Clinical and Genomic Characterization of Long-Term Responders Receiving Immune Checkpoint Blockade for Metastatic Non–Small-Cell Lung Cancer

Paola Ghanem, Joseph C. Murray, Melinda Hsu, Matthew Z. Guo, David S. Ettinger, Josephine Feliciano, Patrick Forde, Christine L. Hann, Vincent K. Lam, Benjamin Levy, Valsamo Anagnostou, Julie R. Brahmer, Kristen A. Marrone

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Understand from a real-world cohort the unique clinical and genomic determinants of a durable response to immune checkpoint inhibitors (ICIs). Materials and Methods: This is a retrospective study of patients with NSCLC who received any ICI-based regimen as first or second line therapy. Long-term responders (LTR) achieved an overall survival (OS) ≥ 3 years from time of treatment start, while nonresponders (NR) were patients who had an OS of 6 to 12 months from time of treatment start. Clinical and demographic covariables were collected from electronic medical records. Fisher's exact test and Mann-Whitney test were used to analyze the association of a long-term response to ICI in relation to clinical and genomic variables. All P-values were considered significant at P-value < .05. Results: A total of 72 patients were included in this study (LTR n = 37, NR n = 35). There were no significant differences in age, sex, race, and BMI between groups. The presence of liver metastases at the time of ICI initiation and PD-L1 status were not associated with LTR to ICIs. Patients in the LTR were more likely to experience irAEs at 3-,6- and 12-months. KRAS mutant tumors were numerically more common in the LTR group (n = 13 vs. 8). Conclusion: We observe no strong clinical and biomarkers of a prolonged response to ICIs. Additional large prospective cohort studies are needed to investigate the genomic footprint of long-term responders.

Original languageEnglish
Pages (from-to)109-118
Number of pages10
JournalClinical Lung Cancer
Volume25
Issue number2
DOIs
StatePublished - Mar 2024
Externally publishedYes

Keywords

  • Cancer genomics
  • Immunotherapy
  • Long-term response

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