Cabazitaxel vs Abiraterone or Enzalutamide in Poor-Prognosis Metastatic Castration-Resistant Prostate Cancer

[Balsam01]

TAKE-HOME MESSAGE

The authors of this multicenter, phase II trial randomized 95 men with metastatic castration-resistant prostate cancer (mCRPC) to cabazitaxel plus prednisone or physician’s choice of androgen receptor pathway inhibitor (enzalutamide or abiraterone plus prednisone). All patients were androgen receptor pathway inhibitor–naïve and had poor prognostic features. The clinical benefit rate was higher with cabazitaxel treatment (80% vs 62%). Overall survival was numerically longer (median 37 vs 15.5 months) but did not reach statistical significance.

These findings provide supporting evidence for the general clinical perspective that patients with poor prognosis mCRPC may be better treated with upfront chemotherapy. Baseline and on-treatment change in ctDNA demonstrated prognostic value.

– Paul J. Hampel, MD

Abstract

This abstract is available on the publisher's site.

PURPOSE

Treatment for poor prognosis metastatic castration-resistant prostate cancer (mCRPC) includes taxane chemotherapy and androgen receptor pathway inhibitors (ARPI). We sought to determine optimal treatment in this setting.

PATIENTS AND METHODS

This multicentre, randomised, open-label, phase 2 trial recruited patients with ARPI-naïve mCRPC and poor prognosis features (presence of liver metastases, progression to mCRPC after <12 months of androgen deprivation therapy, or ≥4 of 6 clinical criteria). Patients were randomly assigned 1:1 to receive cabazitaxel plus prednisone (Group A) or physician's choice of enzalutamide or abiraterone plus prednisone (Group B) at standard doses. Patients could cross-over at progression. The primary endpoint was clinical benefit rate for first-line treatment (defined as PSA response ≥50%, radiographic response, or stable disease ≥12 weeks).

RESULTS

95 patients were accrued (median follow-up 21.9 months). First-line clinical benefit rate was greater in Group A versus B (80% vs 62%, p=0.039). Overall survival was not different between Group A and B (median 37.0 vs 15.5 months, HR=0.58, p=0.073) nor was time to progression (median 5.3 vs 2.8 months, HR=0.87, p=0.52). The most common first-line treatment-related grade ≥3 adverse events were neutropenia (cabazitaxel 32% vs ARPI 0%), diarrhea (9% vs 0%), infection (9% vs 0%) and fatigue (7% vs 5%). Baseline circulating tumour DNA (ctDNA) fraction above the cohort median and on-treatment ctDNA increase were associated with shorter time to progression (HR = 2.38, p < 0.001; HR = 4.03, p < 0.001). Patients with >30% ctDNA fraction at baseline had markedly shorter overall survival than those with undetectable ctDNA (HR = 38.22, p < 0.001).

CONCLUSIONS

Cabazitaxel was associated with a higher clinical benefit rate in patients with ARPI-naïve poor prognosis mCRPC. CtDNA abundance was prognostic independent of clinical features, and holds promise as a stratification biomarker.

Citation: Annals of Oncology

Cabazitaxel Versus Abiraterone or Enzalutamide in Poor Prognosis Metastatic Castration-Resistant Prostate Cancer: A Multicentre, Randomised, Open-Label, Phase 2 Trial

Ann. Oncol 2021 Apr 06;[EPub Ahead of Print], M Annala, S Fu, JVW Bacon, J Sipola, N Iqbal, C Ferrario, M Ong, D Wadhwa, SJ Hotte, G Lo, B Tran, LA Wood, JR Gingerich, SA North, CJ Pezaro, JD Ruether, SS Sridhar, HML Kallio, DJ Khalaf, A Wong, K Beja, E Schönlau, S Taavitsainen, M Nykter, G Vandekerkhove, AA Azad, AW Wyatt, KN Chi

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[Schwah]

I don’t get it. “Overall survival was not different between Group A and B (median 37.0 vs 15.5 months”. How could more than a doubling of survival not be different ??

Schwah

[Balsam01 in reply to Schwah]

I think they say that the difference did not attain statistical significance probably due to the small sample sizes. But I think the difference is important despite not reaching .05.

[Spyder54]

I may soon be mCRPC. I re-read it 3x. Like Schwah, dont understand why OS, and time to progression was not different in Group A vs B?I also note Quality of Life (QOL), often not mentioned.