Background

Neoadjuvant chemotherapy (NACT) combined with Traztuzumab and Pertuzumab is recommended as treatment of human epidermal growth factor receptor 2 positive (HER2+ve), locally advanced, inflammatory/early-stage breast cancer at high risk of recurrence. Before 2019 Herceptin was the only Traztuzumab drug on patent. Now there are 4 biosimilars available. There is a paucity of neoadjuvant data comparing the efficacy and safety of neoadjuvant Herceptin and its biosimilars. This study aimed to evaluate pathological complete response (pCR) rates and tolerability with the biosimilar Herzuma and Herceptin in combination with neoadjuvant Pertuzumab and chemotherapy in the first UK Cancer Centre to use Herzuma.

Method

61 patients received Pertuzumab+Herceptin/Herzuma as part of their NACT between January 2017 and June 2019. 9 patients were excluded due to failure to complete NACT. The primary endpoints were the percentage of patients who achieved pathological complete response defined as pCR breast and axilla (ypT0/ ypN0). Secondary endpoints were evaluation of tolerability and the relationship between pCR rates and tumour biology.

Results

25 patients received Herceptin (H) and 27 received Herzuma (Hz) and average age was 49 (35-62) and 53 (34-73) respectively. H-group tumour demographics were ≥T2 80%, LN positive 52%, grade 3 64%, ER negative 28%. Hz-group tumour demographics were; ≥T2 85%, LN positive 74%, grade 3 44%, ER negative 52%. ypT0/ ypN0 was achieved in 48% of patients of H-group and 63% of Hz-group. ypT0/ypN0 was more likely if the tumours were grade 3 or ER-negative. Tolerability was similar in both groups with 31% H-group and 30% HZ-group requiring a dose delay. Most common reasons for delay H-group; patient unwell (43%), allergic reaction (29%), patient choice (14%), Hz-group; patient unwell (23%), bone marrow suppression (23%), patient choice (23%). 23% of H-group and 41% of Hz-group required a chemotherapy dose reduction.

Conclusion

When used in combination with Pertuzumab and chemotherapy, neoadjuvant biosimilar Herzuma is comparable to Herceptin in terms of efficacy and safety. The signal of superiority of Herzuma over Herceptin in achieving pCR during NACT is likely due to the non-balanced tumour biology between the groups.  

Impact statement

Confirmation of neoadjuvant efficacy of a biosimilar HER2 targeting drug in breast cancer.