HER-2 amplification

Dual HER2-targeted therapy combined with chemotherapy is a promising strategy for HER2-positive mCRC patients with good performance status. This approach warrants validation in large-scale clinical trials to confirm its efficacy.

ERBB2 amp+ mCRC is a small but clinically relevant subgroup with inferior rwPFS across current first-line treatments, highlighting the need for better strategies.

Our study shows that CTCs provide key information that would have been missed by ctDNA monitoring alone and extends CTC and cfDNA genomic profiling to patients with a broad range of CTC counts for blood-based monitoring of HER2 status and other clinically actionable targets for informing treatment decisions in metastatic disease.

Trastuzumab-based therapy has shown survival benefit in HER2-positive SEC, leading to its inclusion in current treatment guidelines...The prognostic value remains debated, though recent trials of antibody-drug conjugates (e.g., T-DXd) show promise...Diagnostic challenges include variable scoring systems, intratumoral heterogeneity, and HER2-low classification. Standardization of testing criteria and further clinical validation of HER2-targeted strategies across gynecologic tumors are essential to guide personalized therapy and improve outcomes.

Hb 100 ng/mL, height >160 cm, and the presence of lymph node metastases were associated with HER2 expression and positivity. HER2 testing should be considered mandatory when all these factors are present. The mechanisms linking these four factors to HER2 expression require further investigation.

ECs with MECOM amplification are associated with poor clinical outcomes, even in the absence of CCNE1 or ERBB2 amplification. The current literature is limited, and further studies are warranted to determine the role of MECOM amplification in ECs.

P2, N=18, Recruiting, Peking Union Medical College Hospital | N=45 --> 18 | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P2, N=33, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | N=185 --> 33 | Trial completion date: Feb 2026 --> Dec 2024 | Recruiting --> Terminated; Abandon of the partner, ROCHE

P2, N=51, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 --> Feb 2025 | Suspended --> Terminated; Abandon of the partner, GSK

ERBB2 focal amplification is associated with improved outcomes in trastuzumab-treated patients with HER2-positive gastric cancer, whereas NOTCH3 alterations predict a poor prognosis. These genomic features may support risk stratification and therapeutic decisions.

Temporal analysis showed conversion rates of 50.0% for synchronous metastases, 30.8% within 12 months, and 63.6% beyond 12 months. We identified a high prevalence of HER2-low and HER2-ultralow subtypes, suggesting potential eligibility for ADC therapies.

It demonstrates that targeting these lesions can yield outcomes that meet or exceed the benchmarks set by the NAPOLI-1 trial (liposomal irinotecan plus 5-fluorouracil and leucovorin), with a median overall survival of 6.2 months and progression-free survival of 3.1 months. Objective response rates reach 33% with adagrasib in KRAS G12C PDAC, 22% with olaparib maintenance in germline BRCA1/2 cancers, and over 50% with RET or NTRK inhibitors with fusion alterations; pembrolizumab produces durable benefit in the 1-3% of tumours that are MSI-H/dMMR. Emerging data highlight NRG1 fusions (overall response rate 42% with zenocutuzumab), HER2 amplification, MTAP deletion with PRMT5 dependency and variant-specific (MRTX1133) or pan-RAS (daraxonrasib) inhibitors as the next frontier...Taken together, these advances represent a substantive therapeutic progress in PDAC over the past decades, even though they currently apply to a minority of patients. These findings underscore the necessity of comprehensive next-generation sequencing for every patient with advanced disease, enabling identification of rare, yet clinically meaningful, targets and moving PDAC management towards a precision-oncology paradigm.