Medical illustration of breast cancer
In patients with endocrine-sensitive HR-positive/HER2-negative advanced breast cancer, the cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) abemaciclib (Verzenio), palbociclib (Ibrance), and ribociclib (Kisqali) demonstrated varying real-world progression-free survival (rwPFS) outcomes, according to findings from the multicenter PALMARES-2 trial (NCT06805812) published in Annals of Oncology.1
After a median follow-up of 34.1 months, abemaciclib and ribociclib were associated with significantly longer rwPFS compared with palbociclib. The adjusted hazard ratio (aHR) for abemaciclib versus palbociclib was 0.76 (95% CI, 0.63-0.92; P =.004), whereas ribociclib vs palbociclib showed an aHR of 0.83 (95% CI, 0.73-0.95; P =.007). No significant difference was observed between abemaciclib and ribociclib (aHR, 0.91; 95% CI, 0.73-1.14; P =.425).
In patients with endocrine-sensitive disease, only abemaciclib was associated with better rwPFS when compared with palbociclib (aHR, 0.75; 95% CI, 0.64-0.87; P <.001). In patients who were premenopausal or had endocrine-resistant or luminal B-like disease, abemaciclib and ribociclib were more effective than palbociclib (aHR 0.77; 95% CI, 0.63-0.93, P =.008; ribociclib vs palbociclib: aHR 0.75; 95% CI, 0.58-0.98; P =.034), according to investigators. Abemaciclib was more effective than ribociclib and palbociclib in patients with de novo metastatic disease, and more effective than palbociclib in patients with poorer ECOG performance status. All 3 CDK4/6is were similarly effective in patients who had bone-only disease.
Study Details
A total of 1982 patients were enrolled across 18 Italian cancer centers, in which they received either palbociclib (n = 789), ribociclib (n = 736), or abemaciclib (n = 457), determined by physician choice, in the first-line treatment of HR-positive, HER2-negative advanced breast cancer. Data were collected from electronic health records in each participating center.
Overall, the median age was 63 years (range, 53-72) and of the 1982 patients, 33% had endocrine-resistant tumors, 18% were premenopausal, and 30% had de novo metastatic disease. Abemaciclib-treated patients were more likely to have endocrine-resistant disease, liver metastases and lower progesterone receptor tumor expression, while patients receiving ribociclib were younger and more likely to be premenopausal; finally, palbociclib was more commonly prescribed to patients with a poorer ECOG performance status.
The primary end point was rwPFS, defined as the time interval between the initiation of estrogen therapy (ET) plus CDK4/6is and the detection of disease progression, as evaluated according to radiological (CT/PET scans), clinical (clinical tumor measurements and evolution of patient status), or biochemical criteria (CA15.3 measurements), or patient death, whichever occurred first.
Secondary end points compared the rwPFS associated with the 3 CDK4/6is in clinically relevant patient cohorts, such as premenopausal patients, older patients (age >75 years at the time of CDK4/6i initiation) or patients with liver metastases, bone-only disease, luminal B-like tumors, de novo metastatic disease, or poor ECOG performance status (≥ 1).
Exploratory end points were also explored and included time to next treatment or death, time to chemotherapy or death, and overall survival.
Treatment Discontinuation
Any dose reduction occurred with similar frequency in patients receiving palbociclib (n = 395, 50.9%), ribociclib (n = 349, 48.7%) and abemaciclib (n = 233, 52.4%), and permanent CDK4/6i discontinuation rates for any reason were 484 (61.5%), 290 (39.4%) and 183 (40.0%), respectively. Discontinuation was attributed to disease progression (n = 864, 43.6%), hematological, gastrointestinal and/or liver toxicities (n = 50, 2.5%), or other toxicities/reasons (n = 43, 2.2%).
According to Provenzano et al, “these results…are unique in the field with published works comparing the 3 CDK 4/6is in the real-world setting mostly consist[ing] of relatively small case series lacking sufficient power for effectiveness comparisons…” The investigators also noted a number of limitations with the study, including its retrospective and observational nature and that the prescription of one or another CDK 4/6i may have been influenced by the time of approval and registration of the individual agents.