Abstract
Purpose
Prior data suggest driver-mutated NSCLC, especially EGFR and ALK tumors, poorly respond to immunotherapy. However, little research using real-world cohorts have been performed, nor is it clear whether PD-L1 and smoking history are predictive of outcomes in such tumors. This study assessed rwPFS in a large cohort with driver-mutated advanced NSCLC treated with single-agent PD-1/PDL-1 inhibitors.
Methods
Real-world data from 1746 patients were analyzed and rwPFS with immunotherapy was determined for EGFR, ALK, BRAF, and KRAS tumors. Kaplan–Meier curves characterized rwPFS and correlated with PD-L1 and smoking history. Comparisons were tested using log-rank.
Results
Median rwPFS and the percent progression-free at 12 months were greater among KRAS (3.3 months, 21.1%) and BRAF (3.6 months, 20.6%) as compared to EGFR (2.5 months, 8.1%) and ALK tumors (2.3 months, 11.2%). KRAS tumors with PD-L1 ≥ 1% had longer rwPFS than PD-L1 < 1% tumors (4.1 versus 3.2 months, p = 0.001). PD-L1 positivity did not predict rwPFS in EGFR, ALK, or BRAF tumors. However, a smoking history was associated with longer rwPFS in EGFR (2.6 versus 2.3 months, p = 0.048) and ALK tumors (3.0 versus 2.1 months, p = 0.049) as compared to no smoking history.
Conclusion
Real-world PFS with immunotherapy was greater in KRAS and BRAF as compared to EGFR and ALK tumors. PD-L1 positivity was predictive in KRAS and not associated with rwPFS in other mutation types. While median rwPFS was short for EGFR and ALK tumors, small subsets were progression-free at 12 months. Better characterizing these subsets that benefit, along with developing strategies to overcome immunotherapy resistance in EGFR/ALK tumors are needed.
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Data availability
The data underlying this article were provided by Flatiron Health via a data sharing agreement.
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Acknowledgements
This work was supported by the Comprehensive Cancer Center Program at Fox Chase (P30 CA006927) and by the TUFCCC/HC Regional Comprehensive Cancer Health Disparity Partnership, Award Number U54 CA221704(5) from the National Cancer Institute of National Institutes of Health (NCI/NIH).
Funding
This work was supported by the Comprehensive Cancer Center Program at Fox Chase (P30 CA006927) and by the TUFCCC/HC Regional Comprehensive Cancer Health Disparity Partnership, Award Number U54 CA221704(5) from the National Cancer Institute of National Institutes of Health (NCI/NIH).
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JNB: conceptualization, investigation, formal analysis, writing—original draft preparation. JRB: investigation, writing—review and editing. EAH: formal analysis, writing—review and editing. EAR: writing—review and editing. MLC: writing—review and editing. JT: conceptualization, investigation, writing—review and editing.
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Supplemental Fig.
Kaplan-Meier curves of real-world progression free survival in EGFR and KRAS tumors by PD-L1 expression categories (< 1%, 1 – 49%, ≥ 50%) (PPTX 82 kb)
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Bodor, J.N., Bauman, J.R., Handorf, E.A. et al. Real-world progression-free survival (rwPFS) and the impact of PD-L1 and smoking in driver-mutated non-small cell lung cancer (NSCLC) treated with immunotherapy. J Cancer Res Clin Oncol 149, 1755–1763 (2023). https://doi.org/10.1007/s00432-022-04089-9
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DOI: https://doi.org/10.1007/s00432-022-04089-9