Table 1.
Trials of Newer HER2 Targeted Therapies.
| Trial | Patients and Key Inclusion Criteria | Study Design | Results | Adverse Events |
|---|---|---|---|---|
| Phase III SOPHIA trial [49] |
n = 536 Pre-treated (lines 1–3) HER2+ metastatic BC |
MARG 15 mg/kg q3weeks vs. TRAS 8 mg/kg loading dose followed by 6 mg/kg q3w + investigator’s choice (capecitabine, eribulin, gemcitabine or vinorelbine) |
PFS: (HR 0.76, p = 0.033)-higher PFS if homozygous for CD16A-F allele Median PFS: 5.8 mo (MARG) vs. 4.9 months (TRAS) ORR: 22.1% (MARG) vs. 16.0% (TRAS); p = 0.060 |
Infusion reaction: 12.9% (MARG) vs. 3.8% (TRAS) Adverse events of any grade were similar between MARG and TRAS |
| Phase III ALTERNATIVE Trial, adding lapatinib to herceptin and aromatase inhibitor [50] |
n = 355 Postmenopausal women with HER2+, HR+ MBC (had received prior ET and prior neoadjuvant or first line TRAS + chemo) |
1:1 randomization LAP 1000 mg/d + TRAS (n = 120) + AI vs. LAP 1500 mg/d + AI (n = 118) vs. TRAS + AI (n = 120) AI: letrozole 2.5 mg/d, anastrozole 1 mg/d or exemestane 25 mg/d |
Median PFS: 11.0 mo (LAP + TRAS + AI) vs. 5.7 mo (TRAS + AI) (HR = 0.62, p = 0.0064) vs. 8.3 mo (LAP + AI) (HR = 0.71, p = 0.361) ORR: 31.7% (LAP + TRAS + AI) vs. 13.7% (TRAS + AI) vs. 18.6% (LAP + AI) |
|
| Phase IB HER2 CLIMB (TUC) trial [51] |
n = 60 HER2+ metastatic BC, including patients with untreated or progressive brain metastasis |
Not randomized TUC (300 mg bid) + CAP vs. TUC + TRAS vs. TUC +CAP + TRAS |
RR: 42% (5/12) in patients with brain mets (TUC + CAP +TRAS) ORR: 61% (14/23) in the triple regimen Median duration of response: 11.0 (range, 2.9–18.6) in triplet regimen |
Grade 1–2 in triplet regimen: diarrhea (33%), nausea (26%) and fatigue (15%) Dose-limiting toxicity: grade 4 cerebral edema in a patient with untreated brain metastasis who was not on steroids |
BC, breast cancer; MARG, margetuximab; TRAS, trastuzumab; HR, hormone receptor; MBC, metastatic breast cancer; ET, endocrine therapy; LAP, lapatinib; AI, aromatase inhibitor; ORR, overall response rate; OS, overall survival; PFS, progressive free survival; TUC, tucatinib; CAP, capecitabine; RR, response rates.