1. Total pathological complete response was not significantly different between trastuzumab and HD201.
2. HD201 has a comparable safety profile to trastuzumab.
Evidence Rating Level: 1 (Excellent)
Study Rundown: This study aimed to compare trastuzumab to HD201 in the treatment of ERBB2-positive (HER2) early breast cancer. Outcome measures of interest included total pathological complete response (tpCR), as well as safety. The absence of malignant cells in breast and axillary lymph node specimens from surgery was considered as tpCR. The tpCR for trastuzumab was 48.7% and was 45% for HD201. For the per-protocol analysis set (PPS), the results were 51.9% and 49.8%, in the trastuzumab and HD201 groups, respectively. There were 250 treatment-emergent adverse effects (TEAEs) in the HD201 group, and 247 TEAE in the trastuzumab group. Serious TEAEs were noted in 24 and 17 patients, in the HD201 and trastuzumab groups, respectively. TEAEs included cardiotoxic effects as well as developing anti-trastuzumab antibodies. 7 patients in the HD201 and 6 in the trastuzumab group developed anti-trastuzumab antibodies. A left ventricular ejection fraction (LVEF) value of less than 50% developed in 9 HD201 patients and 3 trastuzumab patients. Limitations to this study include a short follow-up period. Overall, HD201 is equivalent to and has potential as a biosimilar medication to referent trastuzumab for the treatment of ERBB2-positive early breast cancer.
Relevant Reading: Can we establish a hierarchy among trastuzumab biosimilar candidates?
In-Depth [randomized controlled trial]: This multi-centre, international, double-blind, randomized clinical equivalence trial enrolled and randomly assigned adult patients with ERBB2-positive breast cancer to receive either trastuzumab or HD201. The modified full analysis set included 502 patients who received at least 1 dose of medication during the study; 252 in the trastuzumab group, and 250 in the HD201 group. Of these, 474 met inclusion criteria for the per-protocol analysis set (PPS) (238 in the HD201 group, 236 in the trastuzumab group). The primary study outcome of total pathological complete response (tpCR) was 45% for biosimilar HD201, and 48.7% for referent trastuzumab, with no significant difference between the two (-3.8%; 95% confidence interval (CI), -12.8% to 5.4%). For the PPS, the results were 51.9% and 49.8%, in the trastuzumab and HD201 groups, respectively. This was a -2.1% difference (95% CI, -11.6% to 7.5%). Safety results were as follows: 250 patients in the HD201 group experienced TEAEs, while 247 in the trastuzumab group did. Serious TEAEs were reported in 24 (HD201) and 17 (trastuzumab) patients. Adverse events included a reduced LVEF of <50% (9 of the HD201 patients, 3 of the trastuzumab patients), as well as the development of anti-trastuzumab antibodies (7 HD201 patients, 6 trastuzumab patients). Of the HD201 group, 16 patients discontinued the study due to TEAEs, while 12 in the trastuzumab group did.
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