Dr King on the Need for Less-Toxic Therapies in Advanced Gastrointestinal Cancers

Daniel King, MD, PhD, assistant professor, Institute of Cancer Research, Feinstein Institutes for Medical Research, Northwell Health, assistant professor, Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, discusses the current treatment landscape and the need to develop therapies with few toxicities in advanced gastrointestinal cancers, including esophageal, pancreatic, and colon cancer.

King emphasizes the significant toxicity associated with the existing regimens. Even when comparing currently available regimens for the treatment of an individual patient, this evaluation often involves treatment paths using different toxic agents, he says.

King underscores the importance of developing treatment protocols that maintain efficacy and are associated with reduced toxicity, he says. The current standard of care often involves highly toxic regimens, which can significantly impact the patient's quality of life. As a result, there is a critical need for advancements in therapeutic approaches that mitigate these adverse effects, he continues.

King points to the pancreatic cancer space as one example of an avenue for improved treatment without increased toxicity. He explains that the emergence of KRAS inhibitors is promising because these inhibitors have shown efficacy without inducing additional toxicity in patients. This could represent a notable advancement, given the historically limited therapeutic options for pancreatic cancer, which is often associated with poor prognosis and high resistance to conventional therapies.

Given the limited toxicity observed thus far with KRAS inhibitors, the emergence of these agents could open up potential combination therapies for patients with pancreatic cancer, King continues. By integrating KRAS inhibitors with existing chemotherapy regimens, there is a possibility of enhancing therapeutic outcomes without exacerbating toxicity.

King's insights highlight the critical need for ongoing research and development in the field of oncology to create more effective and less toxic treatment regimens for patients with advanced GI cancers. In the pancreatic cancer space specifically, the emergence of KRAS inhibitors could bring a targeted therapy approach to the treatment paradigm.

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Daniel King, MD, PhD, discusses the need to develop less-toxic regimens for advanced gastrointestinal cancers.

Daniel King, MD, PhD, assistant professor, Institute of Cancer Research, Feinstein Institutes for Medical Research, Northwell Health, assistant professor, Department of Internal Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health, discusses socioeconomic disparities causing delays in germline genetic testing for patients with pancreatic cancer.

At Northwell Health, only 36% of patients with pancreatic adenocarcinoma obtained germline genetic testing, despite ASCO guidelines recommending germline testing for patients diagnosed with the disease, as well as first-degree relatives. Barriers to germline genetic testing may be related to several socioeconomic factors, King says.

King and colleagues completed a large-chart review at Northwell Health, gathering data on patients with pancreatic adenocarcinoma to examine information on location, race, ethnicity, insurance, primary language, and social work. The study identified 305 patients with pancreatic adenocarcinoma from between March 2016 to February 2022, and mutation reports were available for 103 patients. Investigators also looked at the time difference between when patients were diagnosed and when germline testing was conducted, King says.

Findings presented at the 2023 Gastrointestinal Cancers Symposium showed that there was a significant disparity when comparing the time needed to conduct germline testing. Patients who were African American or were of lower socioeconomic classes experienced a much longer delay in germline testing. The investigation also identified other associations with delay in germline testing, including high social work needs, the need for transportation, and patients with less social contact. Although investigators attempted to explore other factors that could explain these disparities, it was difficult to identify causative effects, King notes.

These disparities are important to address because results from germline testing can help determine first-line chemotherapy options, King adds. For example, patients with 

 mutations tend to have improved responses to platinum-based chemotherapy. Detecting this mutation through testing can allow faster delivery of a beneficial treatment option, King continues. Additionally, the results of a patient’s germline testing can have implications for immediate family members, who may require cascade testing, King says.

Identifying causative factors is needed to help close the gap in this disparity, and a multidisciplinary collaboration is needed to help expedite germline testing for patients with pancreatic cancer, King concludes.

Daniel King, MD, PhD, discusses socioeconomic disparities causing delays in germline genetic testing for patients with pancreatic cancer.

Daniel King, MD, PhD

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Dr King on the Need for Less-Toxic Therapies in Advanced Gastrointestinal Cancers

Dr. King on Delays in Access to Germline Testing in Pancreatic Cancer