Kunal K Sindhu1, Amanda Leiter2, Erin Moshier3, Jung-Yi Lin3, Emily Carroll4, Danielle Brooks2, Jennifer Ben Shimol5, Elliot Eisenberg4, Emily J Gallagher6, Richard G Stock1, Matthew D Galsky7, Michael Buckstein1. 1. Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Division of Endocrinology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 3. Institute for Healthcare Delivery Science, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 6. Division of Endocrinology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 7. Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: matthew.galsky@mssm.edu.
Abstract
BACKGROUND: While the concept of oligometastatic disease is increasingly recognized as a distinct clinical disease state, the concept of oligoprogression is less well-characterized. Oligoprogression may be particularly relevant in the context of immune checkpoint inhibitors (CPI) given the underlying mechanism of action and insights regarding acquired resistance. In this study, we sought to characterize the incidence of oligoprogression in patients on CPI and explore the impact of local therapy. MATERIALS AND METHODS: We performed a retrospective analysis of all patients with advanced solid tumors (excluding glioblastoma multiforme) who received a PD-1, PD-L1, or CTLA-4 inhibitor at a single institution between 2011 and 2017. Oligoprogression was defined as progression at ≤3 metastatic lesions outside of the brain after achieving at least stable disease on CPI for 3 months. Progression-free survival (PFS) was calculated using the Kaplan-Meier method. RESULTS: Among 425 patients treated with CPI, 390 had advanced primary solid tumors outside of the central nervous system. 321 of these patients were evaluable for response, among whom 102 achieved at least stable disease. Oligoprogression was observed in 4.1% of the entire cohort and 15.7% of patients achieving at least stable disease on CPI. Among 16 patients experiencing oligoprogression, 15 received local therapy to the oligoprogressive lesions, many of whom continued CPI. At a median follow-up of 25.8 months, the median PFS for patients with oligoprogression after local therapy was 15.4 months. CONCLUSIONS: Oligoprogression occurs in a subset of patients after an initial response to CPI. However, patients receiving local therapy to oligoprogressive sites may experience durable disease control. Further study is warranted. MICROABSTRACT: Oligoprogression was observed in 4.1% of the entire cohort of patients on immune checkpoint inhibitors in this study and 15.7% of patients achieving at least stable disease. Among 16 patients experiencing oligoprogression, 15 received local therapy. At a median follow-up of 25.8 months, the median progression-free survival for patients with oligoprogression after local therapy was 15.4 months and zero patients had died. Oligoprogression occurs in a subset of patients after an initial response to CPI and local therapy to oligoprogressive sites may result in durable disease control.
BACKGROUND: While the concept of oligometastatic disease is increasingly recognized as a distinct clinical disease state, the concept of oligoprogression is less well-characterized. Oligoprogression may be particularly relevant in the context of immune checkpoint inhibitors (CPI) given the underlying mechanism of action and insights regarding acquired resistance. In this study, we sought to characterize the incidence of oligoprogression in patients on CPI and explore the impact of local therapy. MATERIALS AND METHODS: We performed a retrospective analysis of all patients with advanced solid tumors (excluding glioblastoma multiforme) who received a PD-1, PD-L1, or CTLA-4 inhibitor at a single institution between 2011 and 2017. Oligoprogression was defined as progression at ≤3 metastatic lesions outside of the brain after achieving at least stable disease on CPI for 3 months. Progression-free survival (PFS) was calculated using the Kaplan-Meier method. RESULTS: Among 425 patients treated with CPI, 390 had advanced primary solid tumors outside of the central nervous system. 321 of these patients were evaluable for response, among whom 102 achieved at least stable disease. Oligoprogression was observed in 4.1% of the entire cohort and 15.7% of patients achieving at least stable disease on CPI. Among 16 patients experiencing oligoprogression, 15 received local therapy to the oligoprogressive lesions, many of whom continued CPI. At a median follow-up of 25.8 months, the median PFS for patients with oligoprogression after local therapy was 15.4 months. CONCLUSIONS: Oligoprogression occurs in a subset of patients after an initial response to CPI. However, patients receiving local therapy to oligoprogressive sites may experience durable disease control. Further study is warranted. MICROABSTRACT: Oligoprogression was observed in 4.1% of the entire cohort of patients on immune checkpoint inhibitors in this study and 15.7% of patients achieving at least stable disease. Among 16 patients experiencing oligoprogression, 15 received local therapy. At a median follow-up of 25.8 months, the median progression-free survival for patients with oligoprogression after local therapy was 15.4 months and zero patients had died. Oligoprogression occurs in a subset of patients after an initial response to CPI and local therapy to oligoprogressive sites may result in durable disease control.