Abstract 85P
Background
HER2+ mCRCs, displaying HER2 overexpression or ERBB2 amplification, represent a rare molecular subset, accounting for 2- 6%. Recently, its role as a potential actionable target has emerged, with promising results in refractory mCRC. Despite that, nowadays HER2 testing is not routinely included in the diagnostic workup of mCRC.
Methods
This is an observational, retrospective, multicenter study, aiming to describe features and prognostic value of HER2+ mCRCs from real world pts. Pts with mCRC tested for HER2 status who received at least one line of therapy (tx) at 11 Italian Institutions within the Lazio Region between Mar2011 and Jan2024 were enrolled. HER2 status was assessed either for HER2 overexpression using IHC according to the HERACLES diagnostic criteria or for ERBB2 amplification using NGS. Differences between groups were compared using the Chi Square test. Endpoint for prognostic assessment was OS. Endpoints for predictive assessment were PFS, RR and DCR. Statistical significance was set at p .05.
Results
495 pts were included, of those 57 pts had a HER2+ mCRC (11.5%). HER2 positivity was more frequent among tumors with RASwt compared to RASmt (14.6 vs 8.5%; p .03), lung mts (p .04), synchronous metastatic disease (p .03), lymph node mts (p.02), brain mts (p.01) and liver mts (p.004). No correlation with primary tumor location (PTL) was observed (p .2). At a median FU of 19.2 months, OS did not significantly differ according to HER2 (p .1). 127 pts with RASwt mCRC (109 HER2- and 18 HER2+) received an antiEGFR-based first-line tx. PFS was significantly shorter (p .01) and RR was lower for HER2+ tumors (p .003), while no difference was observed for DCR (p .3). Of 57 HER2+ tumors, 12 received an antiHER2 tx (9 were RASwt and 3 RASmt), with RAS status not significantly impacting on antiHER2 activity.
Conclusions
We showed that HER2+ mCRCs are more frequently, though not exclusively, RASwt, and display a specific mts tropism. No association with PTL was observed. HER2 does not impact on prognosis while confirms as negative predictor for antiEGFR tx. Target actionability seems to be retained irrespective of RAS status. The baseline molecular workup of mCRC must include HER2 assessment, irrespective of RAS mutational status and primary tumor location.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.