Formal discussant of the E3805 study, Michael J. Morris, MD, Associate Member at Memorial Sloan Kettering Cancer Center in New York, said that these results confirm the role of upfront chemotherapy along with androgen-deprivation therapy in men with newly diagnosed metastatic hormone-sensitive prostate cancer who have high-volume disease.

“The investigators have adequately shown that upfront docetaxel confers a survival advantage for patients with high-volume newly diagnosed metastatic disease. However, there are insufficient data at this time to recommend that low-volume patients with metastatic hormone-sensitive prostate cancer undergo chemotherapy,” Dr. Morris told listeners.

Study Implications

The original survival benefits reported with docetaxel in metastatic castration-resistant prostate cancer were modest—about 2 to 3 months absolute improvement with a 20% to 25% reduction in death. “Today, we are moving docetaxel forward from the castration-resistant state to the castration-sensitive state. The survival benefits of docetaxel are amplified in this setting, with a 40% reduction in risk of death and prolonged time to radiographic progression and the castration-resistant state,” he said.

“The study results bear on the ongoing dialog about cost vs value in cancer care. Docetaxel is going to cost less than our newer therapies. I estimate that using docetaxel in castration-resistant prostate cancer gains 81 days of life for $15,000 of drug costs at wholesale  prices. If docetaxel is applied in castration-sensitive disease, it gains 476 days of life at a cost of $9,000 for six cycles,” Dr. Morris said.

How do the results apply to clinical practice? Dr. Morris said that oncologists need to avoid misapprehension of true risk, which leads to a misapplication of therapy. “We need to be able to identify the appropriate high-volume patients who need chemotherapy and low-volume patients who should not get chemotherapy at this juncture,” he continued.

The definition used in the study for high-volume disease was four or more bone metastases and one or more lesions in any bony structure beyond the spine/pelvis or visceral disease. Dr. Morris said a more precise definition of extensive disease is needed to identify which patients can benefit from early chemotherapy. A more refined definition should be based on disease distribution and volume. Four lesions could reflect low or high disease burden depending on where they are and how much area they affect.

Federal Funding

Dr. Morris emphasized that the study was sponsored by National Institutes of Health. “This difficult and long study has changed the standard of care for some patients in the face of ever-diminishing resources,” he noted.

In fact, all four of ASCO’s Plenary Session studies were federally funded. In 2009, approximately 500 abstracts submitted to ASCO were federally funded, compared to 169 in 2014—indeed, shrinking resources. ■

Disclosure: Dr. Morris reported no potential conflicts of interest.