1. Enhertu or Trastuzumab-deruxtecan should be stopped when there is evidence of grade 1 ILD. DLCO should be done at baseline. Symptomatic ILD is at least grade 2. XRay or CT e/o ILD should prompt initiation of steroids. This is in contrast to ILD with checkpoint inhibitors.
2. Neratinib is approved in adjuvant and metastatic setting. At this point unclear if any the benefit in patients treated with pertuzumab and TDM1 in the adjuvant setting. Neratinib may be useful in ERBB2 mutated ( not amplified disease).
3. Tucatinib in the HER2 CLIMB study showed efficacy in both untreated and treated CNS mets with respect to PFS.
Quoted below from NEJM Feb 2020:
Overall survival at 2 years was 44.9% in the tucatinib-combination group and 26.6% in the placebo-combination group (hazard ratio for death, 0.66; 95% CI, 0.50 to 0.88; P=0.005), and the median overall survival was 21.9 months and 17.4 months, respectively. Among the patients with brain metastases, progression-free survival at 1 year was 24.9% in the tucatinib-combination group and 0% in the placebo-combination group (hazard ratio, 0.48; 95% CI, 0.34 to 0.69; P<0.001), and the median progression-free survival was 7.6 months and 5.4 months, respectively. Common adverse events in the tucatinib group included diarrhea, palmar–plantar erythrodysesthesia syndrome, nausea, fatigue, and vomiting. Diarrhea and elevated aminotransferase levels of grade 3 or higher were more common in the tucatinib-combination group than in the placebo-combination group.
4. Margetuximab is approved in combination with chemo, however, the benefits were very modest ( less than a month in PFS) compared to Herceptin with chemo. The benefits were primarily in those with low-affinity CD16A-158F -genotypes.
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