The temporal relationship between molecular and radiologic findings observed here suggests potential value for earlier detection of disease activity, although whether such lead time translates into improved clinical outcomes requires prospective validation. The findings support prospective evaluation of this approach, including the ongoing TROPHY trial investigating this therapeutic approach.

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

P2, N=182, Recruiting, Hebei Medical University Fourth Hospital

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.

Existing studies are generally limited by small sample sizes and a lack of long-term survival data, and high-level evidence directly comparing pyrotinib-based strategies with trastuzumab plus pertuzumab is scarce. Future research should prioritize biomarker-driven patient selection, response-adaptive trial designs, and standardized toxicity management to optimize clinical decision-making.

Kaplan-Meier survival curve and Cox regression model was used to analyze the effect of different levels of NLR and LDH before T-DM1 treatment on the survival of patients. Elevated NLR and LDH were associated with poor PFS and OS. Future data are needed to validate and update our results.

In a real-world setting the addition of pyrotinib to trastuzumab and chemotherapy significantly improved pathological and radiographic responses and prolonged PFS, albeit with an increased but manageable toxicity profile.

THPy may provide PFS benefit over THP in HER2+ MBC, with suggestive advantages in patients with de novo stage IV disease and liver metastasis. A higher frequency of diarrhea and other gastrointestinal toxicities was observed in the THPy regimen.

P4, N=500, Not yet recruiting, Peking University People's Hospital

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.