BETHESDA, MD USA (UroToday.com) - CHAARTED is a phase III, double-arm, randomized trial that looked at whether the addition of upfront chemotherapy to hormonal therapy improved overall survival in patients with hormone-sensitive metastatic cancer. Conventionally, chemotherapy is given when patients develop castrate-resistant metastatic prostate cancer.
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Seven hundred ninety patients were enrolled in the trial between July 2006 to November 2012 and randomized in 1:1 fashion (393 men in ADT alone arm and 397 men in ADT + docetaxel arm). Patients are stratified by high-volume (visceral metastasis and/or presence of 4 or more bone lesions) vs low-volume, age, ECOG status, and prior hormonal therapy use.
It was found that androgen deprivation therapy plus docetaxel resulted in a median survival of 57.6 months compared with 44 months in the androgen deprivation therapy alone arm (HR = 0.61, p = 0.0003). The benefit of docetaxel therapy was found to be more evident in the high-volume metastatic group. In patients with high-volume metastatic disease, there is a 17-month improvement in median OS, which is the largest found in any other chemotherapy trials. In the low-volume metastatic disease group, median overall survival was not reached. About 87% of patients were able to complete all cycles of chemotherapy. Additionally, addition of chemotherapy benefited all secondary end points—almost twice as many patients had an undetectable PSA and chemo also doubled the median time to developing castrate resistant prostate cancer.
Dr. Aragon-Ching then discussed a French study, GETUG 15, which did not show OS benefit with addition of chemotherapy in hormone sensitive metastatic cancer. Only 22% of all patients in GETUG 15 were high risk rather than 66% in the CHAARTED trial.
Should early chemotherapy along with ADT be standard of care? This depends on patients’ clinical and biological processes. The clinician needs to assess whether comorbidities are present such that early chemotherapy would not compromise survival due to toxic deaths. Second, this depends on biological processes, which still need to be elucidated. Knowledge of upfront resistance to androgen-signaling targeted agents and taxane-inhibition of androgen-receptor signaling may push us towards earlier chemotherapy use.
She concluded by saying the real impact that the CHAARTED trial has on clinical practice is that it illustrates earlier referral to a medical oncologist for chemotherapy needs to be considered.
While the results of the CHAARTED trial are exciting, it remains to be seen how this will change clinical practice.
Jeanny Aragon-Ching, MD, FACP
George Washington University Medical Center Medical Faculty Associates, Washington, DC USA
Mohammed Haseebuddin, MD* from the 2014 Winter Meeting of the Society of Urologic Oncology (SUO) "Defining Excellence in Urologic Oncology" - December 3 - 5, 2014 - Bethesda, MD USA
*Fox Chase Cancer Center, Philadelphia, PA USA