CF33-hNIS-anti-PD-L1 oncolytic virus followed by trastuzumab-deruxtecan in a patient with metastatic triple negative breast cancer: a case study.

Prognosis of metastatic triple negative breast cancer (mTNBC) remains poor despite recent advances in therapeutic options. Trastuzumab deruxtecan (T-DXd) has shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, which is defined by immunohistochemistry (IHC) 1+ or 2+ and lack of HER2 amplification by fluorescence in situ hybridization (FISH) testing. The purpose of the study is to evaluate the safety and initial evidence of efficacy of intratumoral administration of CF33-hNIS-anti-PD-L1 (CHECKvacc) against mTNBC. Oncolytic virus CHECKvacc intratumoral injection is currently undergoing investigation in patients with mTNBC as a single agent (NCT05081492). The patient was enrolled on the clinical trial CHECKvacc for the Treatment of Metastatic Triple Negative Breast Cancer, received a single dose of CHECKvacc, and discontinued the study due to lack of immediate response. We report a case of a patient with mTNBC who was heavily pretreated and presented with extensive dermal metastasis. Two dermal metastasis biopsies in 2021 showed HER2 0 by IHC. The patient received a single dose of CHECKvacc and discontinued the study due to lack of immediate response. Twenty-five days later, the patient received treatment with T-DXd, and her tumor regressed significantly. The patient's disease-free survival was 10 months (December 2021-October 2022). The sequential treatment with intratumoral injection of CHECKvacc followed by T-DXd may have significant clinical activity in select patients with heavily pretreated mTNBC. ClinicalTrials.gov NCT05081492.

Treatment of Patients Hospitalized with COVID-19 in a US Military Role 3 Facility in Afghanistan: A Case Series.

BACKGROUND: COVID-19, caused by SARS CoV-2, is an acute respiratory viral illness. We present the experience of treating patients hospitalized with COVID-19 in a Role 3 hospital in an active warzone. METHODS: This is a retrospective care series of patients treated for COVID-19 at Craig Joint Theater Hospital, Bagram, Afghanistan from May to August 2020. Data extracted included demographics, admission and disposition information, past medical history, comorbidities, Transportation Command (TRANSCOM) severity classification (i.e. Category A, Category B), and treatments received. RESULTS: This series included 15 Category A and 55 Category B patients. Most patients were non-US contractors with one chronic condition. Most patients received medical treatments in accordance with Department of Defense Practice Management Guidelines. For Category A patients, mechanical ventilation use declined from a mean average of 10.67 days to 2.83 days following the introduction of high-flow nasal cannula. Average hospital length of stay was 6 days (range 2-23). One death occurred in a patient greater than 60 years old with three known prior medical conditions. Most patients were discharged to a non-medical isolation facility. Aeromedically evacuated patients were mostly US military and US contractors. CONCLUSION: We faced several challenges including retrofitting a Role 3 facility designed for trauma care for management of a highly contagious respiratory viral illness. Logistics constraints impacted timely delivery of medical therapies and equipment and decreased efficiency of aeromedical evacuation. Despite these challenges and the simultaneous trauma mission, most patients received medical care in accordance with treatment guidelines with a low mortality rate.

Adjuvant endocrine therapy is associated with improved overall survival in elderly hormone receptor-positive breast cancer patients.

PURPOSE: There is controversy regarding the survival benefit of endocrine therapy (ET) in elderly patients with early invasive hormone receptor-positive (HR+) breast cancer. In this study, we characterize a single institution's practice patterns using adjuvant ET for these patients and evaluated the effect of ET on outcomes. METHODS: A review of a prospectively maintained database identified 483 women ≥ 70 years old who underwent breast -conserving surgery (BCS) for stage I-III HR+ tumors from 2004-2013. We compared clinicopathologic characteristics, overall survival (OS), disease-free survival (DFS), locoregional recurrence (LRR), and breast cancer-specific survival (BCSS) in patients who did and did not receive ET. RESULTS: Compared to patients who did not get ET, patients who received ET were younger (median age 76 vs 78 years, p = 0.006), had larger tumors (median size 15 vs 14 mm, p = 0.016), underwent sentinel lymph node (LN) biopsy (83.7 vs 67.8%, p < 0.001), had positive LNs (25.5 vs 9.8%, p = 0.008), and received radiation (XRT, 76 vs 43%, p < 0.001). After adjusting for ASA score, age, LN status, tumor grade, and XRT, receipt of ET was associated with improved OS (HR 0.44; 95% CI 0.25-0.77; p = 0.004) and DFS (HR 0.42; 95% CI 0.28-0.64; p < 0.01). Receipt of ET was associated with improved LRR on univariate analysis (HR 0.25; 95% CI 0.09-0.70; p = 0.008); however, after adjusting for grade and XRT, this was not statistically significant on multivariable analysis (HR 0.38; 95% CI 0.13-1.08; p = 0.069) and was not associated with BCSS (HR 0.59; 95% CI 0.16-2.16; p = 0.43). CONCLUSIONS: ET was associated with significant improvements in OS and DFS, regardless of clinicopathological features; however, receipt of ET did not impact LRR and BCSS.

Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade.

Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a noninflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated with improved survival of the mice. To translate these findings into a clinical setting, 26 patients with advanced melanoma were treated locally by isolated limb infusion with the nitrogen mustard alkylating agent melphalan followed by systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II trial. This combination of local chemotherapy with systemic checkpoint blockade inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23% partial response rate) and a 58% progression-free survival at 1 year. The clinical response was associated with increased T-cell infiltration, similar to that seen in the murine models. Together, our findings suggest that local chemotherapy combined with checkpoint blockade-based immunotherapy results in a durable response to cancer therapy. Cancer Immunol Res; 6(2); 189-200. ©2018 AACR.