medwireNews: The trastuzumab biosimilar HD201 has demonstrated equivalence to the referent drug with respect to total pathologic complete response (pCR) following neoadjuvant treatment in women with HER2-positive early breast cancer, report the TROIKA investigators.
They add that confirmation of the relationship between pCR, an early measure of efficacy, and survival outcomes “will be reassuring and [will] be reported when a longer follow-up will allow reliable estimation.”
In the phase 3 trial, 474 women with a new diagnosis of stage II–III disease were randomly assigned to receive eight cycles of neoadjuvant HD201 or referent trastuzumab 6 mg/kg every 3 weeks (initial loading dose of 8 mg/kg) alongside chemotherapy. The latter consisted of four cycles of docetaxel 75 mg/m2 followed by four cycles of epirubicin 75 mg/m2 plus cyclophosphamide 500 mg/m2. Participants also received 10 cycles of adjuvant HD201 or referent trastuzumab as per the random assignment after surgery.
The locally assessed total pCR rate – evaluated at time of surgery – was 45.0% for the 238 participants who received HD201 and 48.7% for the 236 given referent trastuzumab. This gave a nonsignificant between-group difference of –3.8%, with a 95% confidence interval (CI) of −12.8% to 5.4%, “which fell within the predefined equivalence margin of −15% to 15%,” say the researchers.
The unadjusted ratio of the total pCR rates between the two treatment arms was 0.92, they add in JAMA Oncology.
The findings were similar by central assessment, with total pCR rates of 49.8% and 51.9% in the HD201 and referent trastuzumab groups, respectively, and a difference of –2.1% (95% CI, −11.6% to 7.5%), which was also within the equivalence margin. And the unadjusted ratio of the total pCR rates was 0.96.
Xavier Pivot, from the Institute of Cancer Strasbourg in France, and team note that “[t]he results regarding [breast] pCR, overall response, and response based on mammography, ultrasonography, or clinical tumor evaluations supported the comparable efficacy between HD201 and referent trastuzumab.”
Over the entire treatment period, including the neoadjuvant and adjuvant phases, treatment-emergent adverse events (TEAEs) “were as expected for this population and class of drug,” say the study authors. Serious TEAEs occurred in 9.6% of patients in the HD201 arm and 6.7% of those in the referent trastuzumab arm, and a respective 6.4% and 4.8% discontinued the study drug due to any TEAEs.
TEAEs of special interest for trastuzumab were observed in 88.0% and 84.5% of the HD201 and referent trastuzumab groups, respectively, during the total treatment period, with left ventricular ejection fraction declines to below 50% occurring in a corresponding 3.7% and 1.2%.
Pivot and colleagues summarize that “[t]his phase 3 study demonstrated the equivalence between HD201 and referent trastuzumab in terms of efficacy for the [total] pCR end point and safety.”
And they conclude: “These results support the application submitted for registration of HD201 as a biosimilar of trastuzumab.”
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