Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.
e18109 Background: The main immunotherapy (IMMUNO) trials that led to the approval of these agents for non-small cell lung cancer (NSCLC) accrued a minimum number of Hispanic (HISP) patients (pts) or, in some studies, no HISP pts at all. Additional data is thus needed to validate outcomes in HISP pts with NSCLC treated with IMMUNO. While it is known that genomic profiles and cancer survivals are different between HISP, Non-Hispanic Whites (NHW), and African-Americans; no study has yet looked at differences in IMMUNO outcomes between these populations. Methods: We present data in 436 NSCLC pts treated with IMMUNO at 5 large institutions (3 in the US, 2 in Latin America). The agents evaluated include: nivolumab, pembrolizumab and atezolizumab. 256 pts were HISP and 180 pts were NHW. Most of the pts were treated with single agent therapy as second line (or beyond) while a small group of pts were treated as first line. The primary endpoints of the study were: response rate (ORR), progression free survival (PFS) and overall survival (OS). Results: Among NHW pts, disease control rate (DCR) was 67% for Adenocarcinomas (Adeno) and 46% for squamous cell carcinomas (SQCC). In HISP pts there were no differences in DCR rates between both histologies: 68% for Adeno and 67% SQCC. There were no statistical significant differences among HISP and NHW pts regarding ORR, PFS, OS, and responses according to PD-L1 status. Conclusions: This is the largest publication and comparison of NSCLC immunotherapy outcomes in HISP vs NHW pts. No significant differences were found in the clinical outcomes between these 2 ethnic groups despite expected genomic differences. Pts with actionable mutations were excluded as they usually do not get IMMUNO as first or second line; an approach that might change after IMPOWER 150. These results are comparable to the ones seen in Checkmate and Keynote studies. As expected, higher response rates were seen in first line therapy and pts with PD-L1 (+) status. Further comparisons will be better addressed by a larger prospective study.[Table: see text]
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