Managing progressive disease in patients with GIST: factors to consider besides acquired secondary tyrosine kinase inhibitor resistance.
The use of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumors (GIST). Currently, imatinib mesylate is the standard first-line treatment for unresectable and/or metastatic GIST, extending recurrence-free and overall survival for many patients. Nonetheless, eventual progression during imatinib therapy is prevalent, and the development of treatment paradigms for managing GIST progression is of importance. Sunitinib malate has been approved as a second-line treatment for unresectable and/or metastatic GIST and is an option for patients who are intolerant to imatinib or experience disease progression due to acquired resistance, otherwise referred to as secondary resistance. In many cases, however, there may be other causes for GIST progression besides secondary resistance, and consideration of these factors is necessary before switching to second-line treatment. This review presents a treatment strategy for GIST patients who have progressed after initial imatinib responsiveness and addresses necessary considerations that include instances of false progression, insufficient TKI plasma levels, and patient non-adherence. In situations where true progression has occurred, patients may benefit from imatinib dose escalation. Surgery also provides a viable option for patients with stable disease or limited progression, and may prevent and/or delay the development of resistant clones by reducing tumor burden. Switching to second-line therapy with sunitinib should be considered for imatinib-intolerant or -resistant GIST patients.
Department of Sarcoma Medical Oncology, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. spatel@mdanderson.org
Shreyaskumar
S
Patel
D001549:Benzamides; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use; D010349:Patient Compliance; D010879:Piperazines / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib