Dr Shameem on Clinical Trial and Chemo Considerations in Frontline Pancreatic Cancer

“In the frontline setting, I always discuss clinical trial options with my patients. At my institution, we do have trials available, but KRAS inhibitor trials in particular are not always easy to access. Some patients are willing to travel for a clinical trial, and others prefer to remain close to home and pursue standard-of-care therapy.”

Raji Shameem, MD, a medical oncologist and hematologist at Orlando Health Cancer Institute, discussed the balance between clinical trial enrollment and utilizing standard-of-care chemotherapy regimens in first-line treatment planning for patients with metastatic pancreatic adenocarcinoma.

Shameem began by noting that first-line treatment planning for patients with advanced pancreatic cancer should routinely include a structured discussion of clinical trial eligibility, alongside standard chemotherapy options. In his practice, he frames clinical trials as an early consideration rather than a last resort, while acknowledging that feasibility often dictates whether enrollment is realistic. Although investigational approaches, particularly with targeted therapies such as KRAS inhibitors, may be attractive given the high prevalence of KRAS alterations in pancreatic cancer, he noted that access to these trials can be limited by site availability and eligibility constraints. Additionally, some patients may be willing travel to participate in clinical trials, whereas others prioritize remaining close to home and receiving stardard-of-care chemotherapy

Shameem highlighted that the importance of clinical trials becomes even more pronounced after progression on first-line therapy, when evidence-based options narrow. He described the second-line setting as a key inflection point: patients who progress on intensive fluoropyrimidine-based regimens such as NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil [5-FU], and leucovorin) or modified FOLFIRINOX (leucovorin, 5-FU, irinotecan, and oxaliplatin) often have few alternatives beyond gemcitabine-based therapy, and outcomes remain suboptimal, Shameem said. In this context, if a patient maintains adequate performance status and organ function, and a biologically relevant study is available, he strongly considers referral or enrollment because trial participation may offer access to novel mechanisms of action not otherwise available in routine practice. For patients who receive frontline gemcitabine-based therapy and subsequently experience disease progression, he pointed to liposomal irinotecan–based therapy (NALIRI) as an evidence-supported second-line option.

At the same time, Shameem underscored that standard-of-care chemotherapy remains foundational in the frontline setting and must be individualized based on patient goals, functional status, comorbidities, and anticipated tolerability. He noted that, despite approximately 80% of patients harboring KRAS mutations, a meaningful subset does not; therefore, treatment cannot rely on any single biomarker-driven paradigm.