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Durable disease control with local treatment for oligoprogression of metastatic solid tumors treated with immune
Kunal K Sindhu1, Amanda Leiter2, Erin Moshier3
1Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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.
Insights
Oligoprogression, defined as limited tumor growth during immune checkpoint inhibitor therapy, occurs in a small subset of patients. Local therapy for these sites can lead to durable disease control and prolonged progression-free survival.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Progression
Background:
- Oligometastatic disease is recognized, but oligoprogression remains less characterized.
- Oligoprogression is particularly relevant for immune checkpoint inhibitors (CPI) due to their mechanism and acquired resistance.
- This study investigates oligoprogression incidence and local therapy impact in patients on CPI.
Purpose of the Study:
- To characterize the incidence of oligoprogression in patients receiving CPI.
- To explore the impact of local therapy on outcomes in patients with oligoprogression.
- To define oligoprogression in the context of advanced solid tumors treated with CPI.
Main Methods:
- Retrospective analysis of advanced solid tumor patients (excluding glioblastoma) treated with PD-1, PD-L1, or CTLA-4 inhibitors.
- Oligoprogression defined as progression at ≤3 metastatic lesions outside the brain after ≥3 months of stable disease on CPI.
- Progression-free survival (PFS) calculated using Kaplan-Meier method.
Main Results:
- Oligoprogression observed in 4.1% of the entire cohort and 15.7% of patients achieving stable disease.
- 15 of 16 patients with oligoprogression received local therapy to the affected sites.
- Median PFS for oligoprogression patients receiving local therapy was 15.4 months at 25.8 months median follow-up.
Conclusions:
- Oligoprogression occurs in a subset of patients responding to CPI.
- Local therapy to oligoprogressive sites can lead to durable disease control.
- Further research is warranted to understand and manage oligoprogression.
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