Table 5.
Summary of clinical trials evaluating the safety and efficacy of approved trastuzumab biosimilars in patients with HER2+ breast cancer.
| Ref. | Chemotherapy Regimens | Cohort Size | Phase | Settings | Endpoints | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| %Ctrough, μg/mL |
%ORR | %EFS | PFS, %HR |
OS, %HR |
%bpCR | DFS, %HR |
TTD, mo | AEs/SAEs | |||||
| [24] Pivot et al., 2018 |
Neoadjuvant phase (8 cycles): SB3 (n = 402) vs. TRZ (n = 398) plus chemotherapy (docetaxel -> FEC) Adjuvant phase (10 cycles) of SB3 or TRZ as monotherapy |
800 | III | Patients with HER2+ early breast cancer in the neoadjuvant setting | 96.3% vs. 91.2% |
51.7% vs. 42.0% |
45.8% vs. 35.8 % | 96.6% (SB3) vs. 95.2% (TRZ) of patients experienced one or more AEs SAEs: 10.5% (SB3 group) vs. 10.7% (TRZ group) 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively |
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| [25] Pivot et al., 2019 |
SB3 (n = 186) vs. TRZ (n = 181) |
367 | III (follow-up) | Patients who completed the phase 3 study | (at 3 years): 91.9% with SB3 and 85.2% with TRZ | Total AEs: 9.1% with SB3 and 17.1% with TRZ Incidence of asymptomatic significant LVEF decrease was rare (SB3, n = 1; TRZ, n = 2) No cases of symptomatic CHF or other cardiac events were reported |
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| [27] Stebbing et al., 2017 |
Neoadjuvant CT-P6 (n = 271) vs. TRZ (n = 278) plus docetaxel (Cycles 1–4) ->FEC (cycles 5–8) |
549 | III | Women ≥ 18 yrs with stage I–IIIa operable HER2+ breast cancer | 46.8% vs. 50.4% | Serious TEAEs: 7% in CT-P6 group vs. 8% in TRZ group (febrile neutropenia) Grade 3 or worse TEAES: 6% in the CT-P6 group vs. 8% of 278 in the TRZ group |
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| [31] Esteva et al., 2019 | CT-P6 (n = 271) vs. TRZ (n = 278) | 549 | III (post hoc analysis) | Female aged over 18 yrs with pathologically confirmed, newly diagnosed, operable HER2+ Breast cancer | Comparable between the two groups regardless of age, region, or clinical disease stage | Similar results with bpCR | Drug-related TEAEs: 47.6% (CT-P6) vs. 52.2% (TRZ) | ||||||
| [32] Stebbing et al., 2021 |
CT-P6 (n=259) vs. TRZ (n=269) |
III (follow-up) |
528 | Post-treatment follow-up from Phase III equivalent study | 1.31 (95% CI: 0.86–2.01) | 1.10 (95% CI: 0.57–2.13) | 1.23 (95% CI: 0.78–1.93) |
Study drug-related cardiac disorders (CT-P6: 8.1% vs. TRZ: 8.6%) Immunogenicity was similar between groups |
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| [43] von Minckwitz et al., 2018 |
Anthracycline-based chemotherapy-> ABP 980 (n = 364) or TRZ (n = 361) |
III | 725 | Women ≥ 18 yrs with histologically confirmed HER2+ invasive early breast cancer, ECOG (0 or 1) in the neoadjuvant setting | 48% vs. 41% | Neoadjuvant phase: Grade 3 or worse AEs: 15% vs. 14% (neoadjuvant phase), 9% and 6% (adjuvant phase) in the ABP 980 and TRZ group, respectively Neutropenia: 21 (6%) patients in both groups |
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| [47] Li et al., 2022 |
PF-05280014 (n = 352) vs. TRZ (n = 355) plus paclitaxel |
III | 707 | Women ≥ 18 yrs with metastatic, histologically confirmed HER2+ breast cancer (ECOG status: 0–2) | 92.9% (95% CI: 0.656–1.316) |
12.25 vs. 12.06 | Incidences of TEAEs overall (98.6%; 96.6%) and for grades ≥3: 41.0%; 43.1%) in PF-05280014 and TRZ group, respectively |
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| [48] Lammers et al., 2018 | PF-05280014 (n = 114) vs. TRZ (n = 112) |
III | 226 | Women older than 18 yrs with histologically confirmed HER2+ breast cancer | 92.1% vs. 93.3% | 47.0% vs. 50.0% | Grade 3–4 TEAEs: 38.1% vs. 45.5%, Antidrug antibody rates: 0% vs. 0.89% | ||||||
| [49] Rugo et al., 2021 |
Trastuzumab dkst (n = 230) vs. TRZ (n = 228) plus taxane -> continued monotherapy until disease progression |
III | 458 (ITT population) 343 (monotherapy/safety population |
Patients with HER2+ mBC | 35.7% vs. 37.7% | 52.6% vs. 50.0% | Cumulative TEAEs and SAEs were similar in both groups, with few grade ≥ 3 TEAEs (69.3% vs. 72.6%), Immunogenicity was low and similar in both groups at 48 weeks |
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TRZ: trastuzumab, EFS: Event-Free Survival, PFS: Progression-Free Survival, DFS: Disease-Free Survival, TTD: Time to Treatment Discontinuation, bpCR: Breast Pathological Complete Response, FEC: Fluorouracil, Epirubicin, Cyclophosphamide, mBC: Metastatic Breast Cancer.