Sacituzumab govitecan (SG), a Trop-2-directed antibody-drug conjugate (ADC), was the first ADC approved for patients with metastatic triple-negative breast cancer (mTNBC) who had received at least two prior lines of therapy for advanced disease. Although SG has shown promising clinical activity in treating brain metastases in both ASCENT randomized trials and real-world analysis, its utility in leptomeningeal carcinomatosis (LC) remains underexplored. We report the diagnostic and therapeutic process of a patient who develops extensive LC from TNBC treated with SG. She presented a clinical response after the first cycle of SG with a PFS of 6 months. This case report highlights the need for further inquiry into the use of SG in LC.

This case report describes a 16-year-old patient with refractory Hodgkin\'s lymphoma who developed bilateral anterior and intermediate uveitis as an adverse reaction to Brentuximab vedotin (BV). This is a rare case of an ocular adverse reaction potentially related to BV, with symptoms like blurred vision, decreased visual acuity, photophobia, and redness. Potential mechanisms include BV targeting CD30+ T cells in the uveal tissue or an immune response triggered by the microtubule-disrupting agent MMAE within BV. This highlights the need for vigilant monitoring of ocular adverse events in BV-treated patients and further research into their mechanisms and management.

Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.

UNASSIGNED: The study of bladder preservation for muscle-invasive bladder cancer (MIBC) mainly focuses on the T2 stage, which remains difficult in the T3 and T4 stage. Pembrolizumab has been applied as neoadjuvant therapy followed by radical cystectomy for MIBC, gaining encouraging results in the phase II study. Disitamab vedotin, an antibody-drug conjugate (ADC), also achieved promising efficacy for refractory bladder cancer. However, the neoadjuvant therapy strategy of these drugs for bladder sparing remains further exploration.
UNASSIGNED: A patient with locally advanced MIBC at our institute underwent a neoadjuvant therapeutic regimen followed by transurethral resection of bladder tumor (TURBT) and concurrent chemoradiotherapy. In light of limited initial efficacy, we enacted an adaptive shift in the neoadjuvant treatment strategy, transitioning from a combination of gemcitabine, cis-platinum, and pembrolizumab to disitamab vedotin with pembrolizumab. This approach ultimately achieved bladder preservation, complete response, and a remarkable 1-year disease-free survival (DFS).
UNASSIGNED: Proactive evaluation in the early stages of tumor downstaging can serve as a guiding principle for neoadjuvant strategies. This is the first successful case of neoadjuvant pembrolizumab combined with disitamab vedotin and chemotherapy in MIBC patients achieving complete response and bladder preservation.

UNASSIGNED: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare subtype of T-cell leukemia that phenotypically expresses mature T-cell markers and immature myeloid markers such as CD33. Gemtuzumab ozogamicin (GO) is a novel agent for the CD33 molecular targeting antibody conjugated to the cytotoxic agent calicheamicin. GO is anticipated to be effective against ETP-ALL. In vivo studies promise antileukemic effects in cell lines; however, clinical reports to support this research are lacking. We treated a patient who suffered from CD33-positive ETP-ALL using GO.
UNASSIGNED: We treated an 81-year-old man who suffered from ETP-ALL. The patient\'s leukemia expressed T cell and myeloid markers including cyCD3, CD5, CD7, CD33, and HLA-DR. Initially, the patient was treated using a standard chemotherapy regimen for acute lymphoblastic leukemia comprising cyclophosphamide, daunorubicin, vincristine, l-asparaginase, and prednisolone. The induction chemotherapy produced the expected complete hematological response; however, bone marrow blasts remained. Following consolidation chemotherapy, the patient maintained a full hematological response. Thereafter, we changed the consolidation regimen to nelarabine, which did not reduce bone marrow blasts effectively. After two courses of nelarabine therapy, we finally used GO at an 8 mg/m2 weekly dose after confirming that CD33 expression was still positive in the patient\'s residual leukemic cells. GO was ineffective in treating the patient\'s leukemia, and peripheral blasts increased 30 days following treatment. The patient died 81 days after initiating GO therapy.
UNASSIGNED: This is the first clinical case of GO having a negative impact on ETP-ALL. Because the GO resistance mechanism for ETP-ALL has not been fully elucidated, treatment modification should be considered to achieve optimal clinical efficacy.

This case report describes the treatment of a patient diagnosed with de novo stage 4 human epidermal growth factor 2 (HER2)-positive gastric adenocarcinoma with enteroblastic differentiation (GAED), a rare and aggressive form of gastric cancer characterized by a tubulopapillary growth pattern and enteroblastic cell lineage markers such as GPC3, SALL4, and alpha fetoprotein. Given the patient\'s symptomatic, advanced-stage cancer, treatment objectives were focused on effectively deterring disease progression and ameliorating symptoms throughout the anticipated multiple lines of therapy. Subsequent to standard first- and second-line therapies for HER2-positive metastatic GC, third-line treatment using the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) for seven cycles resulted in satisfactory tumor control and well-preserved physical performance and quality of life, with minimal hematologic and pulmonary toxicities. The patient retained acceptable physical performance to receive subsequent lines of therapies, and still showed a tumor marker response to 5L trastuzumab-based chemotherapy. As the tumor was positive for both HER2 and programmed death-ligand 1 (PD-L1) expressions, the selection and sequencing of anti-HER2 and anti-PD-L1 therapies were discussed in relation to the latest U.S. Food and Drug Administration approvals and trial results.

Options for later-line therapy are limited for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who have exhibited resistance to several systemic treatments. Antibody drug conjugates (ADCs) and immune checkpoint inhibitors are novel approaches for HER2-positive breast cancer, but few reports have been published regarding the efficacy of their combinations, particularly in patients with prior ADC failure. The present report describes a case of recurrent metastatic HER2-positive breast cancer, which responded poorly to several perioperative systemic therapies, including chemotherapies, HER2-targeted antibodies, small molecule inhibitors and trastuzumab emtansine (an ADC), along with post-surgical radiotherapy. Following failure of front-line therapies for recurrent cancer located in the chest wall, combination treatment with another HER2-targeted ADC, disitamab vedotin (120 mg), and zimberelimab (240 mg), a fully humanized anti-programmed cell death protein-1 (PD-1) antibody, administered intravenously every 2 weeks, was initiated. The tumor lesions improved slightly after two cycles of treatment and shrunk markedly, and almost disappeared at the end of the sixth cycle of therapy. The patient is still in remission at present. The present findings suggest the potential efficacy of HER2-targeted ADCs combined with PD-1 inhibitors for patients with HER2-positive breast cancer, including those resistant to prior HER2-targeted ADCs.

UNASSIGNED: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, owing to its high metastatic potential: Patients who develop brain metastases (BMs) have a poor prognosis due to the lack of effective systemic treatments. Surgery and radiation therapy are valid options, while pharmacotherapy still relies on systemic chemotherapy, which has limited efficacy. Among the new treatment strategies available, the antibody-drug conjugate (ADC) sacituzumab govitecan has shown an encouraging activity in metastatic TNBC, even in the presence of BMs.
UNASSIGNED: A 59-year-old woman was diagnosed with early TNBC and underwent surgery and subsequent adjuvant chemotherapy. A germline pathogenic variant in BReast CAncer gene 2 (BRCA2) was revealed after genetic testing. After 11 months from the completion of adjuvant treatment, she had pulmonary and hilar nodal relapse and began first-line chemotherapy with carboplatin and paclitaxel. However, after only 3 months from starting the treatment, she experienced relevant disease progression, due to the appearance of numerous and symptomatic BMs. Sacituzumab govitecan (10 mg/kg) was started as second-line treatment as part of the Expanded Access Program (EAP). She reported symptomatic relief after the first cycle and received whole-brain radiotherapy (WBRT) concomitantly to sacituzumab govitecan treatment. The subsequent CT scan showed an extracranial partial response and a near-to-complete intracranial response; no grade 3 adverse events were reported, even if sacituzumab govitecan was reduced to 7.5 mg/kg due to persistent G2 asthenia. After 10 months from starting sacituzumab govitecan, a systemic disease progression was documented, while intracranial response was maintained.
UNASSIGNED: This case report supports the potential efficacy and safety of sacituzumab govitecan in the treatment of early recurrent and BRCA-mutant TNBC. Despite the presence of active BMs, our patient had a progression-free survival (PFS) of 10 months in the second-line setting and sacituzumab govitecan was safe when administered together with radiation therapy. Further real-world data are warranted to confirm sacituzumab govitecan efficacy in this patient population.

Cancer therapies targeting human epidermal growth factor receptor 2 (HER2) have been attracting increasing attention worldwide, especially in lung adenocarcinoma. Disitamab vedotin is an antibody-drug conjugate designed for targeting HER2 that has been approved for urothelial carcinoma and gastric cancer. However, there is still a lack of clinical evidence for applying Disitamab vedotin in lung adenocarcinoma. Herein, we reported a case of a 52-year-old man with advanced lung adenocarcinoma carrying HER2 amplification as well as HER2 immunohistochemistry (IHC) 2 + who underwent treatment with Disitamab vedotin after disease progression. The patient was treated with chemotherapy, anti-angiogenesis therapy, and immunotherapy as first-line therapy, achieving a remarkable progression-free survival of 16 months. After the disease continued to continuous progress, the patient was administrated with Disitamab vedotin, which resulted in improvement of both the lung lesions and the brain lesions. Our findings provide a valuable reference for the utilization of Disitamab Vedotin in HER2 IHC2+ lung adenocarcinoma.

OBJECTIVE: Trastuzumab-emtansine is an antibody-drug conjugate developed to decrease off-target toxicity. According to the product label, reactions secondary to extravasation are mild or moderate.
METHODS: We report on a 51-year-old woman who developed epidermal necrosis after extravasation of trastuzumab-emtansine, which required surgical intervention. Six weeks later, the lesions were healed with residual hyperpigmentation.
CONCLUSIONS: We describe the course of a case of severe toxicity following trastuzumab-emtansine extravasation. We provide treatment recommendations and recommend amending the information on the product label on extravasation.