DRL-Trastuzumab was found to have similar efficacy, safety, pharmacokinetics, and immunogenicity as Herceptin in HER2-positive breast cancer patients in a randomized, double-blind study.
Trastuzumab, marketed under the brand name Herceptin, is a standard therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The drug DRL_TZ, a potential trastuzumab biosimilar to Herceptin, was developed to improve affordability.
A randomized, double-blind study conducted by the drug manufacturer evaluated the efficacy, safety, pharmacokinetics, and immunogenicity of DRL_TZ versus Herceptin (reference medicinal product [RMP]) plus paclitaxel in HER2-positive metastatic breast cancer patients. The study’s results were published in the journal JCO Global Oncology.
Participant Characteristics
A total of 164 patients were randomized (1:1) to receive either DRL_TZ or RMP. An additional 44 patients were recruited to the DRL_TZ arm, resulting in 126 patients (82 randomized + 44 non-randomized) in the “pooled test arm”. Demographics and baseline clinical characteristics were balanced between the arms. Most patients were Asian (90.2%).
Statistically Comparable Best Overall Response Rates Observed
In the intention-to-treat (ITT) population, by week 25, complete response was observed in five patients in the DRL_TZ arm and one patient in the RMP arm, whereas a partial response was observed in 40 patients in the DRL_TZ arm and 37 in the RMP arm. Two patients in the DRL_TZ arm and three in the RMP arm showed stable disease. Similar results were observed in the full analysis set/modified ITT (FAS/mITT) and per protocol (PP) populations.
Primary efficacy analysis revealed the best overall response rate (ORR) of 91.9% (93.3% confidence interval: 83.2–96.3) in the DRL_TZ arm (n=62) and 82.1% (93.3% CI: 72.0–89.1) in the RMP arm (n=67) in the PP population; the between-arm difference in proportion was 9.8%. The ITT and FAS/mITT populations showed similar results.
Comparable Progression-Free Survival and Disease Control Rate Observed
Progression-free survival (PFS) at 6 months was observed in 85.4% of patients in the DRL_TZ arm and 70.9% in the RMP arm in the PP population; the between-arm difference was 14.5%. The disease control rate (DCR) in the PP population was 96.8% in the DRL_TZ arm and 91% in the RMP arm; the between-arm difference was 5.7%. Overall comparable data was observed in the randomized and pooled DRL_TZ patients for best ORR, PFS, and DCR.
Similar Safety Profiles
Treatment-emergent adverse events (TEAEs) were reported in 155 patients, including 78 (95.1%) in the DRL_TZ arm and 77 (93.9%) in the RMP arm. The most common TEAEs were anemia, asthenia, alopecia, diarrhea, peripheral neuropathy, leukopenia, pyrexia, cough, and pain. In total, 34 serious adverse events (SAEs) were reported in 23 patients, including 20 SAEs in 15.9% of DRL_TZ arm patients and 14 in 12.2% of RMP arm patients. There were three fatal events (not related to the study drug). Grade ≥3 TEAEs occurred in 36.6% and 40.2% of patients in the DRL_TZ and RMP arms, respectively. Six, three, and ten patients experienced cardiac toxicity in the DRL_TZ, RMP, and pooled test arms, respectively.
Comparable Pharmacokinetics and Immunogenicity
The trastuzumab pharmacokinetic parameters were comparable between the treatment arms, with no statistically significant differences. The incidence of antidrug antibodies was low and comparable in both arms, with no neutralizing antidrug antibodies observed.
Source:
Reddy, N. C., Reddy, P., Ranpura, A., Maharaj, N., Arora, R. S., Mamillapalli, G., Adhav, A., Diwan, A. K., Manikhas, A., & Krasnozhon, D. (2024). Efficacy, safety, pharmacokinetics, and immunogenicity of DRL-Trastuzumab versus herceptin in human epidermal growth factor receptor 2–Positive metastatic breast cancer: a randomized controlled trial. JCO Global Oncology, 10. https://doi.org/10.1200/go.22.00328
