Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane based chemotherapy in operable triple negative breast cancer: Identification of biologically-defined signatures predicting treatment impact
Mené sur 60 patientes atteintes d'un cancer du sein triplement négatif opérable, cet essai de phase II évalue l'efficacité, du point de vue de la réponse pathologique complète, et la toxicité du panitumumab en combinaison avec une chimiothérapie à base d'anthracycline et de taxane pour un traitement néoadjuvant, puis identifie divers biomarqueurs associés à la réponse thérapeutique
Background : Triple negative breast cancer (TNBC) is a heterogeneous group of tumors for some of which the Epithelial Growth Factor Receptor (EGFR) pathway may play an important role. We investigated the efficacy and toxicity of an anti-EGFR antibody (panitumumab) combined with a standard neoadjuvant anthracycline-taxane based chemotherapy in patients with operable, stage II-III, TNBC. Methods : Treatment in this multicentric neoadjuvant pilot study consisted of panitumumab (9 mg/kg) for 8 cycles q.3 weeks combined with 4 cycles of 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC100: 500/100/500 mg/m2) q.3 weeks followed by 4 cycles of docetaxel (T: 100 mg/m2) q.3 weeks. Following therapy, all patients underwent surgical resection. Pathological complete response (pCR) in evaluable patients was the main endpoint while clinical response, toxicity and ancillary studies were secondary endpoints. Paraffin-embedded and frozen tumor samples were systematically collected with the aim to identify predictive biomarkers of efficacy and resistance in order to select biologically defined subpopulations for potential further clinical development of the anti-EGFR antibody. Results : Sixty patients were enrolled with 47 assessable for pathologic response. The pathological complete response (pCR) rates were 46.8% [95% CI: 32.5-61.1] and 55.3% [95% CI: 41.1-69.5] according respectively to Chevallier and Sataloff classifications. The complete clinical response rate (cCR) was 37.5%. Conservative surgery was performed in 87% of cases. Toxicity was manageable. The association of high EGFR and low cytokeratin 8/18 expression in tumor cells on one hand and high density of CD8+ tumor-infiltrating lymphocytes on the other hand were significantly predictive of pCR. Conclusions : Panitumumab in combination with FEC100 followed by docetaxel appears efficacious, with acceptable toxicity, as neoadjuvant therapy of operable TNBC. Several biomarkers could help define large subsets of patients with high probability of pCR, suggesting a potential interest to further develop this combination in biologically defined subgroups of patients with TNBC.
Annals of Oncology 2014