Abstract 417P
Background
Rechallenge with EGFR inhibitors represents a promising strategy for patients (pts) with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy driven anti-EGFR rechallenge in a RAS and BRAF WT selected population.
Methods
CRC pts with RAS and BRAF WT profile both on tumour tissue at diagnosis and on ct-DNA at baseline receiving rechallenge with anti-EGFR based regimens were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing (PyroMark Q24 MDx Workstation) and nucleotide sequencing (Genetic Analyzer ABI3130) assays. Real-time PCR (Idylla) and droplet digital PCR (QX200 System) were performed to confirm the RAS-BRAF mutational status. Several clinical variables were evaluated in relation to outcome. Statistical analysis was performed with MedCalc package version 14.10.2.
Results
A total of 26 pts receiving anti-EGFR rechallenge between July 2018 and February 2021 were included in our analysis. In the global population ORR was 25.0%, mOS was 5.0 months, mPFS was 3.5 months. Long anti-EGFR free interval, previous response to anti EGFR therapy and >2 previous lines for metastatic disease were associated with improved clinical outcome at univariate analysis. Prior responders with longer anti- EGFR free interval experienced the best clinical outcome (Table). In a multiple logistic regression model only the anti-EGFR free interval was confirmed to be a significant predictor for mOS (p:0.033) and mPFS (p:0.020). Table: 417P
| ORR | p | PFS (months) | HR | p | OS (months) | HR | p | |
| Anti-EGFR free interval >14 months ≤14 months | 36.4% 13.3% | 0.350 | 7.0 3.0 | 0.27 | 0.013 | 13.0 5.0 | 0.28 | 0.019 |
| Previous response to anti-EGFR prior responsers prior non-responders | 25.0% 16.7% | 1.000 | 5.0 2.0 | 0.26 | 0.048 | 7.0 5.0 | 0.57 | 0.333 |
| Prior responders+anti-EGFR free interval>16 months yes no | 57.1% 10.5% | 0.027 | not reached 3.0 | 0.14 | 0.0003 | not reached 5.0 | 0.30 | 0.026 |
| Previous lines for metastatic disease 2 >2 | 0.0% 25.0% | 1.000 | 1.0 4.0 | 0.05 | 0.041 | 1.0 7.0 | 0.045 | 0.034 |
Conclusions
The liquid biopsy driven rechallenge strategy with anti-EGFR confirmed to be feasible in clinical practice. The clinical outcome resulted consistent with the literature data. In addition to the molecular selection through the analysis of ct-DNA for RAS, the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Marco Puzzoni MD PhD.
Funding
Has not received any funding.
Disclosure
G. Palmieri: Financial Interests, Institutional, Advisory Board: BMS; MSD; Financial Interests, Institutional, Invited Speaker: Roche; Pierre-Fabre; Novartis; Incyte. All other authors have declared no conflicts of interest.