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Abstract
IntroductionCabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration‐resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges.Patients and methodsWe retrospectively identified 22 mCRPC patients previously treated with docetaxel and/or androgen receptor‐targeted agents who received multiple cabazitaxel rechallenges in 9 French centers. Cabazitaxel was initiated at a dose of 25 mg/m2 q3week. A reduced dose (20 mg/m2 q3w) or an alternative schedule (mainly 16 mg/m2 q2w) was increasingly used for subsequent rechallenges. Progression‐free survival, prostate‐specific antigen (PSA) response, best clinical response, and grade ≥3 toxicities were collected. Overall survival was calculated from various time points.ResultsTwenty‐two patients with an initial response to cabazitaxel were rechallenged at least twice. The median number of cabazitaxel cycles was 7 at first cabazitaxel treatment, 6 at first rechallenge, and 5 at subsequent rechallenges. Median progression‐free survival at first rechallenge was 9.6 months and 5.6 months at second rechallenge. Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life‐extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. There was no cumulative grade ≥3 neuropathy or nail disorder and one case of febrile neutropenia.ConclusionCabazitaxel multiple rechallenges may be a treatment option without cumulative toxicity in heavily pretreated patients having a good response to first cabazitaxel use and still fit to receive it.Novelty & Impact StatementsPatients with metastatic castration‐resistant prostate cancer can be treated with Cabazitaxel after docetaxel and androgen receptor‐targeted agent. This chemotherapy can be used multiple times with efficacy and manageable toxicity.
Highlights
Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration-resistant prostate cancer who had a good initial response to cabazitaxel and who are still fit to receive it
Cabazitaxel use is restricted to patients previously treated with docetaxel,[3,4] olaparib use is restricted to patients with BRCA1/2 mutations previously treated with an androgen receptor-targeted agent (ARTA)[2] and there is level 1 evidence that patients who have progressed with a first ARTA poorly respond to another ARTA.[2,5,6]
We retrospectively reviewed clinical data of 710 consecu- Median follow-up from metastatic castration-resistant prostate cancer (mCRPC) diagnosis for the tive mCRPC patients treated with cabazitaxel in nine 22 mCRPC patients rechallenged with cabazitaxel was
Summary
Since 2004, several agents have shown an overall survival (OS) benefit in metastatic castration-resistant prostate cancer (mCRPC) patients, including in chronological order docetaxel, sipuleucel-T cabazitaxel, abiraterone acetate, enzalutamide, radium- 223, and olaparib.[1,2] Cabazitaxel use is restricted to patients previously treated with docetaxel,[3,4] olaparib use is restricted to patients with BRCA1/2 mutations previously treated with an androgen receptor-targeted agent (ARTA)[2] and there is level 1 evidence that patients who have progressed with a first ARTA poorly respond to another ARTA.[2,5,6] Treatment options in mCRPC are limited. Patients rechallenged with cabazitaxel were good responders to first cabazitaxel use, in terms of PSA response, clinical benefit, and PFS (Table 2). Overall patients received a median number of 19.5 cabazitaxel cycles (7 at first use, 6 at first rechallenge, and 5 at subsequent rechallenges). The median number of cycles received was 7 (4 to 12), 6 (3 to 16), 5 (1 to 12), 5 (3 to 12), and 5 at first, second, third, fourth, and fifth use of cabazitaxel, respectively. Total number of patients Median age at first treatment initiation (range), years Gleason score 8–10 at diagnosis, n (%) Median follow-up from mCRPC diagnosis, months Characteristics at cabazitaxel initiation Metastatic sites (Halabi classification), n (%).
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