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CHICAGO -- Overall survival in metastatic prostate cancer improved by more than a year when patients received docetaxel at the start of androgen deprivation therapy (ADT), according to trial results that oncologists here called "unprecedented."

Men randomized to ADT plus docetaxel had a median overall survival (OS) of 57.6 months versus 44.0 months for men who received ADT alone. The survival benefit appeared to be driven by the activity of the combination in patients with a high volume of disease, who had a 40% reduction in the survival hazard, reported , of the Dana-Farber Cancer Institute in Boston, and colleagues at the American Society of Clinical Oncology annual meeting.

Prostate-specific antigen (PSA) response, time to castration resistance, and time to progression differed significantly in favor of the ADT-docetaxel arm, they said.

"This is one of the biggest improvements in survival we have seen in a trial involving patients with an adult metastatic solid tumor," Sweeney said.

The study outcome could prove to be a "real game changer, because the differences are real," said Derek Raghavan, MD, PhD, of Carolinas Healthcare System's Levine Cancer Center in Charlotte, N.C.

"You don't need a clever statistician to identify differences when you see a difference of a year in median survival. That's a very big deal," Raghavan told 番茄社区.

Nicholas Vogelzang, MD, of Comprehensive Cancer Centers of Nevada in Las Vegas, said the results could be the biggest development in the management of advanced prostate cancer since surgical orchiectomy.

"Dr. Huggins showed in 1940 that surgical castration -- removal of the gonads -- would make prostate cancer go away," Vogelzang said. "Seventy-five years later, we now have something that truly adds to that advance. Men don't have to have their gonads cut off; they don't have to take [leuprolide] alone... they still have to [receive ADT], but we extend life more by giving the chemotherapy with it. That's a pretty big deal."

Sweeney reported the results of the CHAARTED trial to address the question of whether adding chemotherapy to ADT would prolong survival for men with metastatic prostate cancer compared with ADT alone.

Chemical or medical castration with testosterone-suppressing drugs has been a mainstay of therapy for metastatic prostate cancer. Over time, however, the disease acquires resistance to testosterone suppression, and standard clinical practice has been to initiate chemotherapy at progression to resistance.

Whether giving chemotherapy upfront with ADT could prolong the hormone-sensitive interval remained unclear. CHAARTED was designed to eliminate the ambiguity.

Investigators randomized 790 men with newly diagnosed hormone-sensitive metastatic prostate cancer and randomized them to standard ADT or to ADT plus docetaxel. OS was the primary endpoint.

The trial ended prematurely after an interim analysis showed a statistically significant survival difference between treatment groups. After a median follow-up of 29 months, 136 patients in the ADT arm had died as compared with 101 in the group that received ADT and chemotherapy.

The 13-month difference in median OS translated into a 39% reduction in the survival hazard (HR 0.61, 95% CI 0.47-0.80, P=0.0003). An even larger survival difference existed among men who had a high disease burden at enrollment. The combination therapy resulted in a median OS of 49.2 months versus 32.2 months for ADT alone (HR 0.60, 95% CI 0.45-0.81, P=0.0004).

Other key disease-related outcomes also favored the docetaxel arm:

• PSA <0.2 ng/dL at 6 months: 27.5% versus 14.0% (P<0.0001)
• PSA <0.2 ng/dL at 12 months: 22.7% versus 11.7% (P<0.0001)
• Median time to castration resistance: 20.7 versus 14.7 months (P<0.0001)
• Median time to clinical progression: 32.7 versus 19.8 months (P<0.0001)

Press briefing moderator and ASCO president , added to the study's accolades.

"In prostate cancer, I'm not aware of any historical study that ever offered up this magnitude of improvement in survival," said Hudis, of Memorial Sloan-Kettering Cancer Center in New York City. "Quite frankly, across all of the solid tumors, this is an almost unprecedented improvement in median survival."

Using a baseball analogy, Raghavan likened the result to a home run.

"My own view is that if you can show this to a man on the street and ask 'Is this worthwhile?' and the man on the street says 'Yeah, that's a big difference,' then you've got a home run," Raghavan said.

The CHAARTED results could be just the first of many home runs in prostate cancer, given the large number of new drugs for treating the disease, each of which could be evaluated in various combinations or sequences with ADT.

"At the end of the day, we have more arrows in our quiver, and we've got the docetaxel arrow out first," Sweeney told 番茄社区. "Men are living longer without their symptoms, and I hope they will be able to reap the potential of these new drugs."

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