Abstract P2-13-04: Inclusion of Patients with Leptomeningeal Disease in Phase III Randomized Clinical Trials of Patients with Advanced Breast Cancer, Lung Cancer, and Melanoma: A Systematic Review
Authors: Sharma Alisha , Corbett Kathryn , Qazi Maleeha , Soliman Hany , Sahgal Arjun , Das Sunit , Lim-Fat Mary Jane , Pond Gregory R. , Jerzak Katarzyna 
Published: March 2023

Abstract
Introduction: Leptomeningeal disease (LMD) is a late complication of metastatic cancer that significantly limits patient survival. LMD is most prevalent in patients with melanoma, lung, and breast cancer, with incidence reaching 24.1% among those treated for brain metastases with both surgery and radiotherapy. As systemic treatment advances in oncology continue to improve patient survival, the incidence of LMD is expected to rise. This necessitates increased efforts to identify effective LMD therapies. Further, recent reporting of focal LMD in asymptomatic patients indicates that unique categories of LMD exist which may not necessarily portend a dismal prognosis. Unfortunately, exclusion of these patients from clinical trials has resulted in a paucity of high-quality evidence to guide management in this patient population. We therefore conducted a systematic review to determine the proportion and characteristics of phase III randomized clinical trials in breast cancer, lung cancer, and melanoma that included patients with LMD and/or included LMD-specific outcomes.
Methods: The online ClinicalTrials.gov database was searched on December 22, 2020 for eligible phase III randomized control trials. No time limits were applied. The 1619 search results were screened by two independent reviewers for randomized, multi-arm therapeutic trials in advanced breast cancer, lung cancer, or melanoma.
Results: 245 trials were included in this review, 75/245 (30.6%) of which included LMD-specific enrollment criteria. 67/245 (27.3%) trials explicitly excluded all patients with LMD, while 8 trials (3.3%) allowed conditional enrollment of patients with LMD; these stipulated that LMD must be asymptomatic/stable, and in some cases, treated. All 8 trials which conditionally allowed LMD patients to enroll were lung cancer trials. No temporal trend towards LMD inclusion was noted. CNS-specific outcomes, which did not include specific mention of LMD, were noted in 13/245 (5.4%) trials, 2 (15.4%) of which used standardized response criteria. No trials included LMD-specific outcomes.
Conclusion: In this review, high rates of LMD exclusion and a complete lack of LMD-specific outcomes were noted in phase III trials for advanced breast cancer, lung cancer, and melanoma, despite these cancers carrying the highest risks of LMD. Lung cancer trials were most likely to include patients with LMD; this may be due to differences in tumor biology, drug penetration in the CNS and drug efficacy. Standardized and validated measures should be integrated into clinical trial design to facilitate inclusion of these patients when feasible and allow for meaningful assessment of LMD response to therapy.
Table 1: Trial factors associated with exclusion of patients with leptomeningeal metastases a.based on study start date listed on clinicaltrials.gov, defined as “the actual date on which the first participant was enrolled in a clinical study.” b.based on studies with known location. Statistical test was between intercontinental versus single continent studies.
Citation Format: Alisha Sharma, Kathryn Corbett, Maleeha Qazi, Hany Soliman, Arjun Sahgal, Sunit Das, Mary Jane Lim-Fat, Gregory R. Pond, Katarzyna Jerzak. Inclusion of Patients with Leptomeningeal Disease in Phase III Randomized Clinical Trials of Patients with Advanced Breast Cancer, Lung Cancer, and Melanoma: A Systematic Review [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-04.