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J. Usher
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-056 - Use of Cell-Free Circulating RNA (cfRNA) Expression of PD-L1 and ERCC1 in Plasma to Monitor Response to Therapy in NSCLC (ID 9038)
09:00 - 09:00 | Author(s): J. Usher
- Abstract
Background:
There is an unmet need to evaluate tumor response by other means than radiology tests. Cell-free circulating tumor RNA (cfRNA) can be extracted from plasma of cancer patients (pts); measuring dynamic changes in gene expression and levels of b-actin; cfRNA (per ml of plasma) as a proxy for total cfRNA in metastatic patients has shown great potential for evaluating disease status and predicting outcome to anti-tumoral therapy in advance of imaging. We have previously shown that high levels of PD-L1 cfRNA expression correlates well with positive response to immunotherapies including nivolumab in pts with NSCLC.
Method:
Blood was drawn from pts at approximately 6-week intervals under various therapies, with CT scans at 3-month intervals. Total cfRNA was extracted from patient plasma and reverse transcribed to cDNA. Levels of b-actin, ERCC1 and PD-L1 were quantitated across multiple blood draws by RT-qPCR and correlated with pt response (PR/SD/PD), as determined by CT scans.
Result:
A total of 24 NSCLC patients were enrolled in a 1-year clinical study. Non-SCC comprised 87% (21/24). 19 pts completed the first two cycles of therapy. 1 pt with PR had decreasing levels of cfRNA, 10 pts achieved SD with decreasing or no change while 6/8 pts with PD had increasing levels of cfRNA. CfRNA levels were predictive of disease status about 4 weeks in advance of imaging in 6/19 pts and matched with disease status in 8/19 pts (74% ). Dynamic changes in PD-L1 expression correlated with response to nivolumab in 3/4 pts. In 2/4 pts with SD, PD-L1 remained undetected after therapy, whereas 1 patient continued to have PD despite loss of PD-L1. PD-L1 was undetectable in a pt initially with PD on nivolumab who achieved SD after one cycle of nivolumab plus radiation. Changing ERCC1 expression correlated with platinum-based therapy outcome in 8/8 patients. 4/4 patients with PD on pemetrexed/carboplatin had an increase in ERCC1. 4/4 patients with lower or decreasing levels of ERCC1 achieved PR or SD. In the only patient achieving PR, ERCC1 became undetectable during treatment.
Conclusion:
We found significant concordance between clinical response and changes in plasma cfRNA levels in NSCLC pts (74%). Levels of PD-L1 expression correlated with response in 3/4 pts treated with nivolumab . ERCC1 levels were predictive of outcome to platinum based therapy for 8/8 patients. ERCC1 and PD-L1 expression in cfRNA can be used to monitor response to platinum-based and immuno-therapy.
