| Autor: |
Christopoulos, Petros, Harel, Michal, McGregor, Kimberly, Brody, Yehuda, Puzanov, Igor, Bar, Jair, Elon, Yehonatan, Sela, Itamar, Yellin, Ben, Lahav, Coren, Raveh, Shani, Reiner-Benaim, Anat, Reinmuth, Niels, Nechushtan, Hovav, Farrugia, David, Bustinza-Linares, Ernesto, Lou, Yanyan, Leibowitz, Raya, Kamer, Iris, Zer Kuch, Alona |
| Předmět: |
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| Zdroj: |
JCO Precision Oncology; 12/1/2024, Vol. 8, p1-12, 12p |
| Abstrakt: |
PURPOSE: Current guidelines for the management of metastatic non–small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions. PATIENTS AND METHODS: We conducted a multicenter observational trial (ClinicalTrials.gov identifier: NCT04056247) of patients undergoing PD-1/PD-L1 inhibitor–based therapy (n = 540) and an additional patient cohort receiving chemotherapy (n = 85) who consented to pretreatment plasma and clinical data collection. Plasma proteome profiling was performed using SomaScan Assay v4.1. RESULTS: Our test demonstrates a strong association between model output and clinical benefit (CB) from PD-1/PD-L1 inhibitor–based treatments, evidenced by high concordance between predicted and observed CB (R 2 = 0.98, P <.001). The test categorizes patients as either PROphet-positive or PROphet-negative and further stratifies patient outcomes beyond PD-L1 expression levels. The test successfully differentiates between PROphet-negative patients exhibiting high tumor PD-L1 levels (≥50%) who have enhanced overall survival when treated with a combination of immunotherapy and chemotherapy compared with immunotherapy alone (hazard ratio [HR], 0.23 [95% CI, 0.1 to 0.51], P =.0003). By contrast, PROphet-positive patients show comparable outcomes when treated with immunotherapy alone or in combination with chemotherapy (HR, 0.78 [95% CI, 0.42 to 1.44], P =.424). CONCLUSION: Plasma proteome–based testing of individual patients, in combination with standard PD-L1 testing, distinguishes patient subsets with distinct differences in outcomes from PD-1/PD-L1 inhibitor–based therapies. These data suggest that this approach can improve the precision of first-line treatment for metastatic NSCLC. PROphet blood test supports first-line immunotherapy treatment decisions for patients with metastatic NSCLC. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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