Table 2 Dose adjustment criteria
NCI CTCAE 5.0 | Management (after active treatment and observation) | Dose adjustment after the study drug is continued |
|---|---|---|
Pyrotinib | ||
 Clinically significant grade ≥ 2 declined LVEF or LVEF lower than the lower limit of normal (including LVEF declining ≥10% and LVEF < 50% without symptoms, or heart failure) | Discontinue pyrotinib |  |
 Grade 4 diarrhea | Discontinue pyrotinib |  |
 Grade 3 diarrhea or grade 1–2 diarrhea with concomitant symptoms (including but not limited to mild to severe abdominal cramps, grade ≥ 2 nausea or vomiting, declined ECOG performance status, fever, pyemia, decreased neutrophil count, bleeding or dehydration) | Interrupt pyrotinib until diarrhea is restored to grade 0–1 and concomitant symptoms disappear | 80 mg reduction each time to the minimum dose of 240 mg |
 Grade ≥ 2 non-hematologic AEs (except for alopecia, fatigue and asthenia) | Interrupt pyrotinib until diarrhea is restored to grade 0–1 | 80 mg reduction each time to the minimum dose of 240 mg |
 Grade ≥ 3 hematologic AEs | Interrupt pyrotinib until diarrhea is restored to grade 0–1 | 80 mg reduction each time to the minimum dose of 240 mg |
Thalidomide | ||
 Constipation, somnolence, or peripheral neuropathy | Consider interrupting thalidomide | Dose can be reduced as per investigator’s discretion |
 Grade 3–4 AEs or clinically significant symptoms | Consider interrupting or discontinuing thalidomide | Dose reduction can be considered |
 Angioedema, allergic reaction, grade 4 rash, skin peeling, bullae, or any other severe skin reaction | Discontinue thalidomide |  |