Abstract 460P
Background
Human epidermal growth factor receptor 2 (HER2) overexpression is present in approximately 25% of patients (pts) with advanced gastroesophageal adenocarcinoma (GEA). Upon progression on first-line therapy (i.e., chemotherapy and anti-HER2 agent), ramucirumab and paclitaxel (rampac) is given in ≥2nd-line setting regardless of HER2 status. We aim to assess whether ramucirumab, an anti-vascular endothelial growth factor receptor 2, is associated with better survival HER2-positive(+) pts compared to those with HER2(-) disease.
Methods
We reviewed all consecutive adult pts with metastatic or unresectable GEA who were treated with rampac for ≥2nd-line therapy at Princess Margaret Cancer Centre (Toronto, Canada) from 2010-2021. Those with an unknown HER2 status and/or start date of rampac were excluded. HER2+ disease was defined as immunohistochemistry (IHC) 3+ or IHC 2+/fluorescence in situ hybridization (FISH)+. Progression free survival (PFS) and overall survival (OS) were defined as time from starting rampac to progression or death and estimated using the Kaplan-Meier method. Cox proportional hazards models were used to analyze associations between patient characteristics and PFS/OS.
Results
In this retrospective cohort of 127 pts who received rampac following progression of first-line chemotherapy +/- anti-HER2 agent, 96 (76%) were male. The age at time of presentation and starting rampac was 59.0 ± 10.3 years and 59.9 ± 10.3, respectively. At the time of diagnosis, 32 (25%) pts were HER2+. The majority of pts (n=99; 78%) received rampac in the 2nd-line setting compared to 28 (22%) pts who received it in the 3rd/4th line setting. The median PFS and OS for HER2+ pts were 3.6 mos and 9.4 mos, respectively, which were similar to HER2- pts (median PFS = 3.6 mos; median OS = 8.2 mos). There was no statistically significant association between HER2 positivity and PFS (adjusted hazards ratio (HR)=0.76, 95% confidence interval (CI) 0.48-1.22, p=0.26), nor OS (adjusted HR=0.88, 95% CI 0.55-1.41, p=0.59).
Conclusions
PFS and OS from ≥2nd-line rampac therapy were similar between HER2+ and HER2- pts. Future studies are necessary to confirm whether temporal changes in HER2 expression are associated with similar outcomes.
Legal entity responsible for the study
The authors.
Funding
Princess Margaret Cancer Foundation.
Disclosure
E. Elimova: Financial Interests, Personal, Invited Speaker: Roche, Daiichi; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: BeiGene, Signatera, AbbVie, Astellas, Viracta Tx; Financial Interests, Institutional, Invited Speaker, Institution receives: Jazz; Financial Interests, Institutional, Invited Speaker: Jazz, Zymeworks, Amgen, AstraZeneca, BMS; Other, A family member employed by Merck Vaccines. All other authors have declared no conflicts of interest.