Fred Hutch at ASCO: Progress in treating metastatic cancer, hospice access for cancer patients, use of machine learning with CAR T-cell therapy

(Press-News.org) The 2024 annual meeting of the American Society of Clinical Oncology (ASCO) will take place in Chicago and online May 31-June 4.  

Below are highlights of Fred Hutch Cancer Center research to be presented at the conference and experts available to comment on news. You can follow Fred Hutch on social media for additional updates and check out Fred Hutch booth #14018 in the exhibit hall. 

For interview requests with Fred Hutch experts, please contact media@fredhutch.org.   

 

Prostate cancer 

Prostate cancer is the most common cancer among men in the United States and, according to the National Cancer Institute, approximately 20% of cases are castration resistant. Metastatic castration-resistant prostate cancer (mCRPC) is an advanced type of prostate cancer that has spread beyond the prostate gland and no longer responds to hormone treatment. Three Fred Hutch abstracts examine the disease, potential advanced treatments and the affects certain therapies have on these patients.  

Researcher Jessica Hawley, MD, MS, is presenting her investigator-initiated Phase II study testing clinical activity of tumor necrosis factor (TNF–a) inhibitors in combination with androgen receptor inhibitors in treating patients with CRPC.  

In an oral presentation, Michael Schweizer, MD, who is the lead investigator, will share results of a Phase I/II study that shows the combination therapy of mevrometostat and enzalumatide plus androgen deprivation therapy demonstrates a manageable safety profile in treating patients with CRPC.  

In a retrospective cohort study presented by Alireza Ghodsi, MD, postdoctoral research fellow, found that 20% of mCRPC patients treated with a novel theranostic therapy, Lutetium-177 PSMA, experienced grade 3 or higher hematologic adverse events, and elevated risk was observed in patients who had higher PSMA PET bone volume of disease. 

 

Non-small cell lung cancer 

Lung cancer is the second most common cancer in men and women in the U.S. Approximately 85% of all cases are categorized as non-small cell lung cancer (NSCLC) – a less aggressive lung cancer. This year, Fred Hutch research explores advancing treatments and improving outcomes for NSCLC patients.  

Natalie Miller, MD, PhD, a fellow at Fred Hutch and UW Medicine, will present findings that suggest Napsin A TCR frequency may be used as a non-invasive biomarker for lung cancer patients. The study, which sequenced cells from metastatic NSCLC patients who received an anti PD-1 or checkpoint inhibitor alone or in combination, found that patients had better overall survival outcomes if a higher frequency of Napsin A TCR, a new marker for lung cancer or clonotype, was present.  

 

Access to care and clinical trials 

With the increase in new tools to diagnose, treat and prevent cancer, it’s critical that all patients can access these advances. The following abstracts build our understanding of where disparities exist and how we can improve participation in cancer clinical trials. 

In a national cohort of nearly 15,000 prostate cancer patients, Hiba Khan, MD, MPH, linked germline genetic testing results with insurance claims to determine associations with personal and family history, disease stage, region of the U.S. and race. Among noteworthy findings, Khan reports that three quarters of people with a pathogenic genetic variant did not have claims for family history, highlighting the importance of genetic testing in all patients who meet testing criteria. 

In an analysis of 18 Phase II and III SWOG Cancer Research Network clinical trials, Joseph Unger, PhD, MS, and collaborators found higher levels of patient-reported fatigue predicted increased risk of adverse events. These results suggest that patient-reported fatigue may be an important way to determine toxicity risk and could help select the most appropriate treatment. Additionally, Unger chaired a joint task force of ASCO and the Friends of Cancer Research to take a deeper look at trial mitigation strategies during the COVID pandemic. Together they found that more flexible procedures, such as allowing for use of telemedicine and remote monitoring, did not result in long-term reduction in data quality and may be a strategy to increase clinical trial participation in the future. 

Lauren Shih, MD, compared end-of-life experiences among patients in Washington state with head and neck squamous cell carcinoma (HNSCC) to those of patients with other solid tumors. She found a greater proportion of HNSCC patients were insured by Medicaid at end of life and were less likely to enroll in hospice prior to death, which could mean they are not accessing hospice services that they might benefit from. 

By linking patient-level credit records with cancer and claims data, Chris Su, MD, MPH, identified a disparity among multiple myeloma patients experiencing financial fragility. The study found that financial fragility is strongly associated with suboptimal treatment patterns in multiple myeloma patients, who typically face higher out-of-pocket costs for their medications. 

 

Rare cancers 

Researching rare cancers often requires creative methods to include a large enough study size from which to draw conclusions. These abstracts reflect diligent efforts to assess adverse events when using a checkpoint inhibitor in patients with rare cancers and to enroll people with neuroendocrine carcinomas in a clinical trial combining an immunotherapy drug with the standard treatment regimen. 

Megan Othus, PhD, led an analysis of whether side effects called immune-related adverse events in patients with rare cancers treated with checkpoint inhibitors could predict the likely course or outcome of the disease. Drawing on data from a large federally funded national clinical trial led by the SWOG Cancer Research Network, Othus and team found that lower grades of immune-related adverse events during the first cycle of treatment correlated with better outcomes in this patient population compared to no adverse events, while higher grade adverse events correlated with worse outcomes compared to no adverse events. 

Neuroendocrine carcinomas (NEC) are rare and aggressive cancers that arise from neuroendocrine cells. Often, NEC are diagnosed in the lungs, but they also develop in other parts of the body, such as the gastrointestinal, genitourinary and gynecological tracts. Current treatments for NEC in the lungs are also used to treat extrapulmonary NEC, but whether such treatments have similar benefit is unclear. Additionally, biomarkers are needed to help identify patients with NEC who are more likely to response to certain treatments. David Zhen, MD, is leading a Phase II/III National Cancer Institute-sponsored trial through the SWOG Cancer Research Network to evaluate the efficacy of adding atezolizumab to chemotherapy for patients with extrapulmonary NEC and identifying associated biomarkers of response. 

 

Breast cancer  

According to the Breast Cancer Research Foundation, nearly 30% of people diagnosed with early-stage breast cancer develop metastatic disease. While early detection of breast cancer is allowing women with metastatic disease to live longer, their need for new therapies due to non-responsiveness to treatment means more research must be done to advance treatments for these patients. 

Sara Hurvitz, MD, MPH, and senior vice president and director of clinical research at Fred Hutch, will present a Phase III clinical trial design that will evaluate the overall survival of metastatic breast cancer patients who are treated with a combination therapy of an off-the-shelf targeted cellular immunotherapy and a checkpoint inhibitor versus a treatment chosen by the clinician with no approved alternative therapies available.  

 

Gynecological cancers 

Cervical cancer is the leading cause of cancer-related mortality in low- and middle-income countries. Desmoid tumors, which are growths in the abdomen and considered non-cancerous, can have significant impacts on patients’ quality of life and be difficult to diagnose. Two Fred Hutch abstracts explored issues related to these diseases with the goal of informing better intervention strategies and improving quality of life for women facing these diseases. 

Daniel Olivieri, MD, MPA, analyzed surveys from 48,055 women in five sub-Saharan African nations and found that age, education and wealth were associated with increased cervical cancer awareness, while living in rural locations and experiencing emotional abuse were associated with decreased cervical cancer awareness. Of the women surveyed, only 3% had been screened for cervical cancer. 

Elizabeth Loggers, MD, PhD, and sarcoma expert, monitored the ovarian toxicity in females of reproductive potential enrolled in the Phase III DeFi study. The research found that the trial design aligned with current guidelines and supported the use of both clinical measures and hormone biomarkers in oncology clinical studies.  

 

Hematologic malignancies 

Since the 1970s, Fred Hutch has been a leader in treating blood cancers. The following abstracts explore strategies to improve outcomes in patients with chronic lymphocytic leukemia (CLL), detect neurotoxicities in patients who were treated by CAR T-cell therapy and identify patients who are higher risk of hematoxicity following treatment. 

Mazyar Shadman, MD, MPH an associate professor and Innovators Network Endowed Chair at Fred Hutch is the global co-chair for the Celestial trial, an ongoing, open label, multi-regional Phase III study of a combination therapy for patients who have not yet been treated for this disease. In another abstract, Dr. Shadman is presenting results from a network meta-analysis evaluating the available treatments for CLL. The analysis found a statistically significant improvement in PFS for Zanubrutinib compared to other approved inhibitors of bruton tyrosine kinase. 

Jennifer Huang, MD, PhD, assessed a machine learning algorithm in predicting severe immune effector cell-associated neurotoxicity syndrome, a complication leading to morbidity and mortality in patients receiving CAR T-cell therapy. Huang and team plan to develop a user-friendly web application of this tool. In another study, Huang followed Fred Hutch patients with a rare blood cancer called mixed phenotype acute leukemia and found that those who received hematopoietic stem cell transplants had significantly improved survival rates. Additionally, patients who were not in remission also may benefit from transplant. 

Hematotoxicity, or the adverse effect of a drug or agent on blood or bone marrow, is a major cause of morbidity following CAR T-cell therapy. Emily Liang, MD, developed a statistical model in patients with blood cancers undergoing CAR T-cell therapy based on pre- and post-infusion factors to predict whether a patient will experience higher levels of hematotoxicity. In a related study, Liang compared two systems for identifying CAR T-cell therapy recipients at higher risk of hematotoxicity and found that a new machine-learning method was more effective at predicting overall survival than a more commonly used predictive tool. 

 

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Note: To the extent any commercializable discoveries result from the aforementioned research, Fred Hutch and the scientists who contributed to the discoveries may stand to benefit from their future commercialization. 

 

The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary and encouraging results from early-stage clinical trials may not be supported in later-stage clinical trials.  No conclusions should be drawn from the information in this Tip Sheet or from the conference presentations about the safety, efficacy or likelihood of regulatory approval of these investigational products and/or therapies.  

 

Fred Hutch does not endorse or verify the accuracy of any content of any third-party sites, materials or related information that may be referenced by the presentations. 

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Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options while accelerating discoveries that prevent, treat and cure cancer and infectious diseases worldwide. 
 

Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, immunotherapy, HIV/AIDS prevention and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services. Fred Hutch also serves as UW Medicine’s cancer program. 

 

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