Three different regimens are recommended by the panel as options for subsequent treatment of mCRC with HER2 amplifications: famtrastuzumab deruxtecan-nxki (T-DXd) monotherapy or trastuzumab in combination with either pertuzumab or lapatinib.

Using a ctDNA assay, HER2-amp was detected in 36% of patients with tissue HER2-positive BTC. Those with HER2-amp in ctDNA than HER2-positive in tissue had potentially higher cORR and longer survival with TDXd.

Pts with centrally confirmed HER2-expressing, RAS–wild type mCRC that progressed on ≥ 2 prior regimens received T-DXd 6.4 mg/kg every 3 weeks (q3w) in 3 cohorts (A: HER2 IHC 3+ or IHC 2+/ISH+; B: IHC 2+/ISH−; C: IHC 1+)...The confirmed ORR was 45.3% (24/53 pts; 95% CI, 31.6%-59.6%) in cohort A, including 1 CR and 23 PRs; median DOR was not reached (95% CI, 4.2 mo-NE). The ORR in pts with prior anti-HER2 treatment was 43.8% (7/16 pts; 95% CI, 19.8%-70.1%). The DCR was 83.0% (44/53 pts; 95% CI, 70.2%-91.9%); median PFS was 6.9 mo (95% CI, 4.1 mo-NE); median OS was not reached. No responses were observed in cohorts B or C.