Researchers tested the administration of bone-targeted agents once every 12 weeks vs once every 4 weeks for a year in patients with metastatic castration-resistant prostate cancer.
Administration of bone-targeted agents (BTAS) once every 12 weeks for a year was non-inferior to their use once every 4 weeks in patients with either metastatic castration-resistant prostate cancer (CRPC) or breast cancer, according to results of the REaCT-BTA trial.
“We know that bone is the most common site of recurrence in patients with prostate and breast cancer,” said Mark J. Clemons, MD, of the University of Ottawa in Canada. This can cause pain and skeletal-related events. “They are supportive care interventions, and therefore quality of life and patient-reported outcomes are essential,” he said. Clemons presented results of the new trial (abstract 11501) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago.
The study included a total of 263 patients, with 133 patients randomized to receive 4-weekly BTAs and 130 randomized to receive 12-weekly treatment; 3 patients in the 12-weekly group withdrew and 3 others were lost to follow-up. The per-protocol analysis included 85 patients in the 4-weekly group and 69 patients in the 12-weekly group.
In the full intention-to-treat population of 263 patients, the median age was 67 years in the 4-weekly group and 68 years in the 12-weekly group; 39.1% and 39.2% of patients in the 4-weekly and 12-weekly groups, respectively, had metastatic CRPC. In the 4-weekly group, 45.1% were BTA-naive, compared with 58.5% in the 12-weekly group. Patients were treated with denosumab most commonly (57.9% and 54.6%, respectively), followed by zoledronate (23.3% and 24.6%, respectively), and pamidronate (18.8% and 20.8%, respectively).
The primary outcome was health-related quality of life measured by the EORTC-QLQ-C30 functional domain-physical subdomain at 48 weeks. The median score at that point was 0 in both groups (P = .96), and the trial met the requirements for non-inferiority. Secondary outcomes were also similar, with no differences with regard to pain, global health status, and absolute rates of symptomatic skeletal events.
There was one case of osteonecrosis of the jaw in each group (P = 1.00). There were also identical numbers of cases of renal impairment (4 in each group; P = 1.00) and symptomatic hypocalcemia (3 in each group; P = 1.00). More patients in the 4-weekly group required a change in dosing schedule (36.1% vs 20.8%; P = .006).
Clemons noted that the study was limited by its open-label design and the primary endpoint being a patient-reported outcome. Still, he said the “data add to the body of evidence that we are not just seeing in metastatic cancer, but we are also seeing in the fragility/fracture world, where de-escalation of these highly potent agents is a reasonable treatment option.”
Silke Gillessen, MD, of Kantonsspital St. Gallen in Switzerland, was the discussant for the abstract, and she said the analysis was underpowered, making firm conclusions about non-inferiority difficult. “This study adds some interesting information, and reassuring information, but more data [are] needed,” she said.
She noted that the Swiss REDUSE trial is currently ongoing and will add further evidence to the field; almost 900 of a planned 1,380 patients have been recruited. “For the time being… for patients with metastatic CRPC, in my opinion there is not enough data yet for de-escalation, but we should consider a risk-adapted approach,” Gillessen said.