Docetaxel Adds To Overall Survival in Metastatic Castration-Resistant Prostate Cancer

MedicalResearch.com Interview with:
Prof. Ronald de Wit, MD, PhD
Medical Oncologist
Medical Oncology
Erasmus MC
University Medical Center, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mainsail is one of the largest phase 3 trials in the setting of  Metastatic Castration-Resistant Prostate Cancer (mCRPC)  in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We found that the total number of docetaxel cycles delivered was an independent and important contributor to the overall survival benefit provided by docetaxel chemotherapy, that was independent of known prognostic factors for survival. Treatment with ≥8 cycles of docetaxel was associated with superior OS (P<0.0001), irrespective of lenalidomide treatment (p=0.3608). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received ˃10 cycles had a median OS of 33.0 months compared to 26.9 months in patients treated with 8-10 cycles and 22.8 months for patients treated with 5-7 cycles of docetaxel (P<0.0001).. Patients in the Mainsail study had been treated according to a strict protocol, mandating continuation of the allocated treatment until documented disease progression, or until unacceptable adverse effects occurred.

In the sensitivity analysis we corrected for confounding factors, including disease progression as the reason for stopping docetaxel. The main reason for stopping protocol treatment early, though, was adverse effects. Enhanced toxicity by the addition of lenalidomide to docetaxel in the experimental arm resulted in a lower cumulative dose of docetaxel, reflected by fewer docetaxel cycles administered and some more frequent dose reductions. Our data strongly suggest that the difference in the cumulative docetaxel exposure caused the worse OS in the experimental arm. These findings imply that the total dose of docetaxel, as reflected in total the number of cycles achieved, contributes to the eventual survival gain by chemotherapy in the mCRPC patient population.

MedicalResearch.com: What should readers take away from this report?

Response: These findings imply that the total dose of docetaxel, as reflected in total the number of cycles achieved, contributes to the eventual survival gain by chemotherapy in the Metastatic Castration-Resistant Prostate Cancer patient population.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: A prospective study, either in mCRPC, or potentially in the setting of mHSPC, may lend further prospective evidence.

Citation:

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