Dual blockade with Afatinib and trastuzumab as Neoadjuvant treatment for patients with locally advanced or operable breast cancer receiving taxane-anthracycline containing chemotherapy
Mené sur 65 patientes atteintes d'un cancer du sein HER2+, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse pathologique complète, et la toxicité d'un traitement néoadjuvant combinant afatinib, trastuzumab et une chimiothérapie à base de paclitaxel, épirubicine et cyclophosphamide
Background: Dual anti-HER2 blockade with trastuzumab/pertuzumab or trastuzumab/lapatinib in combination with anthracycline/taxane-based chemotherapy can reach pCR rates of up to 60% in HER2-positive breast cancer. The DAFNE phase II study (NCT015591477) investigated a dual blockade with the irreversible pan-HER inhibitor afatinib and trastuzumab in this setting. Methods: Participants with untreated, centrally HER2-positive breast cancer were treated for 6 weeks with afatinib (20mg/day) and trastuzumab ((8)6mg/kg/3weeks) alone; followed by 12 weeks treatment with paclitaxel (80mg/m²/1week), trastuzumab and afatinib; followed by 12 weeks with epirubicin (90mg/m²/3weeks), cyclophosphamide (600mg/m²/3weeks), 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% CI: 38.5; 60.1) in 65 treated patients. Patients with hormone-receptor-negative (N=19) or -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<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 non-hematological grade 3-4 toxicities were diarrhea (7.7%), increased creatinine (4.6%), and infection (4.6%). One patient developed symptomatic congestive heart failure. Conclusion: Neoadjuvant treatment with afatinib, trastuzumab and chemotherapy showed acceptable tolerability and a pCR rate comparable to that of other anti-HER2 doublets but below challenging expectations.