Dataset Information

Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

ABSTRACT:

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/m² 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.

SUBMITTER: Madan RA

PROVIDER: S-EPMC8265825 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

Madan Ravi A RA Karzai Fatima H FH Al Harthy Munjid M Petrylak Daniel P DP Kim Joseph W JW Arlen Philip M PM Rosner Inger I Theoret Marc R MR Cordes Lisa L Bilusic Marijo M Peer Cody J CJ Dawson Nancy A NA Couvillon Anna A Hankin Amy A Williams Moniquea M Chun Guin G Owens Helen H Marte Jennifer L JL Lee Min-Jung MJ Tomita Yusuke Y Yuno Akira A Trepel Jane B JB Lee Sunmin S Steinberg Seth M SM Gulley James L JL Figg William D WD Dahut William L WL

BJU international 20201023 4

<h4>Objective</h4>To evaluate the safety and efficacy of cabozantinib combined with docetaxel.<h4>Patients and methods</h4>This was a phase 1/2 multicentre study in patients with metastatic castration-resistant prostate cancer (mCRPC). Docetaxel (75 mg/m<sup>2</sup> 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 wi ...[more]

PMID: 32969563

Similar Datasets

Project description:BackgroundBone metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) are associated with debilitating pain and functional compromise.ObjectiveTo compare pain palliation as the primary endpoint for cabozantinib versus mitoxantrone-prednisone in men with mCRPC and symptomatic bone metastases using patient-reported outcome measures.Design, setting, and participantsA randomized, double-blind phase 3 trial (COMET-2; NCT01522443) in men with mCRPC and narcotic-dependent pain from bone metastases who had progressed after treatment with docetaxel and either abiraterone or enzalutamide.InterventionCabozantinib 60mg once daily orally versus mitoxantrone 12mg/m2 every 3wk plus prednisone 5mg twice daily orally.Outcome measurements and statistical analysisThe primary endpoint was pain response at week 6 confirmed at week 12 (≥30% decrease from baseline in patient-reported average daily worst pain score via the Brief Pain Inventory without increased narcotic use). The planned sample size was 246 to achieve ≥90% power.Results and limitationsEnrollment was terminated early because cabozantinib did not demonstrate a survival benefit in the companion COMET-1 trial. At study closure, 119 participants were randomized (cabozantinib: N=61; mitoxantrone-prednisone: N=58). Complete pain and narcotic use data were available at baseline, week 6, and week 12 for 73/106 (69%) patients. There was no significant difference in the pain response with cabozantinib versus mitoxantrone-prednisone: the proportions of responders were 15% versus 17%, a -2% difference (95% confidence interval: -16% to 11%, p=0.8). Barriers to accrual included pretreatment requirements for a washout period of prior anticancer therapy and a narcotic optimization period to maximize analgesic dosing.ConclusionsCabozantinib treatment did not demonstrate better pain palliation than mitoxantrone-prednisone in heavily pretreated patients with mCRPC and symptomatic bone metastases. Future pain-palliation trials should incorporate briefer timelines from enrollment to treatment initiation.Patient summaryCabozantinib was not better than mitoxantrone-prednisone for pain relief in patients with castration-resistant prostate cancer and debilitating pain from bone metastases.

Dataset Information

Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

Objective

Patients and methods

Results

Conclusion

Publications

Cabozantinib plus docetaxel and prednisone in metastatic castration-resistant prostate cancer.

Similar Datasets

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