Pathological complete response rates following different neoadjuvant chemotherapy regimens for operable breast cancer according to ER status, in two parallel, randomized phase II trials with an adaptive study design (ECTO II)

• Published in: Breast cancer research and treatment 2012-04, Vol.132 (3), p.843-851
• Main Authors: Zambetti, Milvia, Mansutti, Mauro, Gomez, Patricia, Lluch, Ana, Dittrich, Christian, Zamagni, Claudio, Ciruelos, Eva, Pavesi, Lorenzo, Semiglazov, Vladimir, De Benedictis, Elena, Gaion, Fernando, Bari, Mario, Morandi, Paolo, Valagussa, Pinuccia, Luca, Gianni
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Adult; Aged; Androstadienes - administration & dosage; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - surgery; Cancer; Cancer research; Cancer therapies; Capecitabine; Chemotherapy; Clinical outcomes; Clinical Trial; Clinical trials; Cyclophosphamide - administration & dosage; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Doxorubicin - administration & dosage; Estrogen; Estrogens; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Leukopenia - chemically induced; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Methotrexate; Methotrexate - administration & dosage; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm, Residual; Neutropenia - chemically induced; Oncology; Paclitaxel - administration & dosage; Product development; Receptors, Estrogen - metabolism; Treatment Outcome; Tumors
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-011-1660-6

Sequential doxorubicin/paclitaxel (AT) followed by CMF treatment was shown to be an active neoadjuvant chemotherapy regimen in the first European Cooperative Trial in Operable Breast Cancer (ECTO I trial). The aim of the current study (ECTO II) is to assess the complete pathological response (pCR) rate following three different anthracycline and taxane-containing neoadjuvant chemotherapy regimens, with or without capecitabine (X). Patients with operable, invasive breast cancer >2.0 cm in diameter, were randomized to AT→CMF, AT→CMX or AC→TX regimens in two parallel, randomized, open-label, phase II trials (within a single study) in patients with estrogen receptor negative (ER−) and estrogen receptor positive (ER+) diseases, respectively. Exemestane was delivered concomitantly with neoadjuvant chemotherapy in ER+ tumors. Achievement of pCR was more common in ER− than ER+ women (45.3 vs. 10.4%). Capecitabine was only associated with a higher frequency of pCR in ER+ patients receiving AT→CMX. Overall response rates (ORR) ranged from 88 to 97%, and this translated into high rates of breast-conserving surgery (67% of ER− patients and 72% of ER+ patients). All three regimens were well tolerated. Febrile neutropenia and gastrointestinal effects were the most common grade ≥3 adverse events. As expected, the ECTO II study showed higher pCR rates in patients with ER− disease. Substituting capecitabine for fluorouracil (± methotrexate) in anthracycline/taxane-containing regimens appeared to be beneficial only in ER+ tumors. Translational studies investigating interactions between therapeutic agents and tumor biology are warranted to refine patient selection and improve the results of neoadjuvant chemotherapy.