2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.24. Plasma PCSK9 Levels in Patients Receiving Neoadjuvant Pembrolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC)

P1.24. Plasma PCSK9 Levels in Patients Receiving Neoadjuvant Pembrolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC)

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A study by researchers from the Duke Cancer Institute and Cleveland Clinic Cancer Center investigated the levels of PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) in patients receiving neoadjuvant and adjuvant pembrolizumab therapy for resectable non-small cell lung cancer (NSCLC). The study aimed to understand the resistance mechanisms to neoadjuvant immunotherapy and identify potential predictive or prognostic biomarkers.<br /><br />The researchers conducted a single-arm, phase II study of neoadjuvant and adjuvant pembrolizumab therapy in patients with stage IB, II, or IIIA NSCLC. Blood specimens were collected at designated timepoints, and plasma PCSK9 levels were measured using a colorimetric ELISA assay.<br /><br />The results showed that plasma PCSK9 levels tended to be lower in patients with a major pathologic response (MPR) compared to suboptimal responders (SOR). At collection time 3, there was a significant difference in mean plasma PCSK9 level between MPR and SOR patients. Plasma PCSK9 levels were found to increase following exposure to neoadjuvant pembrolizumab in all patients on the study.<br /><br />The study suggests that patients who experienced a major pathologic response to neoadjuvant treatment tended to have lower plasma PCSK9 levels after surgical resection. The researchers plan to investigate whether increased PCSK9 levels serve as a resistance mechanism to anti-PD1 therapy.<br /><br />Furthermore, future efforts will involve analyzing plasma PCSK9 levels throughout the course of therapy in patients with metastatic NSCLC treated with taxane chemotherapy, ipilimumab, and nivolumab. The researchers also plan to correlate clinical outcomes, genomic analysis, and serum PCSK9 levels.<br /><br />The findings of this study provide insights into the relationship between PCSK9 levels and response to neoadjuvant immunotherapy in patients with NSCLC. More clinical trials are underway to validate and extend these findings, including combining ICI therapy with anti-PCSK9 therapy.

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Cameron Wood, Duke University Health System, United States

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Speaker Cameron Wood, Duke University Health System, United States

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Keywords

Duke Cancer Institute

Cleveland Clinic Cancer Center

PCSK9

Proprotein Convertase Subtilisin/Kexin Type 9

neoadjuvant therapy

adjuvant therapy

non-small cell lung cancer

NSCLC

immunotherapy

predictive biomarkers