Prostate cancer: Better prognosis with a triple therapy

In a recent study, a significant improvement in PFS probability was observed in the treatment of patients with advanced castration-resistant prostate cancer through the use of ribociclib, docetaxel and prednisone.

Triple combination improves survival rate

In a recent study, a significant improvement in progression-free survival probability was observed in the treatment of patients with advanced castration-resistant prostate cancer through the use of ribociclib, docetaxel and prednisone. The results were presented at the ASCO Annual Meeting 2021.

Men with advanced prostate cancer often receive androgen deprivation as "chemical castration" in addition to radiotherapy and surgical intervention. In the case of androgen-independent or castration-resistant prostate carcinoma, this therapy option is no longer available. This limits the treatment options and has a negative effect on the prognosis of the patients.

Against this background, the current study of the University of California San Francisco (UCSF) investigated an alternative therapy approach consisting of a triple combination with ribociclib, docetaxel and prednisone. It is already known from preclinical studies that CDK4/6 inhibitors such as ribociclib show synergistic effects with taxanes. In contrast, no significant benefit could be shown with docetaxel as monotherapy.

First triple combination, then monotherapy with ribociclib

A total of 43 men with metastatic castration-resistant prostate cancer who had already received one or more therapies with androgen receptor signalling inhibitors but had not yet been treated with docetaxel were included in the study.

In the trial, patients received a triple therapy of docetaxel (60 mg/m2) and ribociclib (400 mg/d on days 2 to 14 of each 21-day cycle) and prednisone for six to nine cycles, followed by monotherapy with ribociclib until radiologically or clinically confirmed progression of the cancer. The dose-limiting factor was the toxicity of the agents. Two patients experienced severe neutropenia, so the initial dose of docetaxel (75 mg/m2/d) and ribociclib (200 mg/d) was reduced during the course of the study.

Progression-free for an average of eight months

The result of the study is that 65% of patients remained progression-free over the observed six-month period. The median progression-free survival is eight months, according to the authors. The PSA response rate, defined as at least a 50% reduction from baseline, was 27.6%.

During treatment with the triple combination, severe side effects (grade 3 or more) occurred in some of the patients. A total of 11 participants experienced neutropenia and 3 developed lymphocytopenia.

Identification of risk factors: high CTC levels and MYC or CDK6 overexpression

Two risk factors were also identified in the study: High CTC (circulating tumor cell) levels at baseline were associated with a greater risk of radiologically confirmed progression or death. In contrast, patients with detectable CTC who did not overexpress either the MYC gene or the CDK6 gene had a longer progression-free survival than patients with strong gene amplification.

"The combination of ribociclib and docetaxel was well tolerated and showed promising activity in metastatic castration-resistant prostate cancer in patients with progression under androgen deprivation," Kouchkovsky and colleagues summarise. "The phase-2 trial met its primary endpoint with an encouraging 6-month progression-free survival rate of 65%" adding that without MYC or CDK6 overexpression, the outcome was even better, they said.

Source:
ASCO Annual Meeting 2021, poster "Phase (Ph) 1b/2 study of ribociclib (R) in combination with docetaxel (D) plus prednisone (P) in metastatic castration-resistant prostate cancer (mCRPC)"

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