Phase II study of weekly cabazitaxel for ‘unfit’ metastatic castration resistant prostate cancer patients (mCRPC) progressing after docetaxel (D) treatment. Circulating tumour cell (CTC) analysis (SOGUG-CABASEM Trial)

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.