Abstract
Abstract
Background: Panitumumab is an antibody targeting the epidermal growth factor receptor (EGFR) for which an important role has been suggested in TNBC. Consequently, we evaluated a combination of the standard chemotherapy (FEC 100 followed by docetaxel) with panitumumab as neoadjuvant therapy of operable TNBC. Complete pathologic response (pCR) was the primary endpoint, with clinical response, toxicity, and outcome as secondary endpoints. An investigation of biomarkers possibly predictive of pCR accompanied this trial. Here we focus on tumor recurrence, after a median follow up of 33 months [25-40] as on April, 1, 2013.
Methods: Sixty patients (pts) with stage II-IIIA TNBC were prospectively included. Systemic neoadjuvant treatment (ST) consisted of the anti-EGFR antibody panitumumab combined with FEC 100, followed by 4 cycles of docetaxel. All pts underwent surgery after ST completion. Patient characteristics: median tumor size: 40 mm [20-120]; SBR grade III: 71.7%; pCR rate: 55.3% and 46.8% (the Sataloff and the Chevallier classifications, respectively). Paraffin-embedded and frozen tumor samples were collected before and after ST for biomarker analysis. EGFR, IGF-1R, MET, cytokeratins 5/6 and 8/18, PTEN, P-cadherin, ALDH1, Ki-67, p53, tumoral FOXP3 expression and the number of FOXP3+ or CD8+ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry.
Results :.We have observed 9 recurrences: 1 local and 8 distant recidives, including 1 both local and distant.
The distant recidives (metastases) were as follows: brain (4 pts); brain and lungs (1 pt); lungs only (1 pt), pleura (1 pt); liver (1 pt). 6 out of the 8 metastatic pts died and all were non-pCR post-ST. The 2 alive pts had brain metastases, but reached a pCR after the ST.
Among the 9 relapsed pts 6 were 55 years old or less at the diagnosis. Seven out of those 9 pts had tumors with the clinical size equal or higher than 4 cm.
As previously reported (SABCS 2012, abstract 1081), the pCR-predictive biomarkers in this study were high CD8+ TIL count (p = 3.4.10−6) and high ratio between the CD8+ and FOXP3+ TIL counts (CD8+/FOXP3+ > 1.23, p = 8.5.10−5). With this in mind, we have evaluated whether those parameters, assessed before or after the ST, could predict the recurrences. No difference was found in the preoperative CD8+ and the FOXP3+ TIL counts, as well as in the CD8+/FOXP3+ ratio, between the patiens who have recurred and the others.
Conclusion : As it has been reported in previous studies, in our cohort of TNBC pts, the relapses occurred early after the administration of the last systemic treatment. The patients who relapsed died rapidly and most of them have not reached pCR after the ST. In addition, half of the metastatic pts got brain deposits. This implies that research on the resistance factors in TNBC should focus on those important for seeding of the “sanctuaries”, like brain. This research is ongoing in our group.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-19.