Abstract 289P
Background
Human epidermal growth factor receptor 2 (HER2) overexpression/amplification is a potential biomarker for targeted therapy in patients (pts) with biliary tract cancer (BTC). This systematic review describes clinical outcomes in pts with HER2-positive (HER2+) advanced/metastatic BTC and subtypes who had received ≥1 prior therapy.
Methods
Embase®, MEDLINE®, Cochrane, and relevant conferences were searched from database start till 28 Aug 2023 for trials in our population of interest. ROBINS-I was used for quality assessment.
Results
Database searches retrieved 6,611 citations. 12 studies reporting overall or subgroup data for pts with HER2+ BTC were included. All were single-arm, phase (Ph) 1 or Ph 2 trials and ten studies were multicenter. Sample size of pts with HER2+ tumors ranged from 3–80 pts with a median follow-up of 8.1–13 months (mon). Nine therapies (pertuzumab + trastuzumab [P+T], pyrotinib, SHR-A1811, TAS0728, T-deruxtecan [T-DXd], tebotelimab + margetuximab, T+FOLFOX [T+F], tucatinib + T and zanidatamab [zani]) were assessed. HER2+ status was established based on amplification (next generation sequencing [NGS] and/or in situ hybridization [ISH]) and/or overexpression (immunohistochemistry [IHC]) of HER2 and was reported as IHC3+ or IHC3+ and IHC2+/ISH+ or as author defined. Median age range was 62.5–68 years across studies. Where reported, median (95% CI) OS ranged from 7.1 (4.7–14.6) mon (T-DXd) to 10.9 (5.2–15.6) mon (P+T), and median (95% CI) PFS ranged from 3.5 (1.8–6.7) mon (zani, Ph 1) to 5.5 (3.7–7.2) mon (zani, Ph 2). Within trials, survival was better in pts with IHC3+ than IHC2+ or IHC2+/ISH+ tumors. ORR (95% CI) varied from 23% (11–39%, P+T) to 56.3% (T-DXd). Median DOR ranged from 4.9 mon (range:2.1–10.0) (T+F) to 12.9 mon (95% CI, 6.0–NE, zani, Ph 2). Of 12 studies, 2 reported HRQoL data. Treatment related (TR) grade 3-4 adverse events (AE) were reported in 0% (zani, Ph1), 8% (P+T), 39% (T-DXd) and 94% (T+F) pts. TR serious AE were reported in 0% (P+T), 5% (zani, Ph1) and 12% (T-DXd) pts.
Conclusions
HER2 targeted therapies demonstrated promising benefit in patients with previously treated advanced/metastatic HER2+ BTC.
Legal entity responsible for the study
Jazz Pharmaceuticals.
Funding
Jazz Pharmaceuticals.
Disclosure
S. Paisley, A. Ahuja, V. Sharma: Financial Interests, Personal, Full or part-time Employment: Lumanity; Financial Interests, Personal, Other, Consultancy time: Jazz Pharmaceuticals. S. Bowditch, W. Su, J. Sabater, S. Mettam, L. Fan: Financial Interests, Personal, Full or part-time Employment: Jazz Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Jazz Pharmaceuticals. F. Dayyani: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca; Financial Interests, Personal, Invited Speaker: Ipsen, Sirtex, Takeda; Financial Interests, Institutional, Invited Speaker: AstraZeneca, BMS, Bayer, Exelixis, Roche, Ipsen, Signatera, Merck, Taiho.