PracticeUpdate: Haematology & Oncology

PROSTATE 25

Improved survival benefit with increased docetaxel cycles in prostate cancer JAMA Oncology Take-home message

chemotherapy contributes to the survival benefit. Prospective validation is warranted. Association of survival benefit with docetaxel in prostate cancer and total number of cycles administered: a post hoc analysis of themainsail study. JAMA Oncol 2017 Jan 01;3(1)68-75, ES de Morrée, NJ Vogelzang, DP Petrylak, et al EDITOR’S NOTE By Brian E Lewis MD, MPH T he MAINSAIL study was a phase III trial of 1059 men with mCRPC who were randomised to either docetaxel + prednisone + lenalidomide or to docetaxel + prednisone + placebo. This trial demonstrated inferiority for overall survival in the lenalidomide arm. This paper is a post hoc analysis evaluating the number of cycles of docetaxel adminis- tered and survival. The authors found that the number of cycles of docetaxel admin- istered, specifically less than eight or eight or more cycles, was associated with over- all survival independent of lenalidomide use, with a hazard ratio of 1.9. Other factors that were associated in the multi- variate analysis included baseline LDH, baseline haemoglobin, baseline albumin, and baseline ECOG performance status. I think this study is an interesting analysis, but it is not terribly surprising. It seems reasonable to think that patients who are able to stay on treatment and get more therapy will do better than those patients who are not able to continue treatment. Figure 2 is interesting. This is an analy- sis of patients who received at least five cycles of docetaxel and didn’t progress stratified by number of cycles of chemo- therapy. This tells us that, if you have a patient who receives only 7 cycles of docetaxel, he has a median survival of less than 2 years, whereas if your patient gets 10 or more cycles, his median survival is closer to 3 years. This gives us some ability to predict how our patients will do from a large and relatively contemporary trial. And this prediction comes from the number of cycles of chemotherapy that the patient was able to receive.

• This study included 1059 patients with metastatic castration-resistant prostate cancer (mCPRC) from the MAINSAIL trial and evaluated the relationship between number of docetaxel cycles and overall survival. Regardless of lenalidomide treatment, receiving eight or more docetaxel cycles was associated with significantly increased overall survival. • The study results indicate that continuing docetaxel chemotherapy improves clinical benefit in patients with mCPRC, but further prospective studies are needed to validate these findings. Abstract

benefit on Mainsail was an independent prognostic factor for OS. We conducted primary univariate and multivariate analyses for the intention-to-treat population. Additional sensitivity analyses were done, excluding patients who stopped treatment for reasons of disease progression and those who received 4 or fewer cycles of docetaxel for other reasons, minimizing the effect of confounding factors. MAIN OUTCOMES AND MEASURES Total number of docetaxel cycles delivered as an independent factor for OS. RESULTS Overall, all 1059 patients from the Mainsail trial were included (mean [SD] age, 68.7 [7.89] years). Treatment with 8 or more cycles of docetaxel was associated with superior OS (hazard ratio [HR], 1.909; 95% CI, 1.660–2.194; P<0.001), irrespective of lenalidomide treatment (HR, 1.060; 95%CI, 0.924–1.215; P=0.41). Likewise, in the sensitivity analysis, patients who received a greater number of docetaxel cycles had superior OS; patients who received more than 10 cycles had a median OS of 33.0 months compared with 26.9 months in patients treated with 8 to 10 cycles; and patients who received 5 to 7 cycles had a median OS of 22.8 months (P<0.001). CONCLUSIONS AND RELEVANCE These findings suggest that continuation of docetaxel

IMPORTANCE The optimal total number of docetaxel cycles in patients with metastatic castration resistant prostate cancer (mCPRC) has not been investigated yet. It is unknown whether it is beneficial for patients to continue treatment upon 6 cycles. OBJECTIVE To investigate whether the number of docetaxel cycles administered to patients deriving clinical benefit was an independent prognostic factor for overall survival (OS) in a post hoc analysis of the MAINSAIL trial. DESIGN, SETTING, AND PARTICIPANTS TheMAINSAIL trial was a multinational randomized phase 3 study of 1059 patients with mCRPC receiving docetaxel, prednisone, and lenalidomide (DPL) or docetaxel, prednisone, and a placebo (DP). Study patients were treated until progressive disease or unacceptable adverse effects occurred. Median OS was found to be inferior in the DPL arm compared with the DP arm. As a result of increased toxic effects with the DPL combination, patients on DPL received fewer docetaxel cycles (median, 6) vs 8 cycles in the control group. As the dose intensity was comparable in both treatment arms, we investigated whether the number of docetaxel cycles administered to patients deriving clinical

Dr Lewis is Assistant Professor of Clinical

Medicine in the Department of Hematology and Medical Oncology at Tulane University School of Medicine in New Orleans.

VOL. 2 • NO. 2 • 2017