Real-world study shows differential efficacy of CDK4/6 inhibitor reboxil in advanced breast cancer

According to published results from the multicenterPALMARES-2 trial (NCT06805812), among patients with endocrine-sensitive HR-positive/HER2-negative advanced breast cancer 6i) Abemaciclib, palbociclib and ribociclib show different real-world progression-free survival (rwPFS) outcomes After a median follow-up of 34.1 months, abeciclib and palbociclib were associated with significantly longer rwPFS compared to palbociclib.

The adjusted hazard ratio (aHR) for abeciclib versus palbociclib was 0.76 (95% confidence interval, 0.63-0.92; P=0.004), whereas the aHR for reboxiclib versus palbociclib was 0.83 (95% confidence interval, 0.73-0.95; P=0.007). No significant difference was observed between abeciclib and reboxil (aHR, 0.91; 95% CI, 0.73-1.14; P=0.425).

Among patients with endocrine-sensitive diseases, only abeciclib was associated with betterrwPFS compared with palbociclib (aHR, 0.75; 95% CI, 0.64-0.87; P<0.001). According to the researchers, abeciclib and rebociclib were more effective than palbociclib in patients who were premenopausal or had endocrine resistance or luminal B-like disease (aHR 0.77; 95% CI, 0.63-0.93, P=0.008; rebociclib vs palbociclib: aHR 0.75; 95% CI, 0.58-0.98; P=0.034). Abeciclib was more effective than rebociclib and palbociclib in patients with de novo metastatic disease and more effective than palbociclib in patients with poor ECOG performance. All 3 CDK4/6is were equally effective in patients with pure bone disease.

A total of1982 patients were registered at 18 Italian cancer centers where they received physician's choice of palbociclib (n=789), rebociclib [n=736] or abeciclib [n=457] for first-line treatment of HR-positive, HER2-negative advanced cancer. Data were collected from electronic health records at each participating center.

The primary endpoint isrwPFS, defined as the time interval from the initiation of estrogen therapy (ET) plus CDK4/6is to the detection of disease progression, was assessed according to radiological (CT/PET scan), clinical (clinical tumor measurement and evolution of patient status) or biochemical criteria (CA15.3 measurement) or patient death (whichever occurred first).

Secondary endpoints compared rwPFS associated with3 CDK4/6i in clinically relevant patient cohorts, such as premenopausal patients, elderly patients (age >75 years at CDK4/6i initiation) or patients with liver metastases, pure bone disease, luminal B-like tumors, de novo metastatic disease, or patients with poor ECOG performance (≥1). Exploratory endpoints including time to next treatment or death, distance to chemotherapy or death, and overall survival were also explored.

After receiving palbociclib (n=395, 50.9%), rebociclib (n=349, 48.7%) and abeciclib (n=233, 52.4 %), the frequency of dose reductions was similar, with 484 (61.5%), 290 (39.4%), and 183 (40.0%) permanently discontinuing CDK4/6i for any reason, respectively. Discontinuations were attributed to disease progression (n=864, 43.6%), hematological, gastrointestinal and/or hepatic toxicity (n=50, 2.5%), or other toxicities/causes (n=43, 2.2%).

These results are unique in the field and compared in a real-world setting3 Published work on CDK 4/6i mostly consists of relatively small case series and lacks sufficient power to compare effectiveness. The researchers also noted some limitations of the study, including its retrospective and observational nature and the possibility that prescription of one or another CDK 4/6e was affected by the timing of individual drug approvals and registrations.

Reference materials:https://www.targetedonc.com/view/real-world-study-shows-differences-in-efficacy-among-cdk4-6-inhibitors-for-advanced-breast-cancer