Pathological Response and Cardiotoxicity Following Neoadjuvant Dual Anti-HER2 Therapy: Early Experience at a New Cancer Centre.


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Adam Henry1,Gerard Walls1,Goudarz Mazdai1,Linda McLaughlin1,Lucy Jellett1,Rhun Evans2
1NHS (Western Health and Social Care Trust),2NHS (Western and Social Care Trust)

Abstract

Background

Large breast cancer studies (eg NeoSphere) have demonstrated increased pathological complete response (pCR) rates with neoadjuvant systemic therapy including dual anti-HER2 therapy compared with trastuzumab alone. The addition of pertuzumab reportedly does not increase the modest risk of cardiotoxicity associated with trastuzumab (TRYPHAENA). Neoadjuvant systemic therapy is increasingly being adopted for locally advanced and inflammatory disease. The aim of this study was to describe the early real-world experience of neoadjuvant systemic therapy including trastuzumab and pertuzumab amongst patients at a new Cancer Centre in terms of pCR, tolerability and cardiotoxicity.

Method

Patients treated with dual anti-HER2 blockade were identified from a prospective database of neoadjuvant systemic therapy between November 2016 and March 2019 at a tertiary centre. Electronic records were interrogated for information pertaining to treatment, histopathology and complications.

Results

Of our prospective database of 40 patients, 28 were HER2 positive and received treatment with dual anti-HER2 blockade. The cohort had a mean age of 52. A majority of patients had grade III (86%) and ductal carcinoma (86%). Approximately half were clinically node-positive prior to embarking on systemic therapy and 64% were ER-positive. Clinical response was evident in 93% cases by cycle 3. Following a median of 6 cycles, 61% demonstrated pCR. One resected tumour exhibited no evidence of treatment response. One patient experienced cardiotoxicity with a fall in ejection fraction of 13%. Adverse events prompted a one-week deferral in systemic therapy for 4 patients and hospital admission for 12 patients.

Conclusion

Aligning with phase III study results and other small UK institutional series, neoadjuvant systemic therapy including trastuzumab and pertuzumab is tolerable, safe from a cardiac perspective, and is associated with a high pCR rate.