Comparative Analysis of Intracranial Response Assessment Criteria in Patients With Melanoma Brain Metastases Treated With Combination Nivolumab + Ipilimumab in CheckMate 204
Abstract
PURPOSE In CheckMate 204, nivolumab + ipilimumab showed high intracranial (IC) objective response rates (icORRs) in patients with melanoma brain metastases (MBMs). Using icORR as a surrogate for overall survival (OS) has prompted use of alternate response criteria. To set the stage for harmonized MBM trials, the aim of this exploratory analysis was to determine icORR using several response criteria and examine correlations of response with survival. METHODS Patients (N = 119) with ≥one unirradiated MBMs received nivolumab + ipilimumab every 3 weeks (four doses), followed by nivolumab every 2 weeks for ≤24 months. Blinded review icORR was assessed with modified RECIST (mRECIST), Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM; 5 mm and 10 mm cutoffs), and volumetric criteria (5 mm and 10 mm). Using a 6-week response landmark, IC progression-free survival (icPFS) and OS were compared for responders versus nonresponders. RESULTS icORR was higher with mRECIST and volumetric criteria than with RANO-BM or RECIST. mRECIST and volumetric response also showed stronger correlations with icPFS and OS. mRECIST responders who were RANO-BM 5 mm nonresponders (n = 14) had similar OS to RANO-BM 5 mm responders (n = 41). Clinical deterioration affected RANO-BM icORR; however, when assessed only radiographically without deterioration, RANO-BM 5 mm performed similarly to mRECIST. Among 41 patients with target lesions all <10 mm, responder icPFS and OS were similar to those of responders in the total population, indicating that response could be accurately determined in these patients. CONCLUSION This analysis supports mRECIST or radiographic-only RANO-BM 5 mm as reliable assessment scales in MBM trials. Volumetric response correlated with survival, supporting its application in future trials. Response could be accurately determined in patients with MBMs all <10 mm, supporting the inclusion of patients with MBMs ≥5 mm in future trials.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Raymond Y. Huang
Gilbert Youssef
Dana-Farber Cancer Institute, Boston, MA
Thomas Nelson
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA
Patrick Y. Wen
Peter Forsyth
Departments of Neuro-Oncology and Cell Biology, Moffitt Cancer Center, Tampa, FL
F. Stephen Hodi
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Kim Margolin
Department of Medical Oncology, Saint John's Cancer Institute, Santa Monica, CA
Alain P. Algazi
Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
Omid Hamid
5The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Translational Research & ImmunoOncolgy, Los Angeles, United States
Christopher D. Lao
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Marc S. Ernstoff
NCI Division of Cancer Treatment and Diagnosis, Developmental Therapy Program, Bethesda, MD
Stergios J. Moschos
The University of North Carolina at Chapel Hill, Chapel Hill, NC
Michael B. Atkins
Department of Oncology Georgetown Lombardi Comprehensive Cancer Center Georgetown University Washington District of Columbia USA
Michael A. Postow
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
David A. Reardon
Diederik J. Grootendorst
Bristol Myers Squibb, Princeton, NJ
David Leung
Daiichi Sankyo, Basking Ridge, NJ
Margarita Askelson
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Corey Ritchings
From the Sandra and Edward Meyer Cancer Center (J.D.W.) and the Department of Medicine (J.D.W., M.A.P.), Weill Cornell Medicine, and Memorial Sloan Kettering Cancer Center (M.A.P.) — both in New York; Istituto Oncologico Veneto, IRCCS, Padua (V.C.-S.), European Institute of Oncology, IRCCS, Milan (P.Q.), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, IRCCS, Meldola (M.G.), University of Siena and the Center for Immuno-Oncology, University Hospital of Siena, Siena (M.M.), and Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples (P.A.A.) — all in Italy; Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland (P.R.); Texas Oncology–Baylor Charles A. Sammons Cancer Center, Dallas (C.L.C.); University Hospital Essen, the German Cancer Consortium, the National Center for Tumor Diseases–West, the Research Alliance Ruhr, Research Center One Health, and University Duisburg-Essen — all in Essen, Germany (D.S.); the College of Medicine, Swansea University, Swansea (J.W.), Brist...
Hussein A. Tawbi
The University of Texas MD Anderson Cancer Center, Houston, TX