Dr Lim on Multidisciplinary Approaches to Pancreatic Cancer Management

Kian-Huat Lim, MD, PhD, medical oncologist, associate professor, medicine, Division of Medical Oncology, Siteman Cancer Center, the Washington University School of Medicine, 

discusses the importance of multidisciplinary collaboration

 when diagnosing and treating patients with pancreatic cancer.

For patients with unresectable pancreatic tumors, the treatment journey often begins with several months of chemotherapy, Lim begins. During this time, consulting with radiation oncologists is necessary to determine whether radiation therapy may control localized disease, he explains. However, only a small fraction of patients can tolerate this intense treatment for month on end due to chemotherapy-related toxicities. Lim says that patients may require a break from chemotherapy due to fatigue and the physical toll it takes on their bodies. In these circumstances, radiation therapy can be a valuable option for managing local disease and allowing patients to temporarily stop chemotherapy treatment, he notes.

In addition to radiation oncologists, oncologists will often collaborate with gastroenterologists, Lim expands. Patients with tumors located in the head or body of the pancreas often suffer from obstructive jaundice. To address this, gastroenterologists can perform a biliary stent placement to keep the bile ducts open. This ensures that the patients can continue receiving treatment without additional complications from jaundice, he elucidates.

As pancreatic cancer is a multifaceted disease with associated issues such as diabetes, it is crucial to have endocrinologists involved in the care team. Moreover, pain management is a significant concern for many patients. Pain specialists often play a vital role in addressing severe and chronic pain issues, Lim reports.

Lastly, psychological support is indispensable for both patients and their families, he continues. At Siteman Cancer Center, as well as other major cancer centers, psychologists and palliative care specialists are integral members of the care team. Providing comprehensive support options is essential to help patients and their families navigate this challenging journey, Lim concludes.

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Kian-Huat Lim, MD, PhD, discusses the importance of multidisciplinary collaboration when diagnosing and treating patients with pancreatic cancer.

Dr Lim on the Treatment of Resectable and Borderline Resectable Pancreatic Cancer

Kian-Huat Lim, MD, PhD, medical oncologist, associate professor, medicine, Division of Medical Oncology, Siteman Cancer Center, the Washington University School of Medicine, discusses the current standard of care (SOC) for patients with resectable or borderline resectable pancreatic cancer.

The current SOC for patients with resectable or borderline resectable pancreatic cancer involves incorporating tumor markers and neoadjuvant chemotherapy to optimize outcomes, Lim begins. For patients with localized and seemingly resectable pancreatic cancer, one of the primary considerations is the level of tumor markers, particularly CA19-9, he explains. In such cases, neoadjuvant chemotherapy is typically administered to address these potential micrometastases before proceeding with surgery, Lim adds.

When treating patients who have borderline resectable or locally advanced pancreatic cancer, neoadjuvant chemotherapy becomes even more critical, he continues, adding that downstaging the tumor, making it more amenable to surgical resection, is the goal. This treatment phase usually spans between 4 and 6 months, Lim emphasizes.

A 2022 trial compared 2 chemotherapy regimens—FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel—as first-line treatments for patients with localized pancreatic ductal adenocarcinoma, he expands. The study found that FOLFIRINOX resulted in higher response rates, establishing it as the preferred regimen for downstaging disease in patients who are able to sufficiently handle its effects. However, it is essential to note that both regimens are associated with unique toxicities, necessitating careful patient selection, Lim explains.

In clinical practice, FOLFIRINOX or NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil, and leucovorin) is often chosen for patients with locally advanced disease who are potential candidates for surgery, according to Lim. The choice between these regimens is still a matter of clinical judgment, as there is no definitive evidence favoring one over the other, Lim explains. The medical community recognizes the need for a prospective study to directly compare FOLFIRINOX with NALIRIFOX to determine the optimal choice for these patients, Lim notes. Until such data are available, oncologists will continue to rely on existing evidence and their clinical expertise to guide treatment decisions for patients with pancreatic cancer, he concludes.

Kian-Huat Lim, MD, PhD, discusses the current standard of care for patients with resectable or borderline resectable pancreatic cancer.

Dr Lim on Treatment With FOLFIRINOX vs NALIRIFOX in Metastatic Pancreatic Cancer

Kian-Huat Lim, MD, PhD, medical oncologist, associate professor, medicine, Division of Medical Oncology, Siteman Cancer Center, the Washington University School of Medicine, discusses what factors influence the choice between treatment with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil, and leucovorin) for patients with metastatic pancreatic cancer.

The distinction between NALIRIFOX and FOLFIRINOX lies primarily in the formulation of irinotecan used within the regimen. NALIRIFOX replaces the standard free form of irinotecan found in FOLFIRINOX with liposomal irinotecan, which has a longer retention time within tissues, Lim begins. Patient selection plays a critical role in determining the suitability of NALIRIFOX vs FOLFIRINOX due to differences in their toxicity profiles, he explains, adding that NALIRIFOX is associated with slightly higher incidences of nausea, vomiting, and diarrhea compared with FOLFIRINOX. Consequently, in patients prone to experiencing these adverse effects (AEs), careful consideration is needed to mitigate potential exacerbation of these toxicities, Lim notes.

One of the notable advantages of NALIRIFOX is its reduced reliance on oxaliplatin, a component known for causing neuropathy, Lim expands. By using a lower dose of oxaliplatin compared with FOLFIRINOX, NALIRIFOX may be better suited for patients with pre-existing neuropathy, those with long-term diabetes, or elderly patients who are more susceptible to neuropathic AEs, he reports. Furthermore, the decreased dose of oxaliplatin in NALIRIFOX contributes to less severe bone marrow suppression compared with FOLFIRINOX, a consideration that is particularly important in patients with compromised bone marrow function, Lim states.

Despite these nuances in toxicity and dosing, the overall outcomes with NALIRIFOX and FOLFIRINOX are comparable, he continues. Both regimens demonstrate similar overall survival rates. However, NALIRIFOX may exhibit a higher response rate, particularly in patients with locally advanced or borderline resectable disease where tumor downstaging is a critical therapeutic goal, Lim states. 

The higher response rates seen with NALIRIFOX raise questions about this regimen’s potential efficacy in downstaging tumors for surgical intervention in patients with locally advanced or borderline resectable disease, according to Lim. Further studies are needed to validate these findings and determine the regimen’s suitability in specific clinical scenarios, he concludes.

Kian-Huat Lim, MD, PhD, discusses factors influencing the choice between treatment with FOLFIRINOX or NALIRIFOX for metastatic pancreatic cancer.

Dr Lim on the Current Treatment Paradigm For Metastatic Pancreatic Cancer

Kian-Huat Lim, MD, PhD, medical oncologist, associate professor, medicine, Division of Medical Oncology, Siteman Cancer Center, the Washington University School of Medicine, discusses the current treatment options for patients with metastatic pancreatic cancer.

, systemic combination chemotherapy remains the primary treatment approach in both the first- and second-line pancreatic cancer settings, Lim says. Limited progress has been made regarding targeted therapies and immunotherapies for this disease, although promising data are emerging with KRAS inhibitors and certain immunotherapy combinations, which are still in early stages of study, according to Lim. For now, chemotherapy remains the cornerstone of treatment, with FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel (Abraxane) being the predominant regimens, he explains

A newer addition to the treatment armamentarium is NALIRIFOX (nanoliposomal irinotecan [Onivyde], 5-fluorouracil, leucovorin, and oxaliplatin), which has gained FDA approval and is now included in the National Comprehensive Cancer Network guidelines for pancreatic adenocarcinomaas an alternative first-line therapy for locally advanced or metastatic disease, Lim expands. NALIRIFOX closely resembles FOLFIRINOX in terms of efficacy and survival benefits but offers a distinct toxicity profile, he reports. Notably, NALIRIFOX is associated with more gastrointestinal adverse effects, such as diarrhea, but exhibits less neuropathy and bone marrow suppression compared with FOLFIRINOX, Lim elucidates, saying that these AE profile differences are crucial considerations for oncologists when selecting between the 2 regimens for individual patients.

The key distinction between NALIRIFOX and FOLFIRINOX lies in the replacement of free irinotecan with liposomal irinotecan in the NALIRIFOX regimen, he continues. Liposomal irinotecan has a prolonged tissue retention time, potentially resulting in sustained antitumor effects, according to Lim. Lim acknowledged that progress in developing novel therapies for metastatic pancreatic cancer has been slower compared with that in other malignancies. However, there is optimism for the future with the anticipation of more innovative treatment approaches on the horizon, he explains. Despite the current reliance on chemotherapy, ongoing research efforts, particularly in the realms of targeted therapies and immunotherapies, offer hope for improved outcomes and expanded treatment options for patients with metastatic pancreatic cancer in the coming years, Lim concludes.

Kian-Huat Lim, MD, PhD, discusses the current treatment options for patients with metastatic pancreatic cancer.

Kian-Huat Lim, MD, PhD

Articles

Dr Lim on Multidisciplinary Approaches to Pancreatic Cancer Management

Dr Lim on the Treatment of Resectable and Borderline Resectable Pancreatic Cancer

Dr Lim on Treatment With FOLFIRINOX vs NALIRIFOX in Metastatic Pancreatic Cancer

Dr Lim on the Current Treatment Paradigm For Metastatic Pancreatic Cancer