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Hormonal therapies combined with chemotherapy significantly improved radiographic progression-free survival (rPFS) for men with de novo metastatic castration-sensitive prostate cancer (mCSPC), results from a phase III study showed.

In the , the triplet therapy of abiraterone (Zytiga) plus androgen-deprivation therapy (ADT) and docetaxel extended rPFS by a median 2.5 years for these patients, and could be practice changing, reported Karim Fizazi, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

"Regardless of overall survival [OS] results, this data question whether we should deny patients approximately 2 and a half years without radiographic progression or death, or whether combining ADT/docetaxel and abiraterone/prednisone should simply become the new standard of care," Fizazi said during a presentation at the virtual .

He noted that the standard of care for mCSPC has rapidly evolved over the last several years. For example, when the PEACE-1 trial began accruing patients in 2013, ADT alone was the standard of care (SOC). But in the time since, the trend has been to combine ADT with docetaxel, novel hormone therapies, or radiotherapy to the primary tumor (for patients with low tumor burden), an approach that has increased survival and become the new standard.

The PEACE-1 trial included 1,173 patients with de novo mCSPC who received up to 3 months of ADT before randomization. These patients were randomized to receive SOC therapy alone, SOC and abiraterone plus prednisone, SOC plus radiotherapy to the prostrate, or SOC and abiraterone plus radiotherapy.

Due to the changing SOC during the accrual period of the trial, treatment was amended at several points. In 2015, it was changed to allow for docetaxel use according to the investigator's decision and patient's willingness to receive chemotherapy. And with the publication of the trial (which Fizazi led) and , the protocol for PEACE-1 was amended to make docetaxel mandatory as part of SOC.

No interaction was seen between use of local radiotherapy and abiraterone on rPFS, which allowed the team to pool the two abiraterone arms for analysis, he explained.

SOC was ADT plus docetaxel for 710 patients and ADT alone for 463 patients. At 42 months, rPFS for the overall trial population favored the abiraterone arm (abiraterone plus SOC of ADT with or without radiotherapy) over the SOC arm (HR 0.54, CI 95% 0.46-0.60), for a median of 4.5 years versus 2.2 years, respectively, Fizazi reported.

And when analyzing the rPFS for the ADT-plus-docetaxel SOC population of 710 patients, the researchers found that abiraterone added to SOC also favored that arm (HR 0.50, CI 95% 0.40-0.62), with a median of 4.5 years rPFS compared with 2.0 years in the SOC arm.

"That difference is highly significant," Fizazi said. "Importantly, all tested subgroups pretty much benefited from the addition of abiraterone. This was true regardless of radiotherapy use, docetaxel use, and whatever the metastatic extension and sites, including men with visceral metastases."

Abiraterone also resulted in a "very clear and significant improvement" in secondary endpoints such as castration resistance-free survival for the overall population (HR 0.40, CI 95% 0.35-0.47) and ADT-plus-docetaxel group (HR 0.38 95% CI 0.31-0.47), Fizazi said.

He noted, however, that OS results at the time of presentation of the data were still immature and not able to be reported.

As for treatment safety, "it was very reassuring to see that abiraterone, even used concurrently with docetaxel, did not increase the risk of febrile neutropenia, or other hematological toxicities related to docetaxel," he added.

The discussant for the study, Lisa Horvath, PhD, MBBS, of the Sydney Cancer Center in Australia, compared the results with those of similar studies, such as ENZAMET, where she was a co-investigator.

"ENZAMET is the closest in that both of these studies used concurrent docetaxel with either abiraterone or enzalutamide [Xtandi], and stratified the use of docetaxel," she said. "The benefits are very similar. The difference is ENZAMET has met its interim analysis for overall survival, and found no benefit in triplet therapy."

"Further follow-up from both these studies and data from the study are going to be critical to decide where this treatment falls within our standard of care," Horvath added.

When asked how the new results could change treatment, Fizazi pointed out that 10 years ago an mCSPC patient typically had a 1-year rPFS on ADT alone. That was prolonged with the addition of docetaxel to about 2 years, and now has been extended to 4.5 years with the triplet approach.

"I will be keen to see the overall survival data," he said. "But I guess that even if overall survival is similar between the two arms, and we don't have cumulative toxicities with the triplet treatment, then I think we should consider changing our standard treatment for those patients, given that 2 and a half years is just big."

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