LBA 03 - SWOG S1827/MAVERICK: A Randomized Phase III Trial of Brain MRI Surveillance with and without Prophylactic Cranial Irradiation (PCI) for Small-Cell Lung Cancer (SCLC)
Presenter(s)
C. G. Rusthoven1,2, M. Redman3,4, P. D. Brown5, J. S. Wefel6, J. Miao3, M. H. Hsieh3,4, J. Honce7, J. Unger4, N. L. Henry8, A. A. Patel9, D. Y. Gelblum10, J. Greenland11, D. Moghanaki12, T. Biswas13, L. R. Alder14, N. S. McCall15, J. Gray16, and K. Kelly17; 1Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO, 2University of North Carolina at Chapel Hill, Chapel Hill, NC, 3SWOG Statistics and Data Management Center, Seattle, WA, 4Fred Hutchinson Cancer Center, Seattle, WA, 5Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 6Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 7University of Colorado, Aurora, CO, 8University of Michigan, Ann Arbor, MI, 9Yale University School of Medicine, New Haven, CT, 10Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 11Eastern Health Cancer Care Program, St. John''s, NL, Canada, 12Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA, 13Department of Radiation Oncology, University of Florida College of Medicine, Gainesville, FL, 14Department of Medical Oncology, Duke University Medical Center, Durham, NC, 15Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, 16Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 17Scientific Affairs, International Association for the Study of Lung Cancer, Sacramento, CA
Purpose/Objective(s):
For SCLC, studies from the pre-MRI era demonstrated a reduction in brain metastases (BM) and improved overall survival (OS) with PCI. We hypothesized that brain MRI surveillance without PCI would result in improved cognitive failure free survival (CFFS) without a decline in OS.Materials/Methods:
This international phase III trial enrolled patients (pts) with limited (LS) and extensive-stage (ES) SCLC who had completed initial therapy, with no BM on MRI prior to enrollment. Pts were randomized to MRI surveillance +/- PCI (25 Gy in 10 Fx), stratified by stage (LS/ES), receipt of immunotherapy (IO), and PS (0-1 vs 2). MRIs were q3 months during year 1 and q6 months during year 2 in both arms. Cognitive testing was performed at the same time points using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association, and Trail Making Test. The primary objective was to compare CFFS defined as the time to first cognitive failure (CF) on any test or death, using a 1-sided 0.05 level log-rank test. The key secondary objective was to evaluate if OS was not inferior with MRI alone, with a non-inferiority margin for the upper bound 90% CI of 1.25. The final OS analysis will take place after 190 deaths. Additional objectives included comparing cumulative incidence of CF by Fine-Gray, BM-free survival, and toxicities. Patient reported cognitive concerns (via the MDASI-BT cognitive factor score and the PROMIS CFSF4a) and overall quality of life (QOL) (single-item LASA) were analyzed and preliminary results are presented.Results:
From 01/2020 to 12/2025, 304 pts were randomly assigned; 68% had LS-SCLC. The median follow-up for living pts is 22 months. CFFS was improved with MRI alone (HR 0.60, 90% CI 0.46-0.78, p=0.001). Subgroup analyses of CFFS demonstrated no significant differences in the benefit of MRI alone by either stage (LS/ES, interaction-p=0.92) or receipt of IO (yes/no, interaction-p=0.25). Of pts receiving PCI, 77% had hippocampal-avoidant (HA)-PCI. CFFS was superior for pts in the MRI arm who would have received HA-PCI (declared pre-randomization) compared to HA-PCI (HR 0.63, 90% CI 0.47-0.83, p=0.006). Preliminary analysis of OS at 128 deaths suggests no difference in OS (HR for MRI alone vs MRI+PCI: 0.90, 90% CI 0.67-1.20). There was a decreased risk of CF with MRI alone (subdistribution HR 0.62, 90% CI 0.48-0.79, p=0.001). At the Day 180 primary endpoint assessment for patient reported outcomes, no statistically significant differences in PROMIS or MDASI cognitive concerns (p=0.07 and 0.69, respectively) were found; however, pre-specified longitudinal modeling demonstrated improvements with MRI alone in PROMIS cognitive concerns that were significant at all time points and improved overall QOL on LASA at 90 and 180 days (all p<0.05).Conclusion:
Compared to MRI+PCI, MRI alone is associated with superior CFFS, reduced cognitive failure, and improvements in longitudinal QOL outcomes. These results support MRI surveillance alone as the standard of care for pts with SCLC.