Hussein A Tawbi1, Peter A Forsyth2, F Stephen Hodi3, Christopher D Lao4, Stergios J Moschos5, Omid Hamid6, Michael B Atkins7, Karl Lewis8, Reena P Thomas9, John A Glaspy10, Sekwon Jang11, Alain P Algazi12, Nikhil I Khushalani13, Michael A Postow14, Anna C Pavlick15, Marc S Ernstoff16, David A Reardon17, Igor Puzanov18, Ragini R Kudchadkar19, Ahmad A Tarhini13, Anne Sumbul20, Jasmine I Rizzo21, Kim A Margolin22. 1. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX. 2. Department of Neuro-Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL. 3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA. 4. Department of Dermatology, University of Michigan, Ann Arbor, MI. 5. Division of Hematology & Oncology, The University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC. 6. Department of Translational Research & Immunotherapy, The Angeles Clinic and Research Institute, A Cedars-Sinai Affilliate, Los Angeles, CA. 7. Department of Medical Oncology,Georgetown-Lombardi Comprehensive Cancer Center, Washington DC. 8. Department of Medical Oncology, University of Colorado Comprehensive Cancer Center, Aurora, CO. 9. Department of Neurology, Stanford University Cancer Center, Stanford, CA. 10. Department of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA. 11. Department of Medicine, Inova Schar Cancer Institute, Virginia Commonwealth University, Fairfax, VA. 12. Department of Hematology & Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA. 13. Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL. 14. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY. 15. Department of Medical Oncology, Weill Cornell Medicine, New York, NY. 16. Department of Immuno-Oncology, Division of Cancer Treatment and Diagnosis, National Cancer Institute at the National Institutes of Health, Rockville, MD. 17. Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA. 18. Department of Medical Oncology, Roswell Park Cancer Institute, Buffalo, NY. 19. Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA. 20. Biostatistics, Bristol Myers Squibb Company, Princeton, NJ. 21. Oncology Clinical Development, Bristol Myers Squibb Company, Princeton, NJ. 22. Department of Medical Oncology, City of Hope, Duarte, CA.
Abstract
BACKGROUND: In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients. METHODS: Patients with measurable MBM, 0.5-3.0 cm, were enrolled into Cohort A (asymptomatic) or Cohort B (stable neurologic symptoms and/or receiving corticosteroids). Nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg, were given intravenously every 3 weeks x4, followed by nivolumab, 3 mg/kg, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint was intracranial clinical benefit rate (CBR; complete response [CR], partial response [PR], or stable disease ≥6 months). RESULTS: Symptomatic patients (N = 18) received a median of one nivolumab and ipilimumab combination dose, and had an intracranial CBR of 22.2%. Two of 12 patients on corticosteroids had CR; 2 responded among the 6 not on corticosteroids. Median intracranial progression-free survival (PFS) and overall survival (OS) were 1.2 and 8.7 months, respectively. In contrast, with 20.6 months of follow-up, we confirmed an intracranial CBR of 58.4% in asymptomatic patients (N = 101); median duration of response, PFS, and OS were not reached. No new safety signals were observed. CONCLUSIONS: Nivolumab plus ipilimumab provides durable clinical benefit for asymptomatic patients with MBM and should be considered for first-line therapy. This regimen has limited activity in MBM patients with neurologic symptoms and/or requiring corticosteroids, supporting the need for alternative approaches and methods to reduce the dependency on corticosteroids.
BACKGROUND: In patients with melanoma and asymptomatic brain metastases (MBM), nivolumab plus ipilimumab provided an intracranial response rate of 55%. Here, we present first report for patients who were symptomatic and/or required corticosteroids and updated data for asymptomatic patients. METHODS:Patients with measurable MBM, 0.5-3.0 cm, were enrolled into Cohort A (asymptomatic) or Cohort B (stable neurologic symptoms and/or receiving corticosteroids). Nivolumab, 1 mg/kg, and ipilimumab, 3 mg/kg, were given intravenously every 3 weeks x4, followed by nivolumab, 3 mg/kg, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint was intracranial clinical benefit rate (CBR; complete response [CR], partial response [PR], or stable disease ≥6 months). RESULTS: Symptomatic patients (N = 18) received a median of one nivolumab and ipilimumab combination dose, and had an intracranial CBR of 22.2%. Two of 12 patients on corticosteroids had CR; 2 responded among the 6 not on corticosteroids. Median intracranial progression-free survival (PFS) and overall survival (OS) were 1.2 and 8.7 months, respectively. In contrast, with 20.6 months of follow-up, we confirmed an intracranial CBR of 58.4% in asymptomatic patients (N = 101); median duration of response, PFS, and OS were not reached. No new safety signals were observed. CONCLUSIONS:Nivolumab plus ipilimumab provides durable clinical benefit for asymptomatic patients with MBM and should be considered for first-line therapy. This regimen has limited activity in MBM patients with neurologic symptoms and/or requiring corticosteroids, supporting the need for alternative approaches and methods to reduce the dependency on corticosteroids.
Authors: Ayal A Aizer; Nayan Lamba; Manmeet S Ahluwalia; Kenneth Aldape; Adrienne Boire; Priscilla K Brastianos; Paul D Brown; D Ross Camidge; Veronica L Chiang; Michael A Davies; Leland S Hu; Raymond Y Huang; Timothy Kaufmann; Priya Kumthekar; Keng Lam; Eudocia Q Lee; Nancy U Lin; Minesh Mehta; Michael Parsons; David A Reardon; Jason Sheehan; Riccardo Soffietti; Hussein Tawbi; Michael Weller; Patrick Y Wen Journal: Neuro Oncol Date: 2022-10-03 Impact factor: 13.029
Authors: Hussein A Tawbi; Peter A Forsyth; F Stephen Hodi; Alain P Algazi; Omid Hamid; Christopher D Lao; Stergios J Moschos; Michael B Atkins; Karl Lewis; Michael A Postow; Reena P Thomas; John Glaspy; Sekwon Jang; Nikhil I Khushalani; Anna C Pavlick; Marc S Ernstoff; David A Reardon; Ragini Kudchadkar; Ahmad Tarhini; Caroline Chung; Corey Ritchings; Piyush Durani; Margarita Askelson; Igor Puzanov; Kim A Margolin Journal: Lancet Oncol Date: 2021-11-10 Impact factor: 54.433
Authors: Annemarie C Eggen; Thijs T Wind; Ingeborg Bosma; Miranda C A Kramer; Peter Jan van Laar; Hiska L van der Weide; Geke A P Hospers; Mathilde Jalving Journal: Cancer Med Date: 2021-11-05 Impact factor: 4.452
Authors: Peter Kar Han Lau; Breon Feran; Lorey Smith; Arian Lasocki; Ramyar Molania; Kortnye Smith; Alison Weppler; Christopher Angel; Damien Kee; Prachi Bhave; Belinda Lee; Richard J Young; Amir Iravani; Hanxian Aw Yeang; Ismael A Vergara; David Kok; Kate Drummond; Paul Joseph Neeson; Karen E Sheppard; Tony Papenfuss; Benjamin J Solomon; Shahneen Sandhu; Grant A McArthur Journal: J Immunother Cancer Date: 2021-10 Impact factor: 12.469
Authors: Annemarie C Eggen; Geke A P Hospers; Ingeborg Bosma; Miranda C A Kramer; Anna K L Reyners; Mathilde Jalving Journal: BMC Cancer Date: 2022-03-05 Impact factor: 4.430
Authors: María Martínez-García; Sonia Servitja Tormo; Noelia Vilariño Quintela; Ana Arance Fernández; Alfonso Berrocal Jaime; Blanca Cantos Sánchez de Ibargüen; Sonia Del Barco Berrón; Rosario García Campelo; Regina Gironés Sarrió; Juan Manuel Sepúlveda-Sánchez Journal: Clin Transl Oncol Date: 2022-03-08 Impact factor: 3.405