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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.

REFERENCE:

Provenzano L, Dieci MV, Curigliano G, et al. Real-world effectiveness comparison of first-line palbociclib, ribociclib or abemaciclib plus endocrine therapy in advanced HR-positive/HER2-negative BC patients: results from the multicenter PALMARES-2 study. Ann Oncol. 2025;36(7):762-774. doi:10.1016/j.annonc.2025.03.023

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A new study has identified bacterial isolates collected from Crete that are capable of killing mosquito larvae in laboratory tests, raising the possibility of developing biopesticides that target vector species while minimizing environmental impact. The findings, published in Applied and Environmental Microbiology, focus on bacterial strains that produce metabolites lethal to Culex pipiens molestus, a mosquito species known to transmit pathogens such as West Nile virus and Rift Valley fever virus.

Researchers exposed mosquito larvae to extracts derived from the metabolites of bacterial isolates obtained from soil, plants, water and dead insects collected across the island. More than 100 of the isolates tested killed all larvae within 7 days, and 37 did so in under 3 days. Three isolates achieved complete larval mortality within 24 hours. These results suggest that the metabolites produced by the isolates are rapidly acting and may offer a targeted form of mosquito control.

Targeted action with low ecological persistence

The study was conducted as part of the MicroBioPest project, a European Union–funded effort to explore microbial solutions for pest control. Researchers from the Institute of Molecular Biology and Biotechnology (IMBB) in Crete and Johns Hopkins University in Baltimore led the work.

The isolates represented 20 bacterial genera, many of which had not previously been associated with insecticidal activity. Importantly, the study found that the mosquito larvae were killed not through bacterial infection but through exposure to bioactive compounds. This characteristic may allow for the development of products that do not require live microbes to be effective, potentially simplifying formulation and delivery strategies.

Broader applications under investigation

The research team is currently working to identify the molecular composition of the insecticidal compounds. Their analyses aim to determine whether the active agents are proteins or other metabolites. In parallel, the isolates are being tested against other mosquito strains and agricultural pests to assess their broader pesticidal potential.

Biopesticides derived from microbial sources often have low persistence in the environment, breaking down more quickly than synthetic insecticides. While this characteristic reduces ecological accumulation, it may also necessitate repeated application to maintain efficacy. Future work will focus on the development of formulations that enhance stability and usability.

The study underscores the value of biodiversity in identifying new tools for pest management and highlights a potential pathway toward safer alternatives to conventional insecticides.

Reference: Wood MJ, Kanelli K, Silva JJ, et al. Bacteria isolated from biodiverse Mediterranean island habitats yield a large array of biopesticidal metabolites against mosquito larvae. Tortosa P, ed. Appl Environ Microbiol. 2025. doi: 10.1128/aem.00966-25

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