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

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. Table: 1363MO

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.

Editorial acknowledgement

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.