2023 World Conference on Lung Cancer (Posters)-EP13.05. Early ctDNA Changes and Clinical Outcomes in Extensive Stage Small Cell Lung Cancer Patients on Nivolumab and Temozolomide

EP13.05. Early ctDNA Changes and Clinical Outcomes in Extensive Stage Small Cell Lung Cancer Patients on Nivolumab and Temozolomide - PDF(Slides)

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A study conducted at The Arthur G. James Cancer Hospital and The Ohio State University Comprehensive Cancer Center explored the association between early changes in circulating tumor DNA (ctDNA) and clinical outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC) who were treated with nivolumab and temozolomide. ES-SCLC is characterized by rapidly dividing malignant cells and early widespread metastases. The standard-of-care treatment for ES-SCLC is platinum in combination with etoposide. Although the addition of immunotherapy to chemotherapy has improved median overall survival (mOS) by 2 months, patient outcomes still remain poor, with mOS of 12 months. <br /><br />In this study, 27 patients with relapsed ES-SCLC were treated with nivolumab and temozolomide. Plasma samples were collected before cycles 1 and 2 of treatment and analyzed for genomic alterations using the Guardant360 assay. The changes in ctDNA were evaluated by calculating the ratio of mean variant allele fraction (meanVAF) between pre-treatment and on-treatment samples. <br /><br />The results showed that patients who had a decrease in ctDNA had improved median progression-free survival (mPFS). Early changes in ctDNA were also correlated with subsequent imaging changes. The most common gene alterations detected in the baseline ctDNA analysis were TP53 and RB1 alterations. Mutations in DNA damage response, transcription factors, and cell signaling pathways were also detected. <br /><br />Among the patients who achieved ctDNA reduction from the baseline, the reduction was -61.5%. Early increases and decreases in ctDNA changes correlated with subsequent confirmed and unconfirmed imaging changes. In terms of survival outcomes, patients who had a decrease in meanVAF ctDNA from the baseline had an mPFS of 3.3 months, compared to 1.9 months for patients with an increase in meanVAF ctDNA. However, there was no significant association with mOS. <br /><br />Overall, this study suggests that early changes in ctDNA may have predictive value for clinical outcomes in patients with ES-SCLC treated with nivolumab and temozolomide. Further research is needed to validate these findings and explore the potential of ctDNA as a biomarker for treatment response in ES-SCLC.

Asset Subtitle

Jinesh Gheeya

Meta Tag

Speaker Jinesh Gheeya

Topic SCLC & Neuroendocrine Tumors: NETs

Keywords

ctDNA

ES-SCLC

nivolumab

temozolomide

genomic alterations

mPFS

TP53

RB1

imaging changes

biomarker