Dual Blockade with AFatinib and Trastuzumab as NEoadjuvant Treatment for Patients with Locally Advanced or Operable Breast Cancer Receiving Taxane–Anthracycline Containing Chemotherapy—DAFNE (GBG-70)

Media type: E-Article

Title: Dual Blockade with AFatinib and Trastuzumab as NEoadjuvant Treatment for Patients with Locally Advanced or Operable Breast Cancer Receiving Taxane–Anthracycline Containing Chemotherapy—DAFNE (GBG-70)

Contributor: Hanusch, Claus; Schneeweiss, Andreas; Loibl, Sibylle; Untch, Michael; Paepke, Stefan; Kümmel, Sherko; Jackisch, Christian; Huober, Jens; Hilfrich, Jörn; Gerber, Bernd; Eidtmann, Holger; Denkert, Carsten; Costa, Serban; Blohmer, Jens Uwe; Engels, Knut; Burchardi, Nicole; von Minckwitz, Gunter

imprint: American Association for Cancer Research (AACR), 2015

Language: English

DOI: 10.1158/1078-0432.ccr-14-2774

ISSN: 1078-0432; 1557-3265

Keywords: Cancer Research ; Oncology

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Footnote:

Description: AbstractPurpose: Dual anti-HER2 blockade with trastuzumab/pertuzumab or trastuzumab/lapatinib in combination with anthracycline/taxane–based chemotherapy can reach pathologic complete response (pCR) rates of up to 60% in HER2-positive breast cancer. The DAFNE (Dual blockade with AFatinib and trastuzumab as NEoadjuvant treatment) phase II study (NCT015591477) investigated a dual blockade with the irreversible pan-HER inhibitor afatinib and trastuzumab in this setting.Experimental Design: Participants with untreated, centrally HER2-positive breast cancer were treated for 6 weeks with afatinib (20 mg/d) and trastuzumab [(8) 6 mg/kg/3 weeks] alone; followed by 12-week treatment with paclitaxel (80 mg/m2/1 week), trastuzumab, and afatinib; followed by 12 weeks with epirubicin (90 mg/m2/3 weeks), cyclophosphamide (600 mg/m2/3 weeks), and trastuzumab before surgery. Primary objective was pCR rate, defined as ypT0/is ypN0. We expected a pCR rate of 70%; 65 patients were needed to exclude a rate of ≤55%.Results: pCR rate was 49.2% [90% confidence interval (CI), 38.5–60.1] in 65 treated patients. Patients with hormone receptor–negative (N = 19) or hormone receptor–positive (N = 46) tumors showed pCR rates of 63.2% and 43.5%, respectively (P = 0.153). Patients with (N = 9) or without (N = 56) lymphocyte predominant breast cancer (LPBC) showed pCR rates of 100% and 41.1%, respectively (P &lt; 0.001). PCR rate was not different in patients with or without PIK3CA tumor mutations (P = 0.363). Clinical responses were seen in 96.3% of 54 evaluable patients, and breast conserving surgery was possible in 59.4% of 62 assessable patients. Most frequent nonhematologic grade 3–4 toxicities were diarrhea (7.7%), increased creatinine (4.6%), and infection (4.6%). One patient developed symptomatic congestive heart failure.Conclusions: Neoadjuvant treatment with afatinib, trastuzumab, and chemotherapy showed acceptable tolerability, and a pCR rate comparable with that of other anti-HER2 doublets but below challenging expectations. Clin Cancer Res; 21(13); 2924–31. ©2015 AACR.

Access State: Open Access

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