HSR19-097: Understanding U.S. Mutational Testing Patterns and Treatment Implications in Gastrointestinal Stromal Tumors (GIST) Patients

Background: In the United States, 3,000–4,000 cases of GIST occur each year. Approximately 80% of newly diagnosed GIST harbor mutations in KIT and up to 10% harbor mutations in PDGFRA, including an activation loop mutation at amino acid 842 that is associated with treatment resistance. Most patients (pts) with metastatic GIST (mGIST) respond initially to imatinib but progress and require alternative lines of therapy. However, pts with a PDGFRα D842V mutation have absolute resistance to imatinib and little to no benefit from other therapies. NCCN and ESMO GIST guidelines recommend routine mutational testing in all pts initiating therapy, though recent publications report low testing rates in this setting. This retrospective chart audit of GIST treaters further examines mutational testing and treatment decisions to better understand current practices and educational needs. Methods: Hematologist/oncologists who practiced in academic or community settings were eligible if they treated ≥5 pts with mGIST in the past 12 months. Respondents were asked to retrieve the last 4 charts of pts with metastatic/unresectable GIST of which ≥1 received ≥3 lines of therapy and answer questions geared toward assessing patient journey from diagnosis and mutation testing through treatment choices and outcomes. Results: 105 U.S. physicians (academic: 32; community: 73) reviewed and answered questions based on 403 patient charts. Overall KIT/PDGFRA mutation testing rates prior to initiating therapy was 59%, with lower rates in community settings. Further, only 34% of surveyed community physicians indicated they always perform mutational testing before initiating therapy despite it being strongly recommended in NCCN Guidelines. Top reasons cited for not performing mutation testing included questionable therapeutic impact, not part of practice’s standard protocol, cost, and lack of tissue. In our data set, 15 pts with a PDGFRα D842V mutation were identified, 12 of whom received imatinib despite known inactivity in this population. In the overall population, pts were primarily sequenced through imatinib, sunitinib, and regorafenib, with community clinicians being less likely to use regorafenib in the third-line setting. Conclusion: Continued education is needed about the role of mutational testing in GIST to ensure optimal treatment, especially among U.S. community oncology practitioners. The data also highlight the need for novel therapies that are effective in PDGFRα D842V-driven GIST.

Abstract

Background: In the United States, 3,000–4,000 cases of GIST occur each year. Approximately 80% of newly diagnosed GIST harbor mutations in KIT and up to 10% harbor mutations in PDGFRA, including an activation loop mutation at amino acid 842 that is associated with treatment resistance. Most patients (pts) with metastatic GIST (mGIST) respond initially to imatinib but progress and require alternative lines of therapy. However, pts with a PDGFRα D842V mutation have absolute resistance to imatinib and little to no benefit from other therapies. NCCN and ESMO GIST guidelines recommend routine mutational testing in all pts initiating therapy, though recent publications report low testing rates in this setting. This retrospective chart audit of GIST treaters further examines mutational testing and treatment decisions to better understand current practices and educational needs. Methods: Hematologist/oncologists who practiced in academic or community settings were eligible if they treated ≥5 pts with mGIST in the past 12 months. Respondents were asked to retrieve the last 4 charts of pts with metastatic/unresectable GIST of which ≥1 received ≥3 lines of therapy and answer questions geared toward assessing patient journey from diagnosis and mutation testing through treatment choices and outcomes. Results: 105 U.S. physicians (academic: 32; community: 73) reviewed and answered questions based on 403 patient charts. Overall KIT/PDGFRA mutation testing rates prior to initiating therapy was 59%, with lower rates in community settings. Further, only 34% of surveyed community physicians indicated they always perform mutational testing before initiating therapy despite it being strongly recommended in NCCN Guidelines. Top reasons cited for not performing mutation testing included questionable therapeutic impact, not part of practice’s standard protocol, cost, and lack of tissue. In our data set, 15 pts with a PDGFRα D842V mutation were identified, 12 of whom received imatinib despite known inactivity in this population. In the overall population, pts were primarily sequenced through imatinib, sunitinib, and regorafenib, with community clinicians being less likely to use regorafenib in the third-line setting. Conclusion: Continued education is needed about the role of mutational testing in GIST to ensure optimal treatment, especially among U.S. community oncology practitioners. The data also highlight the need for novel therapies that are effective in PDGFRα D842V-driven GIST.

Background: In the United States, 3,000–4,000 cases of GIST occur each year. Approximately 80% of newly diagnosed GIST harbor mutations in KIT and up to 10% harbor mutations in PDGFRA, including an activation loop mutation at amino acid 842 that is associated with treatment resistance. Most patients (pts) with metastatic GIST (mGIST) respond initially to imatinib but progress and require alternative lines of therapy. However, pts with a PDGFRα D842V mutation have absolute resistance to imatinib and little to no benefit from other therapies. NCCN and ESMO GIST guidelines recommend routine mutational testing in all pts initiating therapy, though recent publications report low testing rates in this setting. This retrospective chart audit of GIST treaters further examines mutational testing and treatment decisions to better understand current practices and educational needs. Methods: Hematologist/oncologists who practiced in academic or community settings were eligible if they treated ≥5 pts with mGIST in the past 12 months. Respondents were asked to retrieve the last 4 charts of pts with metastatic/unresectable GIST of which ≥1 received ≥3 lines of therapy and answer questions geared toward assessing patient journey from diagnosis and mutation testing through treatment choices and outcomes. Results: 105 U.S. physicians (academic: 32; community: 73) reviewed and answered questions based on 403 patient charts. Overall KIT/PDGFRA mutation testing rates prior to initiating therapy was 59%, with lower rates in community settings. Further, only 34% of surveyed community physicians indicated they always perform mutational testing before initiating therapy despite it being strongly recommended in NCCN Guidelines. Top reasons cited for not performing mutation testing included questionable therapeutic impact, not part of practice’s standard protocol, cost, and lack of tissue. In our data set, 15 pts with a PDGFRα D842V mutation were identified, 12 of whom received imatinib despite known inactivity in this population. In the overall population, pts were primarily sequenced through imatinib, sunitinib, and regorafenib, with community clinicians being less likely to use regorafenib in the third-line setting. Conclusion: Continued education is needed about the role of mutational testing in GIST to ensure optimal treatment, especially among U.S. community oncology practitioners. The data also highlight the need for novel therapies that are effective in PDGFRα D842V-driven GIST.

Corresponding Author: Khalid Mamlouk, PharmD

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