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Cabozantinib plus docetaxel and prednisone in metastatic castration‐resistant prostate cancer
Author(s) -
Madan Ravi A.,
Karzai Fatima H.,
Al Harthy Munjid,
Petrylak Daniel P.,
Kim Joseph W.,
Arlen Philip M.,
Rosner Inger,
Theoret Marc R.,
Cordes Lisa,
Bilusic Marijo,
Peer Cody J.,
Dawson Nancy A.,
Couvillon Anna,
Hankin Amy,
Williams Moniquea,
Chun Guin,
Owens Helen,
Marte Jennifer L.,
Lee MinJung,
Tomita Yusuke,
Yuno Akira,
Trepel Jane B.,
Lee Sunmin,
Steinberg Seth M.,
Gulley James L.,
Figg William D.,
Dahut William L.
Publication year - 2021
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.15227
Subject(s) - docetaxel , cabozantinib , medicine , prostate cancer , prednisone , oncology , castration , abiraterone , cabazitaxel , urology , cancer , hormone , androgen deprivation therapy , androgen receptor
Objective To evaluate the safety and efficacy of cabozantinib combined with docetaxel. Patients and Methods This was a phase 1/2 multicentre study in patients with metastatic castration‐resistant prostate cancer (mCRPC). Docetaxel (75 mg/m 2 every 3 weeks with daily prednisone 10 mg) was combined with escalating doses of daily cabozantinib (20, 40 and 60 mg). Based on the results of the phase 1 study, the investigation was expanded into a randomized study of docetaxel with prednisone (hereafter 'docetaxel/prednisone') plus the maximum tolerated dose (MTD) of cabozantinib compared with docetaxel/prednisone alone. Results A total of 44 men with mCRPC were enrolled in this phase 1/2 trial. An MTD of 40 mg cabozantinib plus docetaxel/prednisone was determined. Dose‐limiting toxicities were neutropenic fever and palmar‐plantar erythrodysesthesia, and there was one death attributable to a thromboembolic event. In addition, grade 3 or 4 myelosuppression, hypophosphataemia and neuropathy were seen in three or more patients. In the phase 1 study, the median time to progression (TTP) and overall survival (OS) time were 13.6 and 16.3 months, respectively. In the phase 2 study, which was terminated early because of poor accrual, the median TTP and OS favoured the combination ( n = 13) compared to docetaxel/prednisone alone ( n = 12; 21.0 vs 6.6 months; P = 0.035 and 23.8 vs 15.6 months; P = 0.072, respectively). Conclusion Despite the limited number of patients in this study, preliminary data suggest that cabozantinib can be safely added to docetaxel/prednisone with possible enhanced efficacy.