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Sailing into “UnCHAARTED” waters




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Chemotherapy comes alive for prostate cancer!

staff-chowdhury1Systemic therapy for metastatic prostate cancer has radically changed in the last 10 years with the introduction of several novel agents that have shown significant improvements in progression free and overall survival. These have all been studied in metastatic castrate refractory prostate cancer (mCRPC) and have improved overall survival but in each case by less than 6 months. (The latest major breakthrough is the introduction of a relatively old drug, docetaxel chemotherapy, earlier in the disease for hormone sensitive patients).

In this week’s New England Journal of Medicine we see the eagerly awaited results from the CHAARTED study from Christopher Sweeney and colleagues. This novel study aimed to improve treatment for men with newly diagnosed hormone sensitive metastatic prostate cancer by adding docetaxel chemotherapy to androgen deprivation therapy (ADT).

790 men with newly diagnosed metastatic prostate cancer were randomised to ADT plus docetaxel (6 cycles at 75mg/m2) or ADT alone. The addition of docetaxel to ADT was shown to significantly improve overall survival by 13.6 months (57.6 months vs. 44.0 months; p<0.001). The clinical benefit was greatest in the subgroup with high volume disease where the improvement in overall survival was 17 months (49.2 months versus 32.2 months). High volume disease was defined as the presence of visceral metastases and/or 4 or more bone metastases with at least one beyond the vertebral bodies or pelvis. The combination was well tolerated with approximately 6% of patients having neutropenic fever and one death possibly related to docetaxel.

The results from this study are truly practice changing. Supporting evidence from the UK STAMPEDE study (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) was presented at this year’s American Society of Clinical Oncology (ASCO) meeting. STAMPEDE showed that for men with metastatic hormone sensitive prostate cancer 6 cycles of docetaxel in addition to ADT improved median overall survival by 22 months (43 versus 65 months).

Chemotherapy for metastatic prostate cancer has had a checkered past with a lack of enthusiasm and nihilism from clinicians and patients. The results from CHAARTED and STAMPEDE are already changing those views. The prostate cancer community needs to react to these results and look to make this treatment available to all suitable men. There are issues with regards to costs of chemotherapy (although docetaxel is now generic), workload, sequence, patient selection, toxicity management, etc. The CHAARTED and STAMPEDE investigators must also use this opportunity to interrogate the tumour samples from these studies to see if they can identify biomarkers that predict docetaxel activity. We will not get this opportunity again as docetaxel + ADT will be be standard of care for future studies.

The clinical benefit from the addition of docetaxel to ADT is one of the largest seen in any oncology study. All men presenting with newly diagnosed metastatic prostate cancer should be considered for 6 cycles of docetaxel in addition to ADT.

 

Simon Chowdhury is a Consultant Medical Oncologist at Guy’s, King’s and St Thomas’ Hospitals, London. He is actively involved in clinical trial research into urological cancers.

 

 

  1. Declan Murphy
    Totally agree Simon. This paper will mark one of the biggest changes in management of advanced prostate cancer in history. I suspect that longer follow-up of CHAARTED and forthcoming STAMPEDE papers will lead to us using the combination regimen for men with lower volume metastases also. Medical oncologists will be busy!
  2. Prokar Dasgupta
    Noel Clarke delivered the same message at BAUS from STAMPEDE.
    Q = Will governments fund it?
  3. Vincenzo Ficarra
    CHAARTED trial is really a landmark study supporting the immediate use of Docetaxel plus ADT in metastatic prostate Cancer. This new paradigm can change drammatically the current standard practice. My questions are 1. Are we (urologists and oncologists) already ? 2. Is economical feasible? 3. Which will be' the role of other "new drugs" in this new scenario ? 4. Is Docetaxel + ADT for all cases ? Probably the results of CHAARTED trial should be' analyzed and interpretated with more caution and above all considering the different World context
  4. Simon Chowdhury
    Thanks Declan and Prokar. The STAMPEDE results show that for all metastatic patients there is a significant overall survival benefit and so I believe all metastatic patients should be offered docetaxel. STAMPEDE also included men with high risk localised disease. There was a benefit in progression free survival but as yet no survival benefit. What should we offering these patients?

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