Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer
Introduction
Over the last 10 years or so, major advances have been made in the treatment of metastatic castration-resistant prostate cancer (mCRPC) [1]. Cabazitaxel is a newly available taxane which has shown survival benefit in mCRPC patients progressing during or after docetaxel therapy [2], [3], [4], [5], [6]. As for any other drug, clinicians need to learn to use the drug properly to optimise patient outcomes. A specific issue that needs to be addressed with taxanes is the early PSA flare. This is an isolated PSA rise that occurs after initiation of taxane therapy. It is uncertain whether it should lead to treatment discontinuation or not.
An early PSA flare (aka ‘PSA surge’) followed by a decrease in PSA was first reported in 2004 [7] and has been documented in up to 20% of mCRPC patients treated with first-line docetaxel chemotherapy but its impact on treatment outcome and patient management is unclear. Four retrospective studies have concluded that such a flare is not associated with adverse outcomes and can therefore be disregarded ([8], [9], [10], [11], see [12] for review). However, these studies involved small patient numbers and did not use a standard definition for the PSA flare. Any initial rise, whether relative or absolute, in PSA is considered to signal a flare. On the other hand, there is no consensus on the extent of the subsequent PSA decline for the phenomenon to be a flare. It may be a ⩾50% decline of the peak or baseline PSA value, a stable PSA of no given threshold, or even an undefined PSA response [8], [9], [10], [11]. In addition, available studies do not indicate clearly whether the observed lack of impact of the flare on treatment outcomes applies to just docetaxel, to just first-line taxane chemotherapy, or can be generalised to various chemotherapy regimens.
The aim of our study was to establish the incidence and characteristics of the PSA flare in mCRPC patients treated with second-line cabazitaxel after progression during or after docetaxel therapy. We used different definitions of PSA flare to assess the impact of flare on overall survival (OS) and on clinical or radiological progression-free survival (PFS). The underlying purpose was to determine whether the flare should or should not prompt treatment discontinuation in clinical practice.
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Patients and methods
Data on consecutive mCRPC patients treated with cabazitaxel for progression during or after docetaxel were collected retrospectively in nine centres (eight in France and one in Turkey) using an electronic case report form. Patients had received cabazitaxel between January 2007 and May 2012 either in the TROPIC phase III trial (NCT00417079) or in the cabazitaxel compassionate use programme implemented before the availability of the drug on the market. Cabazitaxel was administered as recommended,
Population characteristics and outcomes of cabazitaxel therapy
At the time of data collection, 170 mCRPC patients had been treated with cabazitaxel in the participating centres. Twelve patients were excluded because they had received only one cycle of cabazitaxel and 33 patients because of insufficient follow-up. This left 125 patients for inclusion in the present study (46 from the TROPIC trial; 79 from the compassionate use programme). Their characteristics, including data on prior treatments, are given in Table 1. Median age at the first cycle of
Discussion
Our study analysed the early PSA flare occurring on second-line chemotherapy of mCRPC patients with the recently available taxane, cabazitaxel. Two-thirds of the 125 patients had been treated outside a clinical trial in a real-life setting. The incidence of a PSA flare ranged from 8.3% to 30.6% depending upon the definition used for flare and was roughly similar to that recorded for first-line docetaxel chemotherapy (11–18%) [8], [9], [10], [11]. The time to peak of the cabazitaxel-induced PSA
Conclusions
In conclusion, the initial PSA flare during second-line cabazitaxel therapy was not associated with a worse outcome if followed by a PSA decrease of ⩾30% or ⩾50% from baseline. This finding provides additional support to the PCWG2 recommendation that an early PSA rise (prior to 12 weeks) on administration of a cytotoxic agent should be ignored in evaluating PSA response and should not be interpreted by clinicians as immediate disease progression necessitating treatment discontinuation [13].
Conflict of interest statement
AA: Honoraria: Entity: Sanofi-Aventis, Relationship: Myself.
AF: Honoraria: Entity: Sanofi-Aventis, Astellas, Janssen, Ferring, Relationship: Myself.
MO: Consultant or Advisory Role, Entity: Sanofi-Aventis, Janssen, Astellas, Relationship: Myself, Compensation: Compensated.
FM: Consultant or Advisory Role, Entity: Sanofi-Aventis, GlaxoSmithKline, Bristol Myers Squibb, Celgene, Boston Scientific, Relationship: Myself, Compensation: Compensated.
GG: Consultant or Advisory Role, Entity:
Acknowledgements
Guillaume Moriceau, resident oncologist in Saint-Etienne, and all staff who helped collect data in the participating centers.
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