Neutropenia grade ≥ 3 during treatment with docetaxel (DOC) is associated with an improved overall survival (OS): A retrospective analysis of the TAX327 phase III trial

Background

We previously showed that mCRPC patients developing grade ≥3 neutropenia (NP) with cabazitaxel had a prolonged progression-free survival (PFS) and OS (Meisel EJC 2016; 56:93-100). A risk model combining the neutrophil-to-lymphocyte ratio (NLR) and grade ≥ 3 NP was built to distinguish patients with a poor, intermediate and good prognosis.

Methods

The prospective phase III trial TAX327 randomly assigned (1:1:1) chemonaïve mCRPC patients to DOC (30 mg/m² for 5/6 weeks), DOC (75 mg/m² every 3 weeks) or mitoxantrone 12 mg/m² +prednisone 5 mg twice daily. Hematology was collected before each cycle. Prophylactic G-CSF was allowed in case of febrile neutropenia. This post-hoc analysis evaluates the influence of grade ≥ 3 NP and NLR on OS.

Results

OS in the DOC arms was significantly associated with the frequency of grade ³ 3 NP (HR 0.89 [95% CI: 0.81 – 0.98], p = 0.02). There was an even stronger association (HR 0.82 [95% CI: 0.71 – 0.94], p = 0.005), when patients with at least one episode of grade ³ 3 NP were analysed. Therefore we compared the OS of patients with multiple episodes of grade ≥3 NP to those with ≤ 1 episode of grade ≥3 NP and found a significantly prolonged OS for patients with multiple grade ≥3 NP episodes (HR 0.61 [95% CI: 0.39 – 0.97], p = 0.038). The median OS was 17.1 months for patients with a single episode of grade ≥3 NP, 18.2 months for those without grade ≥3 NP and 22.8 months for those with multiple episodes of grade ≥3 NP. The same association could be shown, when only the subgroup of patients treated with 3-weekly DOC, todays standard first line chemotherapy, was considered (HR 0.61 [95% CI: 0.38 – 0.96], p = 0.033). The biparametric risk model was applicable for mCRPC patients treated with 1^st-line chemotherapy with DOC. The HR between risk category 0 (low NLR

Conclusions

This post-hoc analysis of TAX327 phase III trial suggests that the consecutive occurrence of grade ≥ 3 neutropenia with DOC is associated with an improved OS. Combining NLR and the occurrence of grade ≥ 3 neutropenia during taxane therapy may be useful to predict outcome.

Clinical trial identification

Legal entity responsible for the study

Alexander Meisel & Frank Stenner

Funding

Sanofi

Disclosure

A. Meisel: Received Travel grants, advisory boards and honoraria from Sanofi.

R. de Wit, J.S. de Bono, O. Sartor, M. Eisenberger: Advisory boards for Sanofi. Investigator.

F. Stenner-Liewen: Received Travel grants, advisory boards and honoraria from Sanofi. Corporate sponsored research.

All other authors have declared no conflicts of interest.