Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

HER2-Directed therapy

6 evidence topics · 6 sources

HER2 alteration frequency and testing in biliary tract cancer

“HER2 alterations, comprising amplifications and mutations, as well as human epidermal growth factor receptor 2 (HER2) protein overexpression, can be found in ∼5%-10% of BTC cases, with a higher prevalence observed in extrahepatic CCA and gallbladder carcinoma.” (opens the source at this quote in a new tab)
“Most clinical trials focus on patients with HER2 overexpression and HER2 amplification, yet there are currently no standardised criteria for assessing HER2 status in BTC and no specific test can be recommended.” (opens the source at this quote in a new tab)

HER2 amplification yield at screening and the assay defining eligibility in HERIZON-BTC-01

“Between Sept 15, 2020, and March 16, 2022, 847 patients were pre-screened for HER2 amplification and 171 (20%) had HER2-amplified tumours, of which 131 (77%) entered study screening and 87 (66%) were enrolled.” (opens the source at this quote in a new tab)
“HER2 gene amplification status was determined by the VENTANA HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems, Tuscon, AZ, USA). HER2 gene status was classified as non-amplified (HER2/Chr17 ratio <2·0) or amplified (HER2/Chr17 ratio ≥2·0).” (opens the source at this quote in a new tab)

Guideline recommendations for HER2-directed therapy after progression

“Zanidatamab is recommended in patients with previously treated HER2-positive disease [III, A; ESMO-MCBS v1.1 score: 3; ESCAT score: I-C; FDA approved, not EMA approved].” (opens the source at this quote in a new tab)
“Trastuzumab deruxtecan should be considered in patients with HER2 overexpression and/or HER2 amplification who have progressed on or are intolerant to prior treatment [III, A; ESMO-MCBS v1.1 score: 3; ESCAT score: I-C; FDA approved, not EMA approved].” (opens the source at this quote in a new tab)
“Zanidatamab is now FDA approved for previously treated, unresectable or metastatic HER2-positive BTC.” (opens the source at this quote in a new tab)

“HER2-directed therapies can be considered in patients with HER2 overexpression/amplification who have progressed on or are intolerant to prior treatment [III, A; ESCAT score: I-C]” (opens the source at this quote in a new tab)

Zanidatamab: HERIZON-BTC-01 phase 2b trial

“Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4-52·8]).” (opens the source at this quote in a new tab)
“The median duration of response for the 33 patients in cohort 1 with a confirmed objective response was 12·9 months (95% CI 6·0–not estimable; range 1·5–16·9+) with 16 (49%) patients having ongoing responses at the time of the data cutoff (figure 2B; appendix p 5). No responses to zanidatamab were observed in cohort 2.” (opens the source at this quote in a new tab)
“The median progression-free survival by independent central review in cohort 1 was 5·5 months (95% CI 3·7–7·2; range 0·3–18·5+; table 2; appendix p 6). Overall survival at 9 months was 69·9% (95% CI 57·8–79·1) for cohort 1; median overall survival data were immature at the time of data cutoff.” (opens the source at this quote in a new tab)
“16 patients (18%) had grade 3 treatment-related adverse events; of these, diarrhoea (four [5%] patients), ejection fraction decreased (three [3%]), and anaemia (two [2%]) occurred in more than one patient. No grade 4 or grade 5 treatment-related adverse events were reported.” (opens the source at this quote in a new tab)

Trastuzumab deruxtecan: DESTINY-PanTumor02 biliary tract cohort and HER2 IHC 3+ population

“In patients with central HER2 IHC 3+ expression (n = 75), the ORR was 61.3% (95% CI, 49.4 to 72.4), the median DOR was 22.1 months (95% CI, 9.6 to not reached), the median PFS was 11.9 months (95% CI, 8.2 to 13.0), and the median OS was 21.1 months (95% CI, 15.3 to 29.6).” (opens the source at this quote in a new tab)
“Grade ≥3 drug-related adverse events were observed in 40.8% of patients; 10.5% experienced adjudicated drug-related interstitial lung disease (ILD), with three deaths.” (opens the source at this quote in a new tab)

Tucatinib plus trastuzumab: SGNTUC-019 biliary tract cancer cohort

“The cORR was 46.7% (90% CI, 30.8 to 63.0), with a disease control rate of 76.7% (90% CI, 60.6 to 88.5).” (opens the source at this quote in a new tab)
“The median duration of response and progression-free survival were 6.0 months (90% CI, 5.5 to 6.9) and 5.5 months (90% CI, 3.9 to 8.1), respectively.” (opens the source at this quote in a new tab)
“At data cutoff, 15 patients (50.0%) had died, and the estimated 12-month overall survival rate was 53.6% (90% CI, 36.8 to 67.8).” (opens the source at this quote in a new tab)