P-198 Clinical characteristics of metastatic colorectal cancer with EGFR amplification: A single-center experience

EGFR amplification ( EGFR amp) has been reported in 1-4% of metastatic colorectal cancer (mCRC) patients (pts), but its prognostic and predictive value has not been addressed well so far. Recently better prognosis with favorable clinicogenomic features was known to be associated with EGFR amp (Randon et al, JNCI 2021). Pts with mCRC who underwent next-generation sequencing through a targeted 343-gene panel (AMC Oncopanel, designed through SureDesign in Asan Medical Center) from January 2016 to December 2021 were identified from the electronic medical records. Their EGFR copy numbers processed with CNVkit were screened and the cases with at least 5 EGFR copies were reviewed to adjust to corrected tumor purity that was inferred from variant allelic fraction pattern. Pts whose adjusted copy number ≥6 were defined to be EGFR -amplified ( EGFR amp+) and their clinical characteristics were compared with those without EGFR amp ( EGFR amp-). Among 2,421 pts, 35 pts (1.4%) were EGFR amp+ (the median of copy number = 7, range 6 - 363 ). 33 (94%) were RAS and BRAF V600E wild-type(wt), while 2 had KRAS mutations. All 35 pts were microsatellite-stable (MSS), while 78 out of 2,386 EGFR amp- (3.3%) showed microsatellite instability. Clinical characteristics were not significantly different according to the presence of EGFR amp, but EGFR amp+ tended to have fewer peritoneal seeding at presentation (8.6% v. 21.8%, p = 0.059). Overall survival (OS) tended to be better with EGFR amp+ (median OS 76 months, 95% confidence interval (CI) 28-90) than EGFR amp- (median OS (mOS) 37 months, 95% CI 35-39) but the difference did not reach statistical significance (p = 0.151, adjusted hazard ratio (HR) = 1.16, 95% confidence interval 0.67 – 2.01). Among 523 pts with RAS / BRAF wt tumors who received anti-EGFR antibody-based chemotherapy (anti-EGFR CTx) in their course of diseases, mOS was significantly better in 16 EGFR amp+ pts with 79 months (95% CI 37-120) than 40 months (95% CI 36-43) in 507 EGFR amp- pts (p =0.032, adjusted HR = 2.07, 95% CI 0.98-4.61). Only 7 out of 33 EGFR amp+ RAS / BRAF wt pts were given front-line anti-EGFR CTx, and their progression-free survival (PFS) did not differ from the PFS of 331 pts with EGFR amp- RAS / BRAF wt treated with anti-EGFR CTx (20 vs 14 months, p = 0.416). EGFR amp+ in mCRC was enriched in RAS / BRAF wt MSS tumors and was associated with infrequent peritoneal seeding. The prognostic impact of EGFR amp was prominent in anti-EGFR CTx-treated pts, but the benefit from front-line anti-EGFR Ab in this group was not notable in our cohort.