HER-2 positive + HER-2 overexpression

P2, N=19, Active, not recruiting, Nancy Lin, MD | Trial completion date: Dec 2025 --> May 2026

All patients received standard neoadjuvant chemotherapy (FLOT, XELOX, or FOLFOX) followed by curative gastrectomy with D2 lymphadenectomy...HER2 overexpression is associated with poorer pathological response to standard neoadjuvant chemotherapy in gastric adenocarcinoma. These findings highlight the potential need for molecularly tailored perioperative treatment strategies in this subgroup.

Recent advancements in cancer molecular profiling and the Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive pan-tumor indications have highlighted the broader relevance of HER2 alterations across diverse cancers...To address this gap, a multidisciplinary panel of Chinese experts has developed a consensus providing comprehensive recommendations on diagnostic strategies, testing methodologies, and clinical applications of HER2 overexpression detection. By establishing a unified framework for HER2 overexpression assessment, this consensus aims to enhance the precision of HER2 testing, optimize patient selection for targeted therapies, and improve clinical outcomes across a wide spectrum of HER2 overexpression malignancies.

Of note, 6/7 cases with HER-2 mutations exhibited limited benefit from treatment with FOLFIRI plus cetuximab with PFS inferior to 8 months. Taken together, these results highlight the need to test HER-2 gene alterations for patients with RAS/BRAF V600 WT, MSS mCRC, who are candidates for anti-epidermal growth factor receptor therapies.

The rHER2 ECD mRNA-LNP effectively circumvents HER2-specific immune tolerance. As a potent and safe platform, it induces robust coordinated humoral and cellular immunity and significantly enhances checkpoint blockade efficacy via the enrichment of TRM cells in the TME, which underscores its promising potential for the treatment of HER2-positive cancers.

Human epidermal growth factor receptor 2 (HER2) overexpression is a key therapeutic target for novel antibody-drug conjugates (ADCs) like disitamab vedotin (RC48) in bladder urothelial carcinoma (BLCA), but immunohistochemistry-based assessment is limited by intratumoral heterogeneity and sampling bias...The multimodal model significantly outperformed all single-modality models. A tri-phasic CT-based multimodal model enables noninvasive assessment of HER2 expression status in BLCA, providing a promising tool for selection of patients likely to benefit from ADC therapy.

The kidneys were the primary dose-limiting organ. [68Ga]Ga/[177Lu]Lu-NOTA-NB46 represents a promising radiotheranostic pair for HER2-positive tumors, supporting its further translation into clinical investigation.

Our patient presented with a visceral crisis denoted by impending liver failure, prompting the urgent initiation of first-line systemic therapy with fluorouracil, leucovorin, oxaliplatin and trastuzumab. This resulted in rapid clinical improvement, normalisation of liver function tests and tumour markers, and radiographic response with approximately 50% reduction in hepatic metastatic disease burden. This case underscores the aggressive behaviour and rarity of HER2-positive, AFP-producing gastric cancer, highlighting the critical need for prompt diagnosis and initiation of systemic therapy.

This multicenter retrospective study included 290 female patients diagnosed with HER2-positive early or locally advanced breast cancer treated with neoadjuvant trastuzumab and pertuzumab-based regimens (anthracycline-based [AC-THP] or non-anthracycline [TCHP]) across six centers. pCR remains the strongest surrogate for survival, neutralizing initial risk factors. These findings support using quantitative biomarker thresholds for personalization and reinforce the efficacy of non-anthracycline regimens.

Although the sample size is small, these findings support the clinical benefit of zanidatamab treatment for HER2-positive SGC.

P1/2, N=270, Completed, Dragonfly Therapeutics | Recruiting --> Completed | Trial completion date: Dec 2026 --> Dec 2025 | Trial primary completion date: Oct 2026 --> Dec 2025

These cases suggest that systemic HER2-targeted therapy can serve as an effective neoadjuvant approach for locally advanced HER2-positive SGCs. Conversion surgery following Tmab and DTX treatment may offer a curative option in selected patients initially deemed inoperable.