Patterns of Failure in Metastatic NSCLC Treated With First Line Pembrolizumab and Use of Local Therapy in Patients With Oligoprogression

Clin Lung Cancer. 2024 Jan;25(1):50-60.e6. doi: 10.1016/j.cllc.2023.09.002. Epub 2023 Sep 17.

Abstract

Introduction: The patterns of failure (POF) for metastatic non-small-cell lung cancer (mNSCLC) treated with immunotherapy are not well established.

Methods: We conducted a retrospective cohort study of mNSCLC that received first-line pembrolizumab with or without chemotherapy at a single academic center from 2015 to 2021. We defined POF with 2 classifications: 1) local, regional, or distant failure, or 2) failure in existing lesions, new lesions, or a combination. Oligoprogression was defined as disease progression (PD) in ≤3 sites of failure. Overall survival (OS) was measured via Kaplan-Meier and modelled with Cox regression.

Results: Of 298 patients identified, 198 had PD. Using POF classification 1, most failures were distant (43.9%) or a combination of locoregional and distant (34.4%). For POF classification 2, failures occurred in a combination of new and existing lesions (45.0%), existing lesions alone (33.3%), or in new lesions only (21.7%). Oligoprogression occurred in 39.9% (n = 79) cases. Median OS was higher in the following: PD in existing lesions vs. new or new + existing lesions (28.7 vs. 20.2 vs. 13.9 months, P < .001) and oligoprogression vs. polyprogression (35.1 vs. 12.2 months, P < .001). In oligoprogression, median OS was better for those who received radiation to all sites of PD (62.2 months) than for those who changed systemic therapy (22.9 months, P = .007). On multivariable analysis, radiation for oligoprogression (HR 0.35, 95% CI: 0.20-0.62, P < .001) was associated with improved OS.

Conclusions: In mNSCLC treated with pembrolizumab, oligoprogression is relatively common. Randomized data are needed to define the benefits of radiation in oligoprogressive mNSCLC.

Keywords: LCT; NSCLC; Oligoprogression; Pembrolizumab; SBRT.

MeSH terms

  • Antibodies, Monoclonal, Humanized
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Lung Neoplasms* / pathology
  • Retrospective Studies

Substances

  • pembrolizumab
  • Antibodies, Monoclonal, Humanized