Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial
Mené sur 1 206 patientes atteintes d'un cancer du sein de stade précoce, cet essai de phase III compare, selon le statut HER2 de la tumeur, l'efficacité, du point de vue du taux de réponse complète, et la toxicité de l'ajout du pertuzumab au trastuzumab et à une chimiothérapie néoadjuvante combinant paclitaxel (ou nab-paclitaxel), épirubicine et cyclophosphamide
Background: The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n=396) in comparison to the HER2- cohort. Patients and methods: Patients with histologically confirmed breast cancer (n=1206) received 4 cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0. Results: Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% vs 22.0%, p<0.0001 ), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9%; (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxicities were significantly more common in HER2+ than in HER2- patients, with grade 3-4 diarrhea in 7.6% vs 0.9% (p<0.001) and febrile neutropenia in 6.3% vs 3.3% (p=0.023) of patients. LVEF decreases from baseline were uncommon, with 2.0% vs 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline. Conclusion: In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane-epirubicin-cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.