Nerlynx (neratinib)

P2, N=8, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=36 --> 8

Patient characteristics reflect current Chinese practice. Increasing adoption of diarrhoea prophylaxis in real-world practice reflects growing clinical experience with neratinib and its recognised benefit in preventing diarrhoea.

Treatment of HER2+ mBC with and without BMs in Saudi Arabia largely aligned with international recommendations identified in our literature analysis, although access to lapatinib, tucatinib and neratinib can be limited and may lead to use of alternative regimens. The tucatinib-combination may be considered the standard of care for adult patients with HER2+ locally advanced or mBC who have received at least two prior anti-HER2+ treatment regimens, including patients with BMs. Ensuring access to innovative HER2+ mBC therapies across Saudi Arabia is crucial to supporting best practice.

Planned treatment with a combination regimen of nivolumab and neratinib was scheduled; however, the patient deteriorated rapidly, and systemic therapy could not be initiated before death. This case was notable for advanced peritoneal carcinomatosis at presentation, severe thrombocytosis, and the diagnostic and therapeutic challenges posed by metastatic fibrolamellar carcinoma without molecular confirmation. Taken together, this underscores the importance of early recognition, molecular testing, and coordinated clinical management in optimizing outcomes for this uncommon malignancy.

P1, N=18, Active, not recruiting, Virginia Commonwealth University | Trial completion date: May 2029 --> Oct 2027

P2, N=109, Recruiting, Scott R. Plotkin, MD, PhD | Active, not recruiting --> Recruiting

P1/2, N=83, Recruiting, Virginia Commonwealth University | Trial completion date: May 2027 --> Jan 2031 | Trial primary completion date: May 2026 --> Dec 2029

FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.

The LAR subtype harbors two therapeutic vulnerabilities: ERBB2 mutation-driven kinase activation; and senescence-mediated immune evasion. The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype.

N+T in patients with HER2-mutant metastatic TNBC appeared to prolong responses versus neratinib alone, representing a novel approach for biomarker-defined metastatic TNBC patients. Based on these and previously published data, neratinib-based combinations are endorsed by NCCN guidelines for patients with hormone receptor-positive or -negative metastatic breast cancer with activating HER2 mutations.

They have demonstrated substantial improvements in survival-free and life expectancy of patients, establishing them as a standard treatment modality. The ongoing development of novel tyrosine kinase inhibitors and their strategic integration into personalized treatment regimens will shape the evolving landscape of breast cancer therapy.

BRD8 regulated ER-dependent and independent growth pathways, and depletion of BRD8 abolished neratinib-induced ER activation and restored drug sensitivity in resistant cells. A 3-gene BRD8 signature successfully predicted anti-HER2 therapy response in two human clinical trials. Together, these findings establish BRD8 as both a predictive biomarker for anti-HER2 response and a therapeutic target to overcome resistance in HR+/HER2+ breast cancer.