753P - Phase II study of weekly cabazitaxel for ‘unfit’ metastatic castration resistant prostate cancer patients (mCRPC) progressing after docetaxel (D) t...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Prostate Cancer
Presenter Urbano Anido
Citation Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372
Authors U. Anido1, M.J. Juan Fita2, L. Munielo-Romay3, B. Pérez-Valderrama4, B. Mellado5, M. Ochoa de Olza6, O. Fernandez Calvo7, D. Castellano8, E.M. Fernandez Parra9, M. Domenec10, S. Hernando11, J. Arranz Arija12, C. Caballero13, I. Duran14, M. Campayo5, M.A. Climent15
  • 1Dept. Of Medical Oncology, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, 15706 - Santiago de Compostela/ES
  • 2Medical Oncology, Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 3Traslational Medical Oncology Group, Liquid Biopsy Analysis Unit, Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, 15706 - Santiago de Compostela/ES
  • 4Medical Oncology, Hospital Universitario Virgen del Rocio, Sevilla/ES
  • 5Medical Oncology, Hospital Clinic y Provincial de Barcelona, Barcelona/ES
  • 6Medical Oncology, Vall d`Hebron University Hospital Institut d'Oncologia, 08035 - Barcelona/ES
  • 7Medical Oncology, Complejo Hospitalario De Orense, Ourense/ES
  • 8Medical Oncology, University Hospital 12 De Octubre, Madrid/ES
  • 9Medical Oncology, Hospital Virgen Valme, Sevilla/ES
  • 10Medical Oncology, Althaia, Xarxa Assistencial i Universitària de Manresa, 08243 - Manresa/ES
  • 11Medical Oncology, HUFA Hospital Universitario Fundacion Alcorcon, Alcorcon/ES
  • 12Servicio De Oncologia Medica, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 13Medical Oncology, Hospital General Universitario Valencia, Valencia/ES
  • 14Departamento De Oncologia, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 15Servicio De Oncología Médica, Instituto Valenciano de Oncología, 46009 - Valencia/ES

Abstract

Background

Cabazitaxel (C), a novel taxane developed to overcome D resistance, showed an overall survival improvement after D in mCRPC in a three-weekly schedule. Its main toxicity is hematological,. We aimed to evaluate the relation of CTC counts and its early response with efficacy of weekly C/prednisone (P) schedule in "unfit" mCRPC previously treated with D.

Methods

Unfit pts (ECOG 2, dose reduction due to febrile neutropenia during treatment with D or radiation therapy affecting more than 25% of bone marrow reserve) with mCRPC progressing after D with adequate bone marrow, liver and kidney functions were included. C 10 mg/m2 was administered on days 1, 8, 15 and 22 of 5-week cycles with daily prednisone 5 mg b.i.d. Radiological and PSA response was evaluated according to the PCCTWG II criteria. CellSearch system was used for counting the CTC. Early CTC response defined as a drop of ≥30% at 4 weeks from baseline. Toxicity was evaluated according NCI-CTC AE.

Results

70 pts have been enrolled. Median age was 73 y (range 54-85), 71% pts had ECOG 2, 84% had bone, 16% liver and 11% lung metastases. Twenty-four pts (34.3%) achieve ≥50% PSA response and 7 (10.0%) ≥80%. Radiological response (PR) was observed in 4 pt (5.7%) and SD in 32 pts (45.7%). Median PSA PFS was 4.8 months and 12 weeks PSA PFS was 68.6%. Median OS was 12.6 months. Most frequent toxicities of all grades and grade 3-4 as % of pts were: anemia (80-17%), asthenia (54-19%), thrombocytopenia (20-10%), diarrhea (36-1%), nauseas (27-1%), neutropenia (14-1%), peripheral neuropathy (19-0%), and anorexia (30-3%). Neither grade IV diarrhea nor febrile neutropenia were observed. Nineteen of 32 pts (59%) had early CTC response. Results show a favorable association between early CTC response and PSA response (77% vs 53%) (p = 0,267), clinical benefit (RP + EE) (68% vs 31%) (p = 0,070), overall survival (15.8 m vs 7.2 m) (p = 0,175) and PSA PFS (7.8 m vs 3.1 m) (p = 0,004).

Conclusions

Our results suggest that weekly C plus P in unfit pts is an effective regimen with lower toxicity than the 3-weekly standard treatment. Early CTC response seems to be related with efficacy and could be of value as early efficacy endpoint.

Clinical trial identification

NCT01518283 / EudraCT: 2011-004627-12

Legal entity responsible for the study

SOGUG (Spanish Oncology Genitourinary Group)

Funding

Sanofi

Disclosure

I. Duran: Consulting or advisory role: Amgen, Astellas, Roche-Genetech, Novartis, Janssen, Pierre-Fabre. Research funding: Sanofi, Janssen.

All other authors have declared no conflicts of interest.