expert roundtables

Whole-Patient Care for Patients With Progressive Gastrointestinal Stromal Tumors

by Suzanne George, MD; Richard F. Riedel, MD; and Jonathan C. Trent, MD, PhD

Overview

The management of side effects from tyrosine kinase inhibitor (TKI) therapy often requires a multidisciplinary approach, with aggressive supportive care and patient education. Gaining control of the gastrointestinal stromal tumors (GIST) and optimizing treatment tolerability both influence quality of life (QOL).

Q:

How are patients with advanced, progressive GIST best supported? What are some key aspects of whole-patient care?

Richard F. Riedel, MD

Associate Professor of Medicine With Tenure
Division of Medical Oncology
Duke University Medical Center
Associate Director of Clinical Research
Duke Sarcoma Center
Duke Cancer Institute
Durham, NC

“ . . . it is important to partner with patients in providing education and supportive care, as all therapies have the potential for toxicity.”

Richard F. Riedel, MD

I regularly tell my patients that their QOL is what is most important to me. If a therapy is significantly affecting their QOL, I would argue that the therapy is not worth continuing without some sort of adjustment. When considering systemic therapy in GIST, it is important to partner with patients in providing education and supportive care, as all therapies have the potential for toxicity. 

We routinely use a multidisciplinary team that includes pharmacists, dieticians, and other subspecialists to support our management plan. Pharmacists can help educate patients on the potential side effects of drugs, particularly individuals who are newly initiating therapy. They routinely make follow-up telephone calls to help assess and mitigate side effects that are associated with treatment. Dieticians can help patients with the decreased appetite, anorexia, and nausea that may be associated with some agents, while encouraging them to maintain adequate nutrition. Since some medications have the potential to affect blood pressure and thyroid function, medical subspecialists may be asked to assist in ongoing assessments and management. We also work with our palliative care specialists, given the myriad of potential disease- and treatment-related side effects that can occur. It truly requires a team effort.

In addition to aggressive supportive care, other strategies to help patients tolerate therapy include brief drug holidays, intermittent dose reductions, and alternative dosing schedules. In our experience, these approaches generally allow individuals to maintain dose intensity. Overall, our goal is to provide patients with the tools that they need to be able to advocate for themselves and to feel comfortable communicating with us, their care providers. 

Jonathan C. Trent, MD, PhD

Professor of Medicine
Associate Director for Clinical Research
Sylvester Comprehensive Cancer Center
University of Miami Miller School of Medicine
Miami, FL

“Our approach, in general, is to try to preserve the dose intensity because there are data showing that there is a dose-response relationship with TKI therapy. To maintain dose intensity, we are very aggressive in managing the side effects.”

Jonathan C. Trent, MD, PhD

Our approach, in general, is to try to preserve the dose intensity because there are data showing that there is a dose-response relationship with TKI therapy. To maintain dose intensity, we are very aggressive in managing the side effects. It is helpful to know whether a pattern related to the adverse event(s) of a particular therapy can be identified so that you can intervene and try to prevent it from occurring. For instance, if a patient reports having diarrhea 2 hours after taking imatinib, we tell them to start taking the imatinib with an antidiarrheal medication (eg, loperamide) to prevent the side effect from occurring altogether rather than treating the diarrhea once it occurs. We do the same thing for nausea. 

These side effects are easier to treat when they are addressed early. Our nurse practitioners have a lot of experience with these agents, and they sit down with patients for 1-hour therapy treatment education sessions before we start the treatments. The nurse practitioners review the potential adverse events with patients and provide them with educational PDFs that list the side effects of each medication and explain how to manage them. Most importantly, the PDFs include instructions for patients to call us if they experience any serious side effects. 

Suzanne George, MD

Clinical Research Director, Sarcoma Center
Dana-Farber Cancer Institute
Associate Professor of Medicine
Harvard Medical School
Boston, MA

" . . . resources can be personalized for each individual patient’s experience. . . . It is important to optimize that support so that we can ensure that the medication is providing more benefit than toxicity.”

Suzanne George, MD

There is a lot that we can do to help patients tolerate medications for GIST, including supportive care and the incorporation of other specialties to help the patients cope with the treatment regimen. When starting a new medication, it is very important to stay in close touch with your team because there are many tools available to help people tolerate the medications. These resources can be personalized for each individual patient’s experience. Sometimes we need to take drug holds or breaks, sometimes we need to reduce the dose, and sometimes we need to get creative about the dosing schedule. It is important to optimize that support so that we can ensure that the medication is providing more benefit than toxicity. 

There are differences in tolerability profiles between each of the TKIs, and we discuss these differences with patients; however, it is important to emphasize that we can generally help them through these side effects. At our center, we have been able to help people tolerate most of the drugs that are in the armamentarium for GIST, so we are typically able to keep patients on the US Food and Drug Administration–approved sequence of TKI inhibitors with imatinib in the first line, sunitinib in the second line, regorafenib in the third line, and ripretinib in the fourth line. 

The INTRIGUE trial compared second-line therapy with ripretinib vs with sunitinib and reported that, overall, sunitinib and ripretinib have comparable progression-free survivals, although the trial was designed to show superiority with ripretinib, which was not shown. Data from INTRIGUE were analyzed for patient-related QOL outcomes, and findings indicated that QOL metrics were better for ripretinib than for sunitinib, given at its approved oral dosing schedule for GIST. While we may use dose-reduction strategies for sunitinib to improve tolerability, the full-indicated dose is used globally. There are also data in the fourth-line setting suggesting that ripretinib is well tolerated. 

References

Bauer S, George S, von Mehren M, Heinrich MC. Early and next-generation KIT/PDGFRA kinase inhibitors and the future of treatment for advanced gastrointestinal stromal tumor. Front Oncol. 2021;11:672500. doi:10.3389/fonc.2021.672500

Blay J-Y, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial [published correction appears in Lancet Oncol. 2020;21(7):e341]. Lancet Oncol. 2020;21(7):923-934. doi:10.1016/S1470-2045(20)30168-6

Den Hollander D, Van der Graaf WTA, Desar IME, Le Cesne A. Predictive factors for toxicity and survival of second-line sunitinib in advanced gastrointestinal stromal tumours (GIST). Acta Oncol. 2019;58(11):1648-1654. doi:10.1080/0284186X.2019.1637017

Dudzisz-Śledź M, Bylina E, Teterycz P, Rutkowski P. Treatment of metastatic gastrointestinal stromal tumors (GIST): a focus on older patients. Drugs Aging. 2021;38(5):375-396. doi:10.1007/s40266-021-00841-x

Gelderblom H, Jones RL, Blay J-Y, et al. Patient reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after imatinib treatment in INTRIGUE: a phase 3 open-label study [abstract 11541]. Abstract presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022.

Heinrich MC, Jones RL, Gelderblom H, et al. INTRIGUE: a phase III, randomized, open-label study to evaluate the efficacy and safety of ripretinib versus sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib [abstract 359881]. Abstract presented at: January 2022 American Society of Clinical Oncology Plenary Series; January 25, 2022.

Kelly CM, Gutierrez Sainz L, Chi P. The management of metastatic GIST: current standard and investigational therapeutics. J Hematol Oncol. 2021;14(1):2. doi:10.1186/s13045-020-01026-6

Klug LR, Khosroyani HM, Kent JD, Heinrich MC. New treatment strategies for advanced-stage gastrointestinal stromal tumours. Nat Rev Clin Oncol. 2022;19(5):328-341. doi:10.1038/s41571-022-00606-4

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