HER-2 exon 20 mutation

DS-8201 demonstrates potential as one of the effective salvage therapies following RC48 failure in HER2 altered solid tumors, showing significantly better disease control and a distinct, manageable toxicity profile. These findings highlight the importance of selecting personalized ADCs based on molecular subtypes and toxicity factors and provide a basis for future, larger-scale prospective studies.

In this small case series, T-DXd demonstrated encouraging antitumor activity and manageable safety in heavily pretreated patients with HER2 mutated, metastatic NSCLC. Although selected patients had durable benefits, the findings are anecdotal and should be interpreted with caution. Larger real‑world cohorts and prospective studies are needed to validate the consistency, durability, and safety of T‑DXd in routine clinical practice.

This study enriches the current volume of evidence on histopathologic, genetic, immunologic correlates of PD-L1 expression and, to our knowledge, is the first comprehensive analysis of arm-level alterations. Further studies are warranted to validate these finding and to determine their associations with clinical outcomes.

In contrast, such changes in CD8 + T cell infiltration and PD-1 expression were not evident in another HER2 20ins patient who received conventional chemotherapy. These findings suggest that neoadjuvant T-DXd may represent a promising therapeutic option for locally advanced HER2-mutant NSCLC, warranting further investigation in larger cohorts.

Progression-free survival was longer with targeted therapies compared with immunotherapy ± chemotherapy, although overall survival remained similar. This study provides the first integrated clinical and molecular characterization of lung adenocarcinoma in the French West Indies and highlights the urgent need to improve early diagnosis, molecular testing access, and treatment initiation in underserved island populations.

The second case involves a patient with metastatic micropapillary urothelial carcinoma with HER2 expression, refractory to platinum chemotherapy, avelumab maintenance, and enfortumab vedotin. These two observations illustrate the capacity of T-DXd to induce deep and complete metabolic remissions in distinct HER2-altered solid tumors. They support further development of HER2-targeted ADCs beyond traditional indications and highlight the value of FDG-PET/CT for assessing the depth of response to these agents.

She enrolled in a clinical trial of the selective HER2 tyrosine kinase inhibitor zongertinib (60 mg twice daily) in February 2025 and tolerated therapy well, with mild diarrhea, lactose intolerance, brittle nails, and intermittent muscle cramps...As of January 2026, she has maintained lung-confined disease control for over 11 months without extrapulmonary progression and remains fully functional without symptoms. This case highlights the clinical benefit and tolerability of selective HER2-targeted therapy in HER2-mutant NSCLC and adds to emerging evidence supporting consideration of risk-based lung cancer screening strategies in high-risk never-smoking populations.

The study underscores the importance of integrating NGS-based molecular testing with PD-L1 evaluation for personalised management of NSCLC. Distinct patterns of PD-L1 expression across molecular subtypes, particularly lower in EGFR-mutated tumours and higher in KRAS-mutated tumours, underscore the need for tailored therapeutic strategies and informed sequencing of targeted therapies and immunotherapies.

This case is the first to elucidate the putative resistance mechanisms to zongertinib in HER2-mutant lung adenocarcinoma might be transformation of adenosquamous with giant-cell carcinoma and acquired HER2 amplification through integrated histological and molecular analyses. These findings highlight the necessity of post-progression biopsy and genomic profiling to characterize resistance evolution and guide subsequent therapy selection.

Following isolation by prep-HPLC, 1D and 2D NMR studies and HRMS characterization assigned the isolate as Mobocertinib-N-oxide. In addition, NMR-based reaction monitoring was conducted to trace its formation, allowing a plausible mechanism of formation to be proposed.

PNST harboring oncogenic ERBB2 mutations are multifocal, spanning various neurofibroma variants, including plexiform type, in the absence of clinical or germline evidence of syndromic disease. Our findings suggest ERBB2 mutations may represent an alternative mechanism driving neurofibroma genesis, with potential therapeutic implications.

The management of human epidermal growth factor receptor 2 (HER2)-mutant non-small cell lung cancer (NSCLC) remains a significant clinical challenge, with limited effective and accessible treatment options beyond antibody-drug conjugates such as trastuzumab deruxtecan (T-DXd)...Following chemotherapy and sintilimab failure in August 2025 due to progressive disease, furmonertinib rechallenge at 160 mg/day again induced a response within 5 days, with no grade ≥3 adverse events...The structural homology between HER2 p.Y772_A775dup and EGFR exon 20 "near-loop" insertions may facilitate TKI binding. Furmonertinib emerges as a potential, cost-effective oral therapeutic alternative for this patient population, especially when standard therapies are not feasible, warranting further prospective investigation.