Metastasis-directed therapy shows favorable results in treating oligometastatic prostate cancer (Abstract 15)
While targeted therapy and systemic treatments, such as hormonal therapy, are the standard of care for patients with oligometastatic prostate cancer (omPC), researchers now are studying the effects of metastasis-directed therapy, which targets metastatic sites through localized surgery or radiation therapy. Phase II trials using metastasis-directed therapy in patients with omPC, representing a small number of cohorts, have shown improved progression-free survival (PFS) but have been less successful in improving other response biomarkers. Therefore, researchers led by Chad Tang, M.D., analyzed a data subset of 472 patients with omPC from the X-Met consortium, focusing on five randomized clinical trials. For the first time, they demonstrated positive activity in radiographic PFS and castration-resistance free survival in these patients. The results also showed that metastasis-directed therapy achieved an overall survival rate of 92% after three years compared to 86% in those receiving standard-of-care treatment. These results highlight the therapeutic potential of metastasis-directed therapy for these patients. Tang will present the findings Feb.13.
Antibody-drug conjugate is safe and effective in patients with advanced urothelial cancer (Abstract 663)
Patients with advanced/metastatic urothelial cancer have poor prognoses and limited treatment options, often resulting in low five-year survival rates. Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate (ADC) targeting TROP2, a surface protein highly expressed in urothelial bladder cancer that is being tested in various solid tumors. In updated results from the ongoing Phase I TROPION-PanTumor01 trial, Funda Meric-Bernstam, M.D., and colleagues report that Dato-DXd exhibited promising antitumor activity with a manageable safety profile in 40 patients with urothelial cancer. The treatment resulted in an objective response rate of 25% with no unexpected side effects. Dato-Dxd currently is being investigated further in Phase I/II trials. Meric-Bernstam will present the findings Feb.14.
General public and health care professionals view personalized risk-based cancer screening as a helpful tool
Personalized risk assessments (PRAs) based on factors like age, sex or smoking history can help reduce cancer deaths, but they often use a one-size-fits-all approach. These PRAs may miss individual differences in risk and lead to over- or under-screening, unnecessary treatments or false positives, prompting a shift toward more personalized risk-based screening (PRBS). Through a systematic review with meta-analysis of 63 studies from January 2010 to April 2024, researchers led by Iakovos Toumazis, Ph.D., examined the perceptions of PRAs/PRBS among the general public and health care professionals. The results showed that 78% of the public and 86% of health care professionals view PRBS positively, and both groups agree that personalized screening is a smart step to improving care and reducing cancer deaths. However, challenges at the individual, professional and system levels must be resolved before PRBS can become part of routine practice. Learn more in The Lancet Public Health.
CD38 expression promotes metastasis in triple-negative breast cancer
Triple-negative breast cancer (TNBC) is a highly metastatic cancer with limited treatment options, highlighting a need for new therapeutic targets. In a study led by Tanvi Visal, Ph.D., and George Calin, M.D., Ph.D., researchers investigated how TNBC becomes metastatic – a process known as the metastatic cascade – and identified the CD38 protein as a potential interventional target. During the metastatic cascade, cells undergo epithelial to mesenchymal transition, but not all cells fully complete this transition, resulting in hybrid cancer cells with high CD38 expression and metastatic potential. The researchers discovered that disrupting CD38 expression impacted the ability of these cells to create an immunosuppressive microenvironment. Additionally, targeting CD38 and PD-L1, whose expression correlates with CD38, improved anti-tumor responses and reduced tumor growth in preclinical models. These results underscore the role of CD38 in TNBC metastasis and progression as well as its therapeutic potential. Learn more in Cancer Research.
Novel combination shows promise for patients with advanced solid tumors
Immune checkpoint inhibitors (ICIs) are effective for many cancer types, but some patients develop treatment resistance partly due to limited T cell infiltration into advanced solid tumors. Studies have shown that targeting the NLRP3 pathway can improve T cell tumor infiltration by releasing interleukins, which act as messengers between white blood cells and the body’s cells. In a first-in-human Phase I trial, researchers led by Sarina Piha-Paul, M.D., investigated the safety and efficacy of intratumoral delivery of BMS-986299 – an NLRP3 activator – as a monotherapy or in combination with ICIs in 36 patients with breast, colorectal and head and neck cancers, and other solid tumors. The monotherapy increased CD8+ T cell infiltration but showed no antitumor activity. In nine patients who received the combination therapy, the objective response rate (ORR) was 33%. These preliminary results suggest that BMS-986299 is safe and has promising effects when added to other immunotherapy approaches, meriting further investigation. Learn more in the Journal for ImmunoTherapy of Cancer.
Study shows importance of reevaluating HER2 status in breast cancer patients following T-DXd treatment
Trastuzumab deruxtecan (T-DXd) is a targeted therapy currently approved for patients with metastatic HER2-positive or HER2-low breast cancer, but its impacts on HER2 status following treatment are not fully understood. In a new study led by Funda Meric-Bernstam, M.D., researchers retrospectively evaluated 41 patients with metastatic breast cancer treated with T-DXd. They found that 11 patients (32.4%) lost HER2 expression following treatment with T-DXd, while another 10 (29.4%) had decreased HER2 expression. Overall, the loss and decrease of HER2 expression was more substantial among the subgroup of patients who had been previously treated with cyclin dependent kinase (CDK) inhibitors. Notably, there was no significant survival difference between patients who experienced HER2 loss and those who did not. Further study is needed to understand the mechanisms behind the HER2 loss, but these findings highlight the importance of reevaluating HER2 status before treating patients with additional HER2-targeted therapies. Learn more in Clinical Cancer Research.
BRAF targeted therapy is effective for BRAF-mutant appendix cancer
Appendiceal adenocarcinomas (AA) – rare tumors in the appendix – have limited treatment options, and oncologists have little data to guide treatment selection. Historically, AA is treated with the same chemotherapy used for colorectal cancer (CRC), although there is little data to suggest this benefits patients. To provide further insights, researchers led by John Paul Shen, M.D., retrospectively compared the molecular profiles and clinical characteristics of tumor samples from patients with BRAF-mutant AA and BRAF-mutant CRC. While AA typically spreads to the lining of the abdomen, CRC usually spreads to the liver or lungs. BRAF mutations were associated with particularly poor prognoses in CRC, but this was not the case in AA. Additionally, BRAF mutations in CRC were associated with female sex, mucinous histology and a higher grade, whereas these relationships were not found in AA. The study identified, for the first time, that BRAF-mutant AA responds to BRAF targeted therapy, with an 80% disease control rate and a median progression-free survival (PFS) of 7.1 months, which is superior to traditional chemotherapy in these patients. The findings highlight a promising therapeutic strategy for this rare patient population. Learn more in npj Precision Oncology.
Blocking autophagy could enhance efficacy of CDK inhibitors in metastatic breast cancer
Standard treatment for patients with ER+/HER2- metastatic breast cancer includes endocrine therapy with the CDK4/6 inhibitors palbociclib and letrozole, but many develop treatment resistance. Previous studies showed that adding hydroxychloroquine (HCQ) – an autophagy inhibitor blocking cellular degradation – improved outcomes in preclinical models treated with low palbociclib doses. In a Phase I trial, Khandan Keyomarsi, Ph.D., Debasish Tripathy, M.D., and colleagues evaluated the safety and efficacy of adding HCQ to the standard treatment in 14 patients with ER+/HER2- metastatic breast cancer. Two patients achieved partial responses with significant tumor shrinkage, and 11 patients experienced stable disease without tumor progression. Biomarker analysis revealed responders had elevated levels of markers associated with autophagy inhibition, supporting HCQ’s mechanistic action. These findings suggest that autophagy inhibition could enhance the efficacy of CDK4/6 inhibitors in these patients, potentially overcoming resistance. Further validation in a Phase II trial is planned. Learn more in npj Breast Cancer.
Survey aims to standardize nursing knowledge and learning modalities in cardio-oncology
With improved cancer outcomes, cardiovascular disease is now on par with recurrent cancer or secondary malignancies as the cause of death in some cancer types. Providing optimal cardio-oncology care requires a multidisciplinary team comprising expert oncology and cardiovascular providers, including educated nurses participating in patient assessment. Yet the field currently lacks a nursing knowledge standard. To establish the educational needs of nurses in cardio-oncology, Anecita Fadol, Ph.D., and colleagues conducted an international cross-sectional survey addressing 23 questions related to demographics, educational characteristics, clinical practice settings, cardio-oncology learning content and preferred methods of delivery. Of the 329 responses, the majority of nurses were interested in learning via pre-recorded webinars or live virtual meetings, while many expressed interest in cancer therapeutics and management of specific cardiovascular toxicities. The researchers concluded that an accessible, asynchronous cardio-oncology core curriculum may help expand education in this new field, ultimately benefiting cancer patients worldwide. Learn more in Cardio-Oncology.
Awards and Honors
Emil J Freireich, M.D., has been posthumously inducted into the 2025 Class of the National Inventors Hall of Fame for developing the first continuous-flow blood cell separator David Gershenson, M.D., professor of Gynecologic Oncology and Reproductive Medicine, was awarded the 2024 Rosalind Franklin Prize for Excellence in Ovarian Cancer Research by the Ovarian Cancer Research Alliance In case you missed it
Read below to catch up on recent MD Anderson press releases.
Combination of dual-targeted therapies and chemotherapy shows high response rates in BRAF-mutated metastatic colorectal cancer Read this press release in the MD Anderson Newsroom.
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