Son SM, et al. J Gastric Cancer. 2024 Dec;25:e2. https://doi.org/10.5230/jgc.2025.25.e2

Purpose Trastuzumab has markedly improved the survival outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and dual blockade of HER2 using trastuzumab and pertuzumab in combination with taxanes (THP) has become a standard of care for HER2-positive metastatic breast cancer (MBC) worldwide since the CLEOPATRA trial. We assessed the outcomes of THP as a first-line treatment for Korean HER2-positive MBC patients in the real-world setting. Materials and Methods Between August 2008 and October 2020, we identified 228 HER2-positive MBC patients who received THP as a first-line palliative chemotherapy. We analyzed survival outcomes, efficacy, and adverse events of THP retrospectively. Results After a median follow-up duration of 28.7 months, median overall survival and progression-free survival were 58.3 months (95% confidence interval [CI], 36.6 to 80.0) and 19.1 months (95% CI, 16.2 to 21.9), respectively. Better survival outcomes were observed in patient who received docetaxel for more than six cycles. Patients exposed to anti-HER2 directed therapies in a perioperative setting had poor survival outcomes. The overall response rate was 86.8% with a complete response (CR) rate of 17.7%. Among responders, 16.7% of patients sustained THP over 35 months and showed better survivals and higher CR rates. Adverse events were comparable to those reported in previous studies. Conclusion In a real-world context, clinical outcomes of Korean HER2-positive MBC patients treated with THP were similar to those of patients in the CLEOPATRA trial. Much longer follow-up results would be warranted.

Background: After the publication of the ABC-02 trial, gemcitabine and cisplatin combination therapy (GP) became the standard first-line treatment for advanced biliary tract cancer (BTC). Despite GP therapy, most patients suffer from disease progression. The ABC-06 trial recommended FOLFOX as a second-line treatment, but its efficacy was modest. In this phase II study, we looked at the efficacy and safety of a second-line modified dose of FOLFIRINOX (mFOLFIRINOX) for patients who had failed first-line gemcitabine-based treatment. Methods: From January 2020 to January 2021, 34 patients with advanced BTC who failed first-line gemcitabine-based chemotherapy were enrolled. We evaluated the clinical efficacy and safety outcomes of mFOLFIRINOX. Results: With a median follow-up duration of 13.4 months, the median progression-free survival and overall survival was 2.8 months (95% confidence interval (CI): 1.6–4.0 months) and 6.2 months (95% CI: 5.0–7.4 months), respectively. The objective response rate was 14.7% with no complete response. The disease control rate was 61.7%, with a disease control duration of 4.2 months. Due to the rapid progression of the disease, approximately half of all patients received less than three cycles of treatment. The most common type of adverse event (AEs) was hematopoietic AEs. The incidence of non-hematopoietic AEs was relatively low. Conclusions: The efficacy of mFOLFIRINOX as a second-line treatment in advanced BTC patients after the failure of gemcitabine-based first-line treatment was replicated, albeit with slightly shorter survival results compared to previous studies. Long-term administration of mFOLFIRINOX with toxicity management might offer a survival benefit.

Background. Follicular lymphoma (FL) is considered incurable because remission and relapse are common. Although various salvage treatment options have been proposed, there is no consensus on treatment strategy for FL patients who failed primary treatment. Methods. This single-center study analyzed postevent overall survival (OS) among 70 patients who experienced relapse or progression after rituximab-containing immunochemotherapy according to type of salvage treatment and nature of relapse or progression. Results. Of 70 patients, 42 experienced progression of disease within 24 months (POD24), and six showed disease progression during first-line treatment. Large-cell transformation was found in nine patients with POD24. At the median follow-up of 104 months (95 CI: 90-118 months), POD24 patients experienced significantly worse OS than patients without POD24, and postevent OS was not satisfactory after conventional salvage chemotherapy because the majority of patients relapsed or progressed. However, autologous stem cell transplantation (ASCT) after the first relapse resulted in survival prolongation in patients with POD24. Half of the patients (34/67, 51) participated in at least one clinical trial during treatment after first relapse, and patients participating in at least one clinical trial irrespective of line of treatment tended to experience better survival. Conclusions. Relapsed or refractory FL patients showed various clinical courses and treatment outcomes according to relapse or progression. Consolidation treatment with ASCT and active participation to clinical trials might prolong survival duration, especially in POD24 cases.

Background and Objectives: Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is involved in pancreatic cancer progression and is an attractive therapeutic target for pancreatic cancer. In this study, we evaluated the therapeutic efficacy of small-interfering RNA (siRNA) targeting CEACAM6 (siCEACAM6) and the CEACAM6-suppressive microRNA-29a (miR-29a) in a pancreatic ductal adenocarcinoma xenograft mouse model using pH-low insertion peptide (pHLIP) technology, which targets the acidic tumor microenvironment. Materials and Methods: The delivery vectors for siRNA and miRNA were constructed by conjugating the peptide nucleic acid forms of siCEACAM6 and miR-29a to a peptide with a pHLIP, enabling the transport of siRNA and miRNA across the plasma membrane. The tumor-suppressive effects of pHLIP-siCEACAM6 and pHLIP-miR-29a were assessed in vivo using a BALB/c xenograft mouse model with the injection of the CFPAC-1 human pancreatic ductal adenocarcinoma cell line. Results: The treatment of CFPAC-1 cells with pHLIP-siCEACAM6 and pHLIP-miR-29a under acidic pH conditions suppressed CEACAM6 expression and decreased cell viability. In a xenograft mouse model, the intravenous injection of pHLIP-siCEACAM6 and pHLIP-miR-29a suppressed tumor growth by up to 25.1% (p < 0.01) and 21.2% (p < 0.01), respectively, compared to the control mice treated with pHLIP-scr. Conclusions: Our results demonstrated the efficacy of the pHLIP-mediated delivery of siCEACAM6 and miR-29a as a promising therapeutic strategy in a pancreatic ductal adenocarcinoma xenograft mouse model. The pHLIP technology, which targets the acidic tumor microenvironment, represents an innovative approach to the delivery of small RNAs to pancreatic ductal adenocarcinoma cells, providing new potential strategies for pancreatic cancer treatment.