Strength of Anti-HER2 Therapy Combination Is Further Validated in Asian Population

In Asian patients with nonmetastatic HER2-positive early breast cancer, neoadjuvant pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) demonstrated significant benefit, with 88.5% of patients originally deemed to have inoperable tumors proceeding to radical operations with clear resection margins. These data were reported at the 12th European Breast Cancer Conference (EBCC 12) held virtually on October 2 through 3, 2020.¹

“Neoadjuvant [pertuzumab/trastuzumab] was associated with a pCR [pathologic complete response] rate of 58.4% in our Asian cohort,” said the study investigators. “Results in locally advanced disease were promising.”

Although the dual HER2 blockade combination is now considered a standard regimen for the treatment of patients with HER2-positive early-stage breast cancer, there are limited efficacy data regarding the use of the regimen in Asian populations. Patients with pretreatment stage II or III, HER2-positive tumors were included in this multicenter, retrospective study to determine the efficacy of the pertuzumab plus trastuzumab combination in an Asian population.

Results of the phase 2 NeoSphere trial (NCT00545688) of 417 patients with HER2-positive operable, locally advanced, inflammatory, or early stage breast cancer demonstrated the superiority of neoadjuvant pertuzumab plus trastuzumab/docetaxel versus the trastuzumab/ docetaxel doublet. Corresponding rates of pCR were 45.8% and 29.0%. These data were published in 2012 in The Lancet Oncology and served as the basis for the approval of the triplet combination as neoadjuvant therapy for people with high-risk, HER2-positive early-stage breast cancer.^2,3

Overall, 197 patients who had radical surgery following neoadjuvant trastuzumab plus trastuzumab were included in the analysis, 115 of whom experienced a pCR. Patients with hormone receptor–negative disease (n = 65) experienced a high rate of pCRs at 70.8%. About half of the 132 patients with hormone receptor–positive disease (52.3%) experienced a pCR. The association of pCR in patients with hormone receptor–negative versus hormone receptor– positive disease was significant (P = .014).

Patients with locally advanced disease (n = 78) experienced a pCR rate of 52.6%. Rates of pCR were consistent regardless of patients’ prescribed chemotherapy regimen, including doxycycline/carboplatin (57.1%), paclitaxel/carboplatin (67.9%), or doxorubicin/cyclophosphamide followed by doxycycline/carboplatin (53.8%).

Initially, there were 78 patients with locally advanced inoperable disease, 41 (52.6%) of whom experienced a pCR. Sixty-nine patients who were initially not eligible for surgery went on to have radical operation with clear margins.

Patients (n = 211) treated in the study, who were from 6 oncology centers in Hong Kong, received neoadjuvant pertuzumab/trastuzumab from January 2013 to June 2019. In total, 14 patients were not included in the pCR analysis: 7 refused operation and 7 had persistent inoperable or progressive disease.

More than half of patients (57.3%) included in the study had stage III disease. More patients had hormone receptor–positive status (63.5%). The most frequently used concomitant chemotherapy regimen was doxycycline plus carboplatin (78.2%), followed by paclitaxel plus carboplatin (15.6%), then doxorubicin/cyclophosphamide followed by doxycycline/carboplatin (6.2%). The median number of cycles of neoadjuvant pertuzumab was 6 (range, 4-8).

_References:

_{1. Chan WLW, Kwok C, Soong I, et al. Efficacy and safety of neoadjuvant pertuzumab, trastuzumab and chemotherapy in non-metastatic HER2-positive breast cancer in the Asian population: a multicentre analysis. Eur j Cancer. 2020;138(suppl 1):S123-S1234. doi:10.1016/S0959- 8049(20)30870-4}

_{2. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. doi: 10.1016/S1470-2045(11)70336-9}

_{3. FDA grants Roche’s Perjeta accelerated approval for use before surgery in people with HER2-positive early stage breast cancer. News release. Roche. October 1, 2013. Accessed October 21, 2020. https://bit.ly/3m2ptay}