Pharmacists Can Help Address Treatment Challenges for Patients With Cholangiocarcinoma

The symptoms for cholangiocarcinoma are not easy to detect until the disease progresses, explained Sal Bottiglieri, PharmD, BCOP, clinical pharmacy coordinator of medical oncology at Moffitt Cancer Center, Tampa, Florida, during a Pharmacy Times clinical forum discussion. Because cholangiocarcinoma is often identified in patients during later stages of the disease, there can be difficulties that arise as a result during treatment.

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Bottiglieri explained further that in early disease, it is common for patients to receive a diagnosis when getting a CT scan for another reason, with the diagnosis coming from an incidental finding. “There are differences in symptoms [between] intrahepatic and extrahepatic cholangiocarcinomas too,” Bottiglieri said during the forum. “So intrahepatic cholangiocarcinoma usually [presents] vague symptoms, [such as] fever, weight loss, abdominal pain. Extrahepatic, you usually think of more of a jaundice picture, because [patients are] going to have more of the biliary obstruction and the common hepatic duct.”

Further, Bottiglieri noted that there are differences in genetic panels between intrahepatic and extrahepatic cholangiocarcinomas that may influence physicians’ decision-making when determining appropriate treatment for patients. Avani Yenamandra, MD, clinical pharmacy specialist at MD Anderson Cancer Center at Cooper, Camden, New Jersey, explained that she uses genetic paneling as a method of eliminating treatment options. As an example, she noted that there are many drugs that can target FGFR mutations. FGFR2 alterations, which are present in approximately 10% to 15% of cases of cholangiocarcinoma, are almost exclusively in intrahepatic cases and treated with targeted therapies.

Surgery is the preferred treatment option for early-stage disease, but because cholangiocarcinoma is often detected in advanced stages, many patients are not candidates for surgery. There is also an important balance in treating cholangiocarcinoma while maintaining quality of life. Although there are other options for treatment, including chemotherapy, radiation therapy, and targeted therapy, because of the symptoms and comorbidities associated with cholangiocarcinoma, patient counseling is necessary when finding an effective treatment. Physicians often have to manage the comorbidities patients with cholangiocarcinoma have before they can discuss adverse effects (AEs) that can result from treatment.

“I see most of the newly diagnosed patients on the inpatient side, so pretty symptomatic, typically metastatic disease,” Brendan Mangan, PharmD, BCOP, clinical pharmacy specialist, Penn Medicine, Philadelphia, Pennsylvania, said during the forum. “So, it’s kind of a discussion of how we can optimize their nonchemotherapy care in terms of giving them [medications] for anxiety, depression…and some pain that can be associated with it. And then picking a treatment that [the patients] will be able to tolerate. It’s a hard discussion.”

When optimizing medication selection for patients with newly diagnosed advanced cholangiocarcinoma, the panelists discussed what they take into consideration when selecting treatments. Kristin Markiewicz, PharmD, BCOP, oncology clinical pharmacy specialist, Penn Medicine, said that she finds it important to consider patients’ comorbidities and the supplements they take during treatment decisions. Anshika Singh, PharmD, BCOP, oncology clinical pharmacy specialist at Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, elaborated on that point by explaining patients who continue to take their supplements during cholangiocarcinoma treatment feel a sense of control and normality; however, compromising is necessary in some situations because supplement-related AEs can be confused with treatment-related AEs.

“I try to be as flexible as I can with their supplements, especially in a metastatic setting. If they feel like they’re [deriving] some type of benefit from them, I try not to be the person [who] stops everything,” said Singh during the forum. “But there are some known drug interactions and certain symptoms they do have to address.… Sometimes [patients have] been on [the supplements] for years and sometimes they just want—I think—to have a little bit of control of their disease.”

In addition, Mangan noted that patients and oncologists may find comfort in treatments that have a longer history of use. For example, Mangan noted that pemigatinib (Pemazyre; Incyte) is a patientpreferred option in his experience because it is not a newer agent, has improved overall survival up to 24 months, and is tolerated well; however, some patients have reservations due to the drug’s inconsistent dosing schedule (2 weeks on, 1 week off) compared with the other 2 oral targeted therapy drugs, ivosidenib (Tibsovo; Servier) and futibatinib (Lytgobi; Taiho Pharmaceutical), which are taken once daily.

The panelists also noted that following results of clinical trials is necessary to keep well informed of targeted therapy treatment options that become available for patients. They explained further that this is especially true in the second-line setting because the use of immunotherapy in the first line can affect future treatment options.

“I think it does really impact our treatment decision.… I think that it’s really hard to [choose the next treatment],” said Yenamandra in the forum. “[We are] kind of grasping at straws or even turning toward clinical trials or registry after that.”

Pharmacists can help ensure undertreatment for patients is not an issue after either lack of response to or toxicity from first-line treatment. Rose DiMarco, PharmD, BCPS, BCOP, oncology pharmacy manager, Thomas Jefferson University Hospital, emphasized that although standard first-line therapies should be used as much as possible, patient symptoms can result in intolerance to treatment. In some cases, patients will have to start on lower doses of treatment to see whether they can tolerate it and identify treatment-related AEs.

A best practice for pharmacists in this setting includes consultations with physicians, patients, and payers. Markiewicz described that her institution has a team of pharmacists who collaborate with financial assistance programs regularly and who then apply to foundations or grant manufacturer programs to determine which programs patients may qualify for. DiMarco explained that her institution’s pharmacists work closely with financial advisers and that the advisers can see what drugs are ordered for patients, helping them find grants specifically for those drugs.

Further, updates made by the National Comprehensive Cancer Network (NCCN) can lead to complications in standards of care, depending on providers and their recommendations. Sophia Gilardone, PharmD, BCOP, clinical oncology pharmacist at Penn Medicine, explained that it is necessary to appropriately place the patient on the proper regimen using biomarker testing, with different options for the patient if they are not the right candidate. Bottiglieri described that significant changes made by NCCN can also feel like “starting over” because of medication costs, whether medications are FDA approved or not, and timing concerns.

Gilardone stated that although recommendations for changes cannot always be made, collaboration with the provider is necessary to reduce future complications. “We don’t have control of [NCCN changes]…and it gets complicated if the provider doesn’t believe [it],” Gilardone said. “But for some [hematologic malignancies] and even some of the [gynecological diseases], for example, our pathways are not great for that, and I don’t know why. So, it can be complicated depending on the providers and what their recommendations are, especially when we don’t help them.”

The panelists emphasized the practical aspects of treatment exploration, patient comorbidity and symptom management, and interdisciplinary collaboration, which they explained can underscore the challenges that pharmacists face during the patient treatment process for this disease state. However, Bottiglieri noted that these challenges extend beyond patients with cholangiocarcinoma and affect every patient, making it essential for pharmacists to continue to provide quality-of-life care.