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Mini Oral - Genitourinary tumours, prostate

614MO - Cabazitaxel (CBZ) activity in men with metastatic castration resistant prostate cancer (mCRPC) with and without DNA damage repair (DDR) defects

Date

18 Sep 2020

Session

Mini Oral - Genitourinary tumours, prostate

Presenters

Mihaela Aldea

Citation

Annals of Oncology (2020) 31 (suppl_4): S507-S549. 10.1016/annonc/annonc275

Authors

M. Aldea1, L. Lam2, C. Llacer Perez3, M. Saint-Ghislain4, G. Gravis Mescam5, A. Fléchon6, G. Roubaud7, P. Barthélémy8, F. Ricci9, F. Priou10, Z.M. Neviere11, M. Beaufils5, C. Helissey12, R. Ratta13, C. Pobel14, E. Castro Marcos15, A. Thiery-Vuillemin16, G. Baciarello1, E. Orillard16, K. Fizazi1

Author affiliations

  • 1 Medical Oncology, Institut Gustave Roussy, University of Paris Saclay, 94805 - Villejuif/FR
  • 2 Biostatistics And Epidemiology, Institut Gustave Roussy, University of Paris Saclay, 94800 - Villejuif/FR
  • 3 Medical Oncology Department, Hospital Universitario Virgen de la Victoria, 29010 - Malaga/ES
  • 4 Medical Oncology, Centre Francois Baclesse, 14000 - Caen/FR
  • 5 Medical Oncology, Institute Paoli Calmettes, 13009 - Marseille/FR
  • 6 Department Of Medical Oncology, Centre Léon Bérard, Lyon/FR
  • 7 Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 8 Department Of Medical Oncology, Les Hôpitaux Universitaires de Strasbourg/ Institut de Cancérologie Strasbourg Europe, Strasbourg/FR
  • 9 Medical Oncology, Institut Curie, 75005 - Paris/FR
  • 10 Medical Oncology, CHD Vendee - Hopital Les Oudairies, 85925 - La Roche sur Yon/FR
  • 11 Medical Oncology, Centre Francois Baclesse, 14076 - Caen/FR
  • 12 Medical Oncology, Bégin Military Teaching Hospital, 94160 - Saint-Mandé/FR
  • 13 Medical Oncology, Hôpital Foch, 92150 - Suresnes/FR
  • 14 Medical Oncology, Hôpital européen Georges-Pompidou, 75015 - Paris/FR
  • 15 Medical Oncology, Hospital Universitario Virgen de la Victoria; Instituto de Investigación Biomédica de Málaga, 29010 - Málaga/ES
  • 16 Medical Oncology Department, University Hospital Jean Minjoz, 25000 - Besancon/FR
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Resources

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Abstract 614MO

Background

Up to 30% of mCRPC men harbor DDR defects and may benefit from PARP inhibitors (PARPi) after abiraterone/enzalutamide and docetaxel failure. CBZ was recently shown to improve overall survival (OS) in this population, though benefit by DDR status is unknown. We assessed CBZ activity in men with mCRPC according to their DDR status.

Methods

In this retrospective multicenter study, mCRPC patients (pts) who received CBZ were included if their DDR profile from tissue was available. Gene panels included at least BRCA1/2, ATM, CDK12 CHEK1/2, FANCA/FANCL, PALB2, RAD51. DDR positive (DDR+) pts could have had any deleterious germline or somatic DDR. For each DDR+ pts, DDR negative (DDR-) pts were randomly selected after matching for the same molecular test and institution, in a 1:1 ratio. PSA decline, radiological progression-free survival (rPFS) and OS were assessed.

Results

A total of 190 pts were included: 95 DDR+ and 95 DDR-. DDR+ pts were younger than DDR- (66 vs 69 years, p=0.026). The Gleason score was ≥8 in 66% and 55%, metastases (mts) were found at diagnosis in 51% and 41%, respectively. At CBZ start, pts had received a median of 2 prior life-prolonging agents, visceral mts in 24% and 26%, ECOG ≤1 in 78% and 80%, and a median PSA of 91 and 77 ng/ml, respectively. Among DDR+ pts, 40 (42%) had BRCA defects and 43 (45%) received a PARPi. A 50% PSA decline was achieved with CBZ in 29 (32%) and 33 (36%) in DDR+ and DDR- pts (p=0.64). Median rPFS was 5.33 months [95%CI 4.34-7.04] and 5.75 months [95%CI 4.67-7.27] (p=0.55), and median OS was 15.4 months [95%CI 12.16-26.6] and 11.5 months [95%CI 9.76-14.4] (p=0.036), respectively. An ECOG≥2 and visceral mts were independently associated with shorter OS. Outcomes of DDR+ pts are depicted in the Table, according to their sequence with PARPi. Table: 614MO

CBZ no PARPi n=53 CBZ before PARPi n=24 CBZ after PARPi n=18
Median prior lines 2 2 3
ECOG ≤1 36/53 (72%) 22/24 (92%) 12/18 (67%)
Visceral mts 13/53 (25%) 5/24 (21%) 4/18 (22%)
50% PSA decline All pts BRCA+ 16/51 (31%) 10/39 (26%) 10/24 (42%) 6/14 (43%) 3/18 (17%) 0/10 (0%)
Median rPFS (months) [95%CI] 6.15 [3.68-8.38] 5.97 [3.98-8.05] 3.09 [0.98-6.57]
Median OS (months) [95%CI] 12.9 [10.2-20] 42.5 [20.2-67.4] 7.2 [5.29-13.41]

Conclusions

CBZ is active in both DDR+ and DDR- mCRPC men. Activity may be lower in pts pre-treated with a PARPi, pending validation.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Karim Fizazi.

Funding

Has not received any funding.

Disclosure

C. Llacer Perez: Travel/Accommodation/Expenses: Astellas Pharma, Angelini Pharma. G. Gravis Mescam: Honoraria (institution): Pfizer, BMS, MSD, AstraZeneca, Astellas, Janssen, Bayer; Advisory/Consultancy: BMS, Pfizer, AstraZeneca, Janssen, Sanofi, Ipsen, Bayer; Travel/Accommodation/Expenses: BMS, Pfizer, AstraZeneca, Janssen, Sanofi, Ipsen, MSD. A. Fléchon: Honoraria (self): AZ Sanofi, Astellas, Janssen AAA; Travel/Accommodation/Expenses: AZ Sanofi, Astellas, Janssen. P. Barthélémy: Honoraria (self): Astellas; Advisory/Consultancy: Janssen-Cilag, Sanofi, MSD, BMS, Pfizer, Novartis, Ipsen, Roche; Travel/Accommodation/Expenses: BMS, Amgen, Pfizer, Janssen-Cilag, Roche, Ipsen. C. Helissey: Advisory/Consultancy: Sanofi, Janssen, Astellas, Roche, AstraZeneca. C. Pobel: Travel/Accommodation/Expenses: Sanofi, Ipsen, Sandoz. E. Castro Marcos: Advisory/Consultancy: AstraZeneca, Bayer, Janssen; Speaker Bureau/Expert testimony: Astellas, AstraZeneca, Bayer, Janssen, Pfizer; Research grant/Funding (institution): AstraZeneca, Bayer, Janssen; Travel/Accommodation/Expenses: AstraZeneca, Bayer, Janssen, Roche. A. Thiery-Vuillemin: Honoraria (self): Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, Roche/Genentech, Bristol-Myers Squibb, MSD, Astellas Pharma; Advisory/Consultancy: Pfizer, AstraZeneca, Sanofi, Janssen, Novartis, Ipsen, Roche, Bristol-Myers Squibb, MSD, Astellas Pharma; Research grant/Funding (institution): Pfizer; Travel/Accommodation/Expenses: Roche, MSD, Janssen, Bristol-Myers Squibb. G. Baciarello: Honoraria (self): Janssen, Roche; Advisory/Consultancy: Amgen, Astellas Oncology, Janssen, Roche; Travel/Accommodation/Expenses: Astellas Oncology, Ipsen, Janssen, Roche. E. Orillard: Honoraria (self): Astellas, Janssen; Travel/Accommodation/Expenses: Pfizer, Amgen. K. Fizazi: Honoraria (self): Astellas Pharma, Bayer, Janssen, Sanofi; Advisory/Consultancy: Amgen (Inst), Astellas Pharma, AstraZeneca (Inst), Bayer, Curevac (Inst), ESSA (Inst), Janssen Oncology, Orion Pharma GmbH, Sanofi; Travel/Accommodation/Expenses: Amgen, Janssen. All other authors have declared no conflicts of interest.

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