Research Council Clinical Trials Unit at University College London.

Funding

Surgical Research Fund at The Christie NHS Foundation Trust.

Disclosure

All authors have declared no conflicts of interest.

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Mini Oral session

1361MO - 8-month PSA strongly predicts outcomes of men with metastatic castration-sensitive prostate cancer in the PEACE-1 phase III trial

Presentation Number
1361MO
Speakers
  • Gwenaëlle Gravis Mescam (Marseille, Cedex 09, France)
Lecture Time
10:45 - 10:50
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

Addition of abiraterone acetate plus prednisone (AAP) to androgen deprivation therapy (ADT) with or without docetaxel (D), improved overall survival (OS) in men with de novo metastatic castration sensitive prostate cancer (mCSPC) in the PEACE-1 phase 3 trial (Lancet 2022; April 8). The 8-months PSA decline to undetectable levels has been associated with improved OS and radiological progression-free survival (rPFS) in mCSPC men treated with ADT plus D or AAP. We assessed the association of 8-months PSA value with rPFS and OS in mCSPC men treated in PEACE-1 with the triplet systemic association: ADT+D+AAP.

Methods

It is a preplanned analysis of data from 1172 men receiving ADT+/- D +/- AAP. The analysis required a PSA at 8 months from ADT initiation. Data cut off was 1st June 2021. rPFS and OS were assessed overall, and then by randomization groups. The analysis was performed for the following 8-month PSA cut-offs: 0.2 and 4 ng/ml. Median values of rPFS and OS were calculated from 8 months-PSA using the Kaplan Meier method.

Results

PSA values at 8 months after ADT initiation were available in 931 men (79%). Standard of care was ADT + D in 62% and 56% had “high volume” disease. The median follow-up was 4.4 years (95% CI [4.3-4.5]). Results are in the table.

Treatment PSA < 0.2 ng/ml PSA >0.2* ng/ml PSA < 4 ng/ml PSA > 4* ng/ml
rPFS Median (year) [CI 95%] ADT+/- D n=439 4.0 [3.6-NR] 1.4 [1.2-1.7] 2.5 [2.0-3.1] 0.7 [0.5-1.0]
ADT + D n=286 3.7 [2.1-NR] 1.3 [1.1-1.5] 2.1 [1.7-3.0] 0.5 [0.4-1.0]
ADT+AAP +/- D n=441 NR [4.7-NR] 2.2 [1.6-2.9] 5.4 [4.1-NR] 0.7 [0.3-1.1]
ADT+AAP + D n=268 4.7 [4.5-NR] 2.5 [1.6-3.4] 4.5 [3.5-NR] 0.7 [0.3-1.2]
OS Median (year) [CI 95%] ADT +/- D n=471 NR [4.8-NR] 3.5 [3.1-4.1] 5.9 [4.7-NR] 2.1 [1.7-2.4]
ADT + D n=297 NR [4.0-NR] 3.5 [2.8-4.0]** 4.5 [4.0-NR] 2.1 [1.5-2.5]
ADT+AAP +/- D n=458 NR [5.7-NR] 3.4 [2.8-3.9] 6.1 [5.2-NR] 1.5 [0.9-1.9]
ADT+AAP + D n=276 NR [4.7-NR] 3.6 [2.9-NR] NR [4.7-NR] 1.6 [0.9-2.4]

∗p<.0001 ∗∗0.0007 NR: Not reach, CI: confidence interval.

Conclusions

8-month PSA value strongly predicts both rPFS and OS in men with mCSPC in PEACE-1. Early therapeutic intervention in men with unfavorable 8-month PSA values needs to be investigated.

Clinical trial identification

NCT01957436.

Legal entity responsible for the study

UNICANCER.

Funding

Janssen Pharmaceutical NV, Ipsen, Sanofi, French Academic Institution Financial support (PHRC).

Disclosure

G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: AAA, Alliance Merck-Pfizer, Astellas, BMS, Janssen, Pfizer, ipsen, alliance Merck Pfizer; Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Sanofi, Ipsen, AstraZeneca, BMS; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. G. Roubaud: Financial Interests, Personal, Invited Speaker: Astellas, Ipsen, Sanofi, Janssen. R.S. McDermott: Financial Interests, Personal, Advisory Board: Pfizer, Amgen, BMS, Bayer, Janssen, Clovis; Financial Interests, Personal, Invited Speaker: MSD, Ipsen, Astellas; Financial Interests, Institutional, Invited Speaker: MSD, Clovis, BMS, Regeneron, Bayer, Astellas. A. Flechon: Financial Interests, Personal, Expert Testimony: Sanofi, AstraZeneca, Astellas, Janssen, AAA, Bayer; Financial Interests, Personal, Invited Speaker: Novartis. B. Tombal: Financial Interests, Personal, Advisory Board: Astellas, Bayer, Amgen, Janssen, Sanofi, Myovant, Novartis (AAA), Pfizer, MSD, AstraZeneca; Financial Interests, Personal, Invited Speaker: Astellas, Amgen, Ferring; Financial Interests, Personal, Expert Testimony: Astellas; Non-Financial Interests, Invited Speaker, Past President: European Organisation of Research and Treatment of Cancer (EORTC); Non-Financial Interests, Invited Speaker, Education in the field of Oncology: ISSECAM. S. Supiot: Financial Interests, Personal, Invited Speaker: Bayer, Janssen, Astellas, Ipsen, Sanofi; Financial Interests, Personal, Leadership Role: Bayer; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Janssen, Astellas; Financial Interests, Personal, Project Lead: AstraZeneca, Janssen, Astellas. D.R. Berthold: Financial Interests, Institutional, Invited Speaker: Astellas, Janssen; Financial Interests, Institutional, Advisory Board: MSD, Ipsen, Bayer, BMS, Roche. G. Kacso: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Johnson & Johnson, Sanofi; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Officer: Amethyst; Financial Interests, Personal, Royalties: Astellas, AstraZeneca, Johnson & Johnson, Merck/ MSD, Novartis, Sanofi. F. Calabrò: Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca, Ipsen, Merck, Pfizer; Financial Interests, Institutional, Principal Investigator: Parexel, AstraZeneca, BMS, Syneos, MSD, PRA, IQVIA, Pfizer, J and J, Janssen, ICON, Roche, Eisai, Bayer. J.F. Berdah: Financial Interests, Personal, Invited Speaker: Janssen Cilag, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Astellas. A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Board, & public speaking: Pfizer, astrazeneca, Janssen, Ipsen, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Sanofi, Novartis, Roche/Genentech, MSD, Astellas Pharma; Financial Interests, Institutional, Funding: Pfizer, Ipsen, Bayer; Financial Interests, Institutional, Invited Speaker: Pfizer, AstraZeneca, Sanofi, JNJ, Novartis, Ipsen, Roche, BMS, MSD, Astellas Pharma, Excelixis, UNICANCER / GETUG, Incyte; Financial Interests, Invited Speaker: AstraZeneca, Novartis, BMS; Non-Financial Interests, Member: ASCO, GETUG; Other, Travel, Accommodations: Roche, MSD, JNJ, BMS, AstraZeneca, Pfizer, Astellas Pharma, Ipsen. A. Rodriguez-Vida: Financial Interests, Personal, Invited Speaker: Roche, MSD, Pfizer, BMS, Astellas, Janssen, Bayer, Clovis, AstraZeneca, Sanofi; Financial Interests, Personal, Principal Investigator: Takeda, Pfizer, Merck. K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. All other authors have declared no conflicts of interest.

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Mini Oral session

Invited Discussant 1359MO and 1361MO

Speakers
  • Boris A. Hadaschik (Essen, Germany)
Lecture Time
10:50 - 11:05
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45
Mini Oral session

LBA65 - SAKK 08/14 - IMPROVE Investigation of metformin in patients with metastatic castration-resistant prostate cancer (mCRPC) in combination with enzalutamide vs. enzalutamide alone. A randomized, open label, phase II trial

Presentation Number
LBA65
Speakers
  • Christian A. Rothermundt (St. Gallen, Switzerland)
Lecture Time
11:05 - 11:10
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

Enzalutamide (ENZ) is a standard treatment for mCRPC patients (pts) who progress on androgen deprivation therapy (ADT). Metformin (MF) is an oral medication for diabetes mellitus (DM). MF has both indirect and direct effects on tumour growth. In a phase 2 study, MF induced PSA responses and disease stabilization in non-diabetic mCRPC pts. Some epidemiological data suggest a benefit of MF in prostate cancer pts. There is preclinical data on synergism of ENZ and MF. The purpose of this trial is to test if ENZ + MF in pts with mCRPC progressing on ADT is more effective compared to ENZ alone.

Methods

SAKK 08/14 is a prospective multicenter, 1:1 randomized, open label, phase 2 trial. Pts with mCRPC progressing on ADT and no prior or current therapy for DM were eligible. Pts received ENZ 160mg OD alone or in combination with MF 850mg BID. The primary endpoint of the trial is disease control rate (DCR) at 15 months (mos), defined as at least stable disease maintained during trial treatment for at least 15 mos. Secondary endpoints include OS, EFS, time to PSA progression (TTPSAP), adverse events and quality of life. In order to show superiority for ENZ + MF a total of 168 evaluable pts were needed to detect a 20% difference in DCR at 15 mos (type I error 10%, power 80%).

Results

169 pts were accrued from 06/2016 - 02/2021 in 15 Swiss centers. Median follow-up was 44 mos (95%CI 39.0-48.7). The primary endpoint was not met: DCR at 15 mos was 52.4% for ENZ + MF and 56.1% for ENZ, respectively (p=0.644). There was a trend towards improved median EFS for ENZ + MF vs ENZ (19.3 (12.5, 28.1) vs. 15.1 (12.1, 21.4) mos; HR 0.87 (95%CI 0.60-1.26; p = 0.471)), median TTPSAP (15.8 (11.4, 20.6) vs. 11.0 (9.4, 13.2) mos; HR 0.71 (95%CI 0.49-1.04; p = 0.074)) and median time to pain progression (41.7 (16.9, NA) vs. 20.3 (14.2, 58.4) mos, p = 0.474)). Median OS was similar in both arms (38.7 (25.9, 50.0) and 40.9 (28.3, 51.7) mos; HR 1.13 (0.74, 1.71); p = 0.575).

Conclusions

This is the first randomized study to investigate ENZ + MF in mCRPC and it was negative for the primary endpoint. However, MF may have a modest effect on PSA dynamics and symptom control. Larger studies are needed for confirmation.

Clinical trial identification

NCT02640534.

Legal entity responsible for the study

Swiss Group for Clinical Cancer Research (SAKK).

Funding

Astellas.

Disclosure

C.A. Rothermundt: Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Board: Bristol-Myers Squibb, MSD Oncology, Bayer (Schweiz) AG, IPSEN; Financial Interests, Personal, Expert Testimony: Merck; Financial Interests, Institutional, Other, Travel Costs: PharmaMar; Financial Interests, Institutional, Sponsor/Funding: Astellas. R. Cathomas: Financial Interests, Institutional, Advisory Board: Bayer, Janssen, Astellas, Sanofi, Pfizer, MSD, BMS, Roche, Merck, Debiopharm; Financial Interests, Institutional, Advisory Role: Novartis. S.I. Rothschild: Financial Interests, Institutional, Advisory Role: Amgen, AstraZeneca, Bayer, BMS, Boehringer-Ingelheim, Eisai, Eli Lilly, Merck Serono, MSD, Novartis, Otsuka, Pfizer, PharmaMar, Roche Pharma, Roche Diagnostics, Sanofi Aventis, Takeda; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Merck, Roche Pharma, AbbVie, BMS, Boehringer-Ingelheim, Foundation Medicine; Financial Interests, Institutional, Other, Honoraria: Amgen, AstraZeneca, BMS, MSD Oncology, Novartis, Roche Pharma, Roche Diagnostics, Takeda; Financial Interests, Institutional, Expert Testimony: AstraZeneca, BMS, Roche Pharma; Financial Interests, Institutional, Other, Travel and Accomodation: Amgen, AstraZeneca, BMS, Eli Lilly, MSD, Roche, Takeda, Boehringer-Ingelheim; Non-Financial Interests, Personal, Leadership Role: Vice President of the Swiss Group for Clinical Cancer Research (SAKK); Non-Financial Interests, Personal, Member: Federal Drug Commission of the Federal Office of Public Health; Financial Interests, Institutional, Advisory Board: AbbVie, Astellas, Janssen; Financial Interests, Institutional, Invited Speaker: Janssen, Sanofi. S. Gillessen: Financial Interests, Personal, Advisory Board: Amgen, MSD, Orion; Financial Interests, Personal, Other, Honoraria: Radio-televisione Svizzera Italiana (RSI), German-speaking European School of Oncology (DESO); Financial Interests, Personal, Invited Speaker: ESMO, wiss group for Clinical Cancer Research (SAKK), Swiss Academy of Multidisciplinary oncology (SAMO), Orikata academy research group, China Anti-Cancer Association Genitourinary Oncology Committee (CACA-GU); Financial Interests, Personal, Speaker’s Bureau: Janssen Cilag; Financial Interests, Personal, Other, Travel Grant: ProteoMEdiX, AstraZeneca; Financial Interests, Institutional, Advisory Board: AAA International, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Modra Pharmaceuticals, MSD, Myriad Genetic, Novartis, Orion, Pfizer, Roche, Telixpharma Tolero Pharmaceutcials; Financial Interests, Institutional, Other, Honoraria: Silvio Grasso Consulting, WebMD-Medscape; Financial Interests, Institutional, Royalties: WO2009138392. All other authors have declared no conflicts of interest.

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Mini Oral session

1362MO - Pembrolizumab + olaparib vs abiraterone (abi) or enzalutamide (enza) for patients (pts) with previously treated metastatic castration-resistant prostate cancer (mCRPC): Randomized open-label phase III KEYLYNK-010 study

Presentation Number
1362MO
Speakers
  • Evan Y. Yu (Seattle, United States of America)
Lecture Time
11:10 - 11:15
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

There is unmet need for effective therapies for pts with heavily pretreated mCRPC. KEYLYNK-010 (NCT03834519) evaluated efficacy and safety of pembrolizumab (P) + olaparib (O) vs abi or enza for molecularly unselected pts with mCRPC after a next-generation hormonal agent (NHA) and docetaxel.

Methods

Eligible pts were ≥18 yrs; had mCRPC that progressed on or after abi or enza (but not both) as well as docetaxel; had ECOG PS ≤1. Pts were randomized 2:1 to 200 mg P IV Q3W for ≤35 cycles + 300 mg O orally BID, or to NHA: 1000 mg abi orally QD (if prior enza) or 160 mg enza orally QD (if prior abi). Dual primary endpoints were radiographic PFS (rPFS) by blinded independent central review (BICR) per PCWG-modified RECIST 1.1 (final testing at first interim analysis [IA1]), and OS (final testing at IA2). Secondary endpoints included ORR by BICR per PCWG-modified RECIST 1.1 and safety/AEs.

Results

793 pts were randomized to P + O (n=529) or NHA (n=264) between May 30, 2019 and July 16, 2021. The KEYLYNK-010 study was stopped for futility. As of Jan 18, 2022, median (range) follow-up for IA2 was 11.9 mo (0.9–31.0). Baseline characteristics were balanced between arms. The primary endpoints of rPFS (median 4.4 mo with P + O vs 4.2 mo with NHA; HR 1.02, 95% CI 0.82−1.25; P=0.55) and OS (15.8 mo vs 14.6 mo; HR 0.94, 95% CI 0.77−1.14; P=0.26) were not met. ORR was 17% with P + O vs 6% with NHA (nominal P=0.002). Exploratory analysis of subgroups by tissue-based homologous recombination repair gene alteration (HRRm) at IA2 suggested a potential difference in rPFS (HRRm [P + O n=81, NHA n=37]: HR 0.53, 95% CI 0.33–0.86; non-HRRm [P + O n=246, NHA n=118]: HR 1.19, 95% CI 0.90–1.58) but not in OS (HRRm: HR 0.91, 95% CI 0.53–1.56; non-HRRm: HR 1.03, 95% CI 0.77–1.38). Gr ≥3 TRAEs occurred in 35% of pts with P + O and 9% of pts with NHA; 5% and 1% of pts, respectively, had gr ≥3 immune-mediated AEs.

Conclusions

Pembrolizumab + olaparib did not improve rPFS or OS in the unselected population despite a higher ORR. While pembrolizumab + olaparib resulted in more gr ≥3 TRAEs vs NHA in pts with previously treated mCRPC, no new safety signals occurred.

Clinical trial identification

KEYLYNK-010, NCT03834519.

Editorial acknowledgement

Writing assistance was provide by Ina Nikolaeva of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

E.Y. Yu: Financial Interests, Personal, Advisory Board: AbbVie, Advanced Accelerator Applications, Bayer, Clovis, Exelixis, Janssen, Merck, Genzyme; Financial Interests, Institutional, Research Grant: Bayer, Blue Earth, Daiichi Sankyo, Dendreon, Lantheus, Merck, Seagen, Taiho. J.C.H. Goh: Financial Interests, Personal, Advisory Board, Prior member of the BMS RCC Advisory Board: BMS; Financial Interests, Personal, Advisory Board, Uterine Cancer Advisory Board: GSK; Financial Interests, Personal, Other, Chairing RCC meeting: Ipsen; Financial Interests, Personal, Invited Speaker, Speaking at MSD sponsored event on Gynaecological cancer: MSD; Financial Interests, Personal, Advisory Board, Met RCC Advisory Board: MSD/ Eisai; Financial Interests, Personal, Other, Asia-Pacific Advisory Board member for prostate cancer: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Private Cancer Centres in Australia: ICON Cancer Centres; Financial Interests, Institutional, Funding, Funding for phase 2 metastatic cervical cancer trial: BeiGene; Non-Financial Interests, Principal Investigator, local PI for CHECKMATE-914, CHECKMATE-9KD trial, CHECKMATE-7DX & CHECKMATE-9ER trials: BMS. N. Mehra: Financial Interests, Personal, Advisory Board: Pfizer, Roche, MSD, AstraZeneca, Astellas, JNJ; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Funding: Astellas, Pfizer; Financial Interests, Personal and Institutional, Funding: Janssen; Financial Interests, Institutional, Invited Speaker: BMS, Janssen, BMS; Financial Interests, Institutional, Research Grant: AstraZeneca, BMS; Non-Financial Interests, Leadership Role, Head of the Prostate Cancer Working group: Dutch Uro-Oncology Study Group; Non-Financial Interests, Principal Investigator, Co-PI: Prospective Bladder Cancer Infrastructure (Netherlands); Non-Financial Interests, Leadership Role: Castration-resistant Prostate Cancer Registry. R. McDermott: Financial Interests, Personal, Advisory Board: Amgen, Bayer, BMS, Clovis, Janssen, Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, Ipsen, MSD; Financial Interests, Institutional, Principal Investigator: Astellas, Bayer, BMS, Clovis, MSD, Regeneron. M.A. Sala Gonzalez: Non-Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Advisory Board: AstraZeneca. P.C. Fong: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Other, Oncology meeting attendance/Accommodation: Pfizer; Non-Financial Interests, Advisory Role: New Zealand Prostate Cancer Foundation. R. Greil: Financial Interests, Personal, Other: Celgene, Roche, Merck, Takeda, AstraZeneca Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche , BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Institutional, Research Grant: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie Gilead, Daiichi Sankyo; Financial Interests, Personal, Funding: Roche, Amgen, Janssen, AstraZeneca Novartis, MSD, Celgene, Gilead, BMS, AbbVie, Daiichi Sankyo. Y. Huang: Financial Interests, Personal, Invited Speaker: Astellas, BMS, Ipsen, Janssen, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Board: Astellas, Bayer. S. Begbie: Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Principal Investigator: Merck; Financial Interests, Institutional, Research Grant: MSD, Merck; Financial Interests, Institutional, Principal Investigator: MSD, Merck. F. Rey: Financial Interests, Institutional, Funding: MSD. G. Kramer: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, BMS, Ipsen, Janssen, MSD, Novartis, Sanofi Genzyme, Takeda, Ferring. H. Suzuki: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca, MSD, Takeda, Sanofi, Bayer; Financial Interests, Personal, Advisory Board: Janssen, Astellas, AstraZeneca, MSD, Takeda, Sanofi, Bayer, Chugai-Roche, Eli Lilly; Financial Interests, Institutional, Research Grant: Takeda, Astellas, Bayer, AstraZeneca, MSD, Chuga-Roche, Nippon Shinyaku, Nihon Kayaku. J. Zhang: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. J. Kim: Financial Interests, Institutional, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Institutional, Stocks/Shares: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. C.H. Poehlein: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; Financial Interests, Personal, Research Grant: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. E.S. Antonarakis: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Sanofi, Dendreon, Bayer, BMS, Amgen, ESSA, Constellation, Blue Earth, Exact Sciences, Invitae, Curium, Pfizer, AstraZeneca, Clovis, Eli Lilly; Financial Interests, Personal, Research Grant: Janssen, J&J, Sanofi, BMS, Pfizer, Novartis, Curium, Constellation, ESSA, Celgene, Merck, Bayer, Clovis. All other authors have declared no conflicts of interest.

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Mini Oral session

1363MO - Cabazitaxel every 2 weeks versus every 3 weeks in older patients with metastatic castration-resistant prostate cancer (mCRPC): The CABASTY randomized phase III trial

Presentation Number
1363MO
Speakers
  • Stephane Oudard (Paris, France)
Lecture Time
11:15 - 11:20
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

Cabazitaxel 25 mg/m2 every 3 weeks (CBZ q3w) + G-CSF prolongs overall survival (OS) vs abiraterone or enzalutamide in mCRPC patients (pts) previously treated with docetaxel (DOC) and the alternative androgen-targeted agent (ART) ( De Wit, NEJM 2019 ). CBZ 16 mg/m2 every 2 weeks (CBZ q2w) induces less severe neutropenia and could be useful for older pts unfit to receive CBZ q3w ( Clément-Zhao, BJU Int 2018 ).

Methods

Pts with progressive mCRPC (≥65 yrs, ECOG 0-2, G8 >14 or ≤14 with reversible geriatric impairment) previously treated with DOC were randomized to CBZ q3w + prednisone (P) + G-CSF vs CBZ q2w + P + G-CSF and stratified by age (<70 vs ≥ 70 yrs) and G8 (>14 vs ≤14). Primary endpoint was the percentage of pts with grade ≥3 neutropenia and/or neutropenic complications (febrile neutropenia, neutropenic infection, sepsis). Secondary endpoints were radiographic progression-free survival (rPFS), objective tumor response, skeletal related events (SREs), PSA response, quality of life (not reported here), safety and OS.

Results

Overall, 196 pts (median age, 74.0 yrs; ≥ 70 yrs, 79.6%; G8 <14, 19.9%; vulnerable or frail per SIOG guidelines, 30.1%; prior ART, 86.7%) were randomized (CBZ q3w, n=97; CBZ q2w, n=99). Relative dose intensity for CBZ 3qw vs CBZ 2qw was comparable (92.3% vs 91.6%). Rate of Grade ≥3 neutropenia and/or neutropenic complications was significantly higher with CBZ q3w vs CBZ q2w (62.9% vs 5.1%; Odds Ratio = 0.03 [95% CI 29.5-48.9], p<0.001). Grade ≥3 adverse events were more common with CBZ 3qw (72.9% vs 58.2%). One patient (CBZ q3w arm) died of neutropenic complication. No new safety signal was observed. Main secondary criteria are provided below.

CBZ q3w (n=97) CBZ q2w (n=99) P-value
Median OS, months 14.1 14.0 0.39
Median rPFS, months 6.3 6.7 0.82
PSA response ≥ 50% 45.2% 42.9% 0.75
Objective tumor response 18.1% 15.4% 0.63
No SRE at 1 year 87.4% 79.7% 0.81

Conclusions

Compared to standard regimen, CBZ q2w plus G-CSF significantly reduced the occurrence of grade ≥3 neutropenia and/or neutropenic complications with comparable clinical outcomes. CBZ q2w regimen could become a practice changing therapy for elderly mCRPC pts.

Clinical trial identification

NCT02961257, EudraCT 2016-001179-60.

Legal entity responsible for the study

ARTIC.

Funding

Sanofi.

Disclosure

S. Oudard: Financial Interests, Personal, Advisory Board, Consultancy, Advisory Role: Sanofi; Financial Interests, Personal, Invited Speaker, Public Speaking and Advisory Role: Janssen; Financial Interests, Personal, Advisory Board, Advisory Role and Public Speaking: AstraZeneca, MSD, Merck, Astellas, Ipsen, Pfizer, Roche, Genentech; Financial Interests, Personal, Advisory Board, Advisory Board and Public Speaking: BMS, Bayer, Novartis. A. Thiery-Vuillemin: Financial Interests, Personal, Advisory Board, & Public Speaking: Pfizer, AstraZeneca, Janssen, Ipsen, Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Sanofi, Novartis, Roche/Genentech, MSD, Astellas Pharma; Financial Interests, Institutional, Funding: Pfizer, Ipsen, Bayer; Financial Interests, Institutional, Invited Speaker: Pfizer, AstraZeneca, Sanofi, JNJ, Novartis, Ipsen, Roche, BMS, MSD, Astellas Pharma, Excelixis, UNICANCER / GETUG, Incyte; Financial Interests, Invited Speaker: AstraZeneca, Novartis, BMS; Non-Financial Interests, Member: ASCO, GETUG; Other, Travel, Accommodations: Roche, MSD, JNJ, BMS, AstraZeneca, Pfizer, Astellas Pharma, Ipsen. C. Saldana: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Ipsen, Pfizer. G. Von Amsberg: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Astellas, Sanofi, Ipsen, Janssen, MSD, AstraZeneca, Merck, EISAI, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Astellas, Sanofi, Ipsen, EISAI, MSD, Janssen, AstraZeneca, Merck, Bayer, Bayer, Ferring, Janssen, Ipsen, BMS, Pfizer, Amgen; Financial Interests, Institutional, Invited Speaker: Pfizer, Sanofi, Bristol Myers Squibb, Roche, MSD, Exelixis, AstraZeneca, AvenCell, Ipsen. S. Feyerabend: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Bayer, Aventis; Other, Honorarium: Janssen; Financial Interests, Personal, Other, Travel and accommodation expenses: Aventis. D. Pfister: Financial Interests, Personal, Invited Speaker: Sanofi, Janssen, MSD, Bayer, AstraZeneca, Merck; Financial Interests, Personal, Advisory Board: Janssen, MSD, Pfizer; Financial Interests, Personal, Other, Consultant: MSD. M. Schostak: Financial Interests, Personal, Other, Consultant: AstraZeneca, BMS, EDAP-TMS, Janssen, Merck, Merck-sharp&dohme; Financial Interests, Personal, Other, Honoraria and travel costs: Amgen, AstraZeneca, Bayer-Vital, BMS, EDAP-TMS, Pfizer, Janssen, NewConcept, Novartis; Financial Interests, Personal, Other, Travel Costs: Deutsche Krebsgesellschaft, Deutsche Gesellschaft für Radioonkologie, Deutsche Gesellschaft für Radiologie, Deutsche Gesellschaft für Urologie, Ipsen; Financial Interests, Institutional, Funding, Funding of scientific projects: AstraZeneca, Bayer-Vital, BMS, AUO, Clinical Laserthermia Systems AB, EDAP-TMS, Ferring, Ipsen, Janssen, Merck, Merck Sharp&Dohme, Parexel. O. Huillard: Financial Interests, Personal, Invited Speaker: Sanofi, Ipsen, Novartis; Financial Interests, Personal, Advisory Board: Janssen, Bristol Myers Squibb, AstraZeneca, Pfizer, Eisai, Bayer. C. Helissey: Financial Interests, Personal, Invited Speaker: Janssens, Roche, Astellas, AstraZeneca, Sanofi; Non-Financial Interests, Principal Investigator: Janssen, Sanofi, Roche, Astellas. All other authors have declared no conflicts of interest.

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Mini Oral session

1364MO - Preliminary phase II results of the CYPIDES study of ODM-208 in metastatic castration-resistant prostate (mCRPC) cancer patients

Presentation Number
1364MO
Speakers
  • Karim Fizazi (Villejuif, Cedex, France)
Lecture Time
11:20 - 11:25
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45

Abstract

Background

ODM-208 is a first in class, oral, non-steroidal, and selective inhibitor of CYP11A1, the first and rate-limiting enzyme of steroid biosynthesis. ODM-208 suppresses the production of all steroid hormones and precursors that may activate the androgen receptor (AR) signalling pathway. This is particularly relevant in patients with AR ligand binding domain (LBD) activating somatic point mutations, a mechanism of resistance to hormone-based therapies in mCRPC. We report the first results of the phase 2 expansion of the CYPIDES trial.

Methods

ODM-208 5mg BID (with dexamethasone and fludrocortisone) was evaluated in an open-label expansion cohort in patients with progressing mCRPC who had previously received ≥1 line of 2nd generation AR pathway inhibitor and ≥1 line of taxane-based chemotherapy. All patients had a pre-specified activating AR LBD mutation by pre-screening of cell-free DNA (Guardant 360). Study objectives were safety and preliminary efficacy assessed by PSA and RECIST response and standard safety measures. ODM-208 treatment was continued until subsequent disease progression. The study was conducted at 18 sites in France, Finland, UK and USA.

Results

81 of 390 (20.8%) pre-screened patients had a pre-specified AR LBD mutation, of which 45 patients (median age 68 yrs) were enrolled and initiated ODM-208 treatment (43 at data cut-off 17 March 2022). 51% patients had previously received both abiraterone and enzalutamide, and 65% patients both docetaxel and cabazitaxel. Based on the emerging data ODM-208 profoundly suppressed androgen synthesis resulting in >50% best PSA reduction in more than 50% patients and at least 4 RECIST partial responses in 17 evaluable patients (data immature). ODM-208 has been well-tolerated with a much lower rate of hospitalisation for adrenal insufficiency than in phase 1 with typically higher doses (2.3% vs. 33% to date). Efficacy and safety data will be presented for the complete cohort with at least 5 months follow-up for all patients.

Conclusions

Administration of ODM-208 to heavily pre-treated mCRPC patients with AR LBD mutation was highly effective in blocking the production of steroid hormones and showed promising antitumor activity. NCT03436485.

Clinical trial identification

NCT03436485.

Legal entity responsible for the study

Orion Corporation.

Funding

Orion Corporation.

Disclosure

K. Fizazi: Financial Interests, Institutional, Advisory Board: Astellas, Bayer, Janssen, AAA, MSD, AstraZeneca, Novartis/AAA, Pfizer; Financial Interests, Institutional, Invited Speaker: Astellas, Bayer, Janssen, Sanofi, MSD, AstraZeneca, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Curevac, Orion; Financial Interests, Institutional, Research Grant, Trial chair: Pfizer, Bayer, AstraZeneca, Orion, MSD, BMS, Janssen; Non-Financial Interests, Principal Investigator, Chair of the 7DX phase 3 trial: BMS; Non-Financial Interests, Principal Investigator, Chair of the Docetaxel-pembrolizumab phase 3 trial: Merck; Non-Financial Interests, Principal Investigator, Chair of the Darolutamide BCR phase 3 trial: Bayer; Non-Financial Interests, Principal Investigator, Chair of the PSMAfore phase 3 trial: AAA/Novartis; Non-Financial Interests, Principal Investigator, Chair of the CYPIDES ODM-208 Phase I-II trial: Orion; Non-Financial Interests, Principal Investigator, Chair of the STESIDES ODM-209 Phase I-II trial: Orion. A. Bernard-Tessier: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Other, travel fees: Orion, Bayer; Financial Interests, Institutional, Advisory Board: Novartis; Non-Financial Interests, Principal Investigator: Amgen. P. Barthelemy: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck, Pfizer, Ipsen, Bayer, Janssen Cilag, Astellas, Novartis, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Seagen. T. Utriainen: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Orion. A. Flechon: Financial Interests, Personal, Expert Testimony: Sanofi, AstraZeneca, Astellas, Janssen, AAA, Bayer; Financial Interests, Personal, Invited Speaker: Novartis. G. Gravis Mescam: Financial Interests, Institutional, Advisory Board: AAA, Alliance Merck-Pfizer, Astellas, BMS, Janssen, Pfizer, Ipsen, alliance Merck Pfizer; Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Sanofi, Ipsen, AstraZeneca, BMS; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. R. Ratta: Financial Interests, Personal, Invited Speaker: Ipsen, Astellas; Financial Interests, Personal, Advisory Board: Pfizer, Merck, Bristol Meyer Squibb, AstraZeneca. M.M.E. Tanner: Financial Interests, Personal, Advisory Board: Roche Finland, Pfizer, Novartis, Lilly, AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Novartis, Roche Finland, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Novartis, Roche, AbbVie, Boehringer Ingelheim, Orion. C. Garratt: Financial Interests, Personal, Full or part-time Employment: Orion Pharma UK Ltd.; Financial Interests, Personal, Stocks/Shares: Orion Corporation. P. Pohjanjousi: Financial Interests, Personal, Full or part-time Employment: Orion. T. Ikonen: Financial Interests, Personal, Full or part-time Employment: Orion. E.S. Antonarakis: Financial Interests, Institutional, Advisory Role: Janssen, Astellas, Sanofi, Dendreon, Bayer, BMS, Amgen, ESSA, Constellation, Blue Earth, Exact sciences, Invitae, Curium, Pfizer, Merck, AstraZeneca, Clovis, Eli Lilly; Financial Interests, Institutional, Research Grant: Janssen, J&J, Sanofi, BMS, Pfizer, AstraZeneca, Novartis, Curium, Constellation, ESSA, Celgene, Merck, Bayer, Clovis. N. Cook: Financial Interests, Institutional, Invited Speaker: Roche, Taiho, Roche, AstraZeneca, RedX, Orion, Avacta, Bayer, Eisai, UCB, Starpharma, Boehringher, Stemline, Ergomed; Non-Financial Interests, Advisory Role: Roche. All other authors have declared no conflicts of interest.

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Mini Oral session

Invited Discussant LBA65, 1362MO, 1363MO and 1364MO

Speakers
  • Martijn P. Lolkema (Rotterdam, Netherlands)
Lecture Time
11:25 - 11:40
Location
7.3.Q - Quimper Auditorium, Paris Expo Porte de Versailles, Paris, France
Date
Sun, 11.09.2022
Time
10:15 - 11:45