Verzenio (abemaciclib)

Omission of SLNB in patients with small HR-positive/HER2-negative tumors results in a missed indication for CDK4/6i in <8 % with minimal impact on recurrence.

The advent of CDK4/6 inhibitors, namely, palbociclib, ribociclib and abemaciclib, has changed the management of oestrogen receptor (ER)-positive/HER2-negative advanced breast tumours. Nonetheless, the acquired resistance to CDK4/6 inhibitors remains a major therapeutic challenge. Thus, the identification of molecular drivers involved in the resistance to these drugs is crucial for the design of novel therapeutic approaches and the selection of patient-centred strategies in various types of tumours.

Clinical data indicate a higher incidence of nephrotoxic adverse reactions in patients receiving CDK4/6i compared to control groups, with abemaciclib showing the highest risk ratio...Preclinical studies suggest a complex effect on renal health; while some data indicate acute nephroprotection, long-term rodent models treated with palbociclib after ischemic AKI demonstrated impaired recovery, increased renal fibrosis, and cellular senescence, indicating potentially detrimental long-term chronic effects...Furthermore, these agents are susceptible to significant drug-drug interactions, particularly with CYP3A4 inhibitors/inducers and immunosuppressants, necessitating careful dose adjustments and monitoring, especially in solid organ transplant recipients. This review consolidates current evidence regarding the renal of CDK4/6i, emphasizing the need for vigilant monitoring and a multidisciplinary approach to optimize patient outcomes.

P2, N=162, Completed, MedSIR | Active, not recruiting --> Completed

CARABELA trial results suggest that 12 months of letrozole/abemaciclib may not offer similar efficacy to that of chemotherapy in achieving RCB 0-I. However, in less proliferative tumors (RS <26 or Ki-67 <30%), outcomes were comparable, suggesting that letrozole/abemaciclib could replace (neo)adjuvant chemotherapy in selected patients.

The combination therapy provides a clinically significant improvement in survival and treatment responses, even though the toxicity is increased but manageable, and requires careful prescription.

Real-world data reveal drug- and age-specific toxicity differences. Ribociclib and abemaciclib pose higher risks in older adults compared to palbociclib, supporting the need for personalized treatment and careful monitoring in older patients.

Ribociclib (Ribo) and Abemaciclib (Abe) are new-generation CDK inhibitors approved for use in breast cancer treatment. Some molecular mechanisms were elucidated by revealing the synergistic effect of FA combined with Ribo and/or Abe in both HR positive and HR negative breast cancer and its possible toxicity or protection on normal breast cells. The present findings suggest that FA is a viable candidate for adjuvant or neoadjuvant treatment in combination with Ribo and/or Abe, as an alternative to Letrozole or Fulvestrant, which have been associated with significant adverse effects in clinical settings.

Conversely, T-DXd administered due to the presence of HER2-low showed excellent effectiveness. Performing a re-biopsy is crucial due to the possible loss of estrogen receptors, which would require a change in therapeutic strategy no longer based on endocrine therapy. In cases that remain luminal, knowledge of the mutational profile may help to offer patients novel targeted treatments.

Patients with metastatic HR+HER2- IBC demonstrated a shorter time on treatment suggesting shorter duration of response on CDKI + HT, which is markedly inferior to reported data for non-IBC patients from phase III trials.

Dabrafenib plus trametinib has shown superiority over chemotherapy in pediatric low-grade gliomas and activity against high-grade diseases. Larotrectinib and entrectinib provide tumor-agnostic options for NTRK-fusion-positive tumors with central nervous system penetration. Selumetinib offers clinical benefits in NF1-associated plexiform neurofibromas and shows promise for treating NF1-related low-grade gliomas. Tovorafenib, a type II RAF inhibitor active in BRAF-altered tumors (including BRAFKIAA1549 fusion), achieved robust responses, thereby leading to FDA approval. ONC201 (dordaviprone) has received accelerated approval for the treatment of H3 K27M-mutant diffuse midline gliomas, with Japanese trials and patient-initiated programs expanding access. Abemaciclib, a CDK4/6 inhibitor, is under phase II evaluation for pediatric high-grade glioma and diffuse midline glioma, including sites in Japan. Neurosurgeons play a pivotal role in securing high-quality biopsies, thus enabling comprehensive molecular diagnostics and facilitating enrollment in international trials. This review summarizes current targeted therapies and ongoing studies and outlines practical considerations for integrating precision oncology into pediatric neuro-oncology in Japan.

At a WTP threshold of $150,000 per evLY, the probability that ribociclib is cost-effective versus abemaciclib, which was 81%. Ribociclib improves health outcomes with a modest impact on costs and is likely to be more cost-effective than abemaciclib for postmenopausal women requiring 1 L treatment of HR+/HER2- aBC from a Medicare perspective.