Re-Challenging Taxanes in Recurrent Breast Cancer in Patients Treated with (Neo-)Adjuvant Taxane-Based Therapy

Background: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As both drugs are used today in adjuvant regimens, efficacy data from pivotal trials in the metastatic setting in taxanenaive populations cannot reliably be used as references. Patients and Methods: The Taxane Re-Challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data on their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first- or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed a response rate of 48.6% (including complete responses in 27.0%). The response rate was dependent on the disease-free interval ( 2 years: 63.3%; p = 0.04) and visceral metastasis (present: 62.5%; not present 32.4%; p = 0.01). Patients without visceral metastasis and with a disease-free interval of > 2 years achieved the longest overall survival. Hormone and HER2 receptor status were not predictive; however, triple-negative tumors responded in 50.0%. The overall response rate of later-line taxane-based treatment was 28.2%. Conclusion: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.Hintergrund: Docetaxel und Paclitaxel gehören zu den aktivsten Substanzen in der Behandlung des Mammakarzinoms. Da sie heute häufig bereits zur adjuvanten Behandlung eingesetzt werden, können Effektivitätsdaten von früheren Studien mit Taxan-naiven, metastasierten Patientinnen nicht mehr als zuverlässig angesehen werden. Patienten und Methoden: Für die Taxane Re-Challenge Kohortenstudie haben wir Teilnehmerinnen 6 prospektiver Taxanbasierter (neo-)adjuvanter Studien mit rezidivierter Erkrankung identifiziert und Daten zur weiteren Behandlung gesammelt. Bei 106 (27,8%) von 381 Patientinnen mit einem Rezidiv oder einer Metastase wurde erneut ein Taxan in der ersten oder späteren Behandlung eingesetzt. Ergebnisse: Taxane wurden in der Erstlinie bei 74 Patientinnen angewandt und zeigten eine Ansprechrate von 48,6% (inklusive Komplettremissionen in 27,0%). Die Ansprechrate war vom krankheitsfreien Intervall ( 2 Jahre: 63,3%; p = 0,04) und dem Vorhandensein viszeraler Metastasen (vorhanden: 62,5%; nicht vorhanden: 32,4%; p = 0,01) abhängig. Patientinnen ohne viszerale Metastasen und mit einem krankheitsfreien Intervall > 2 Jahre überlebten am längsten. Hormon- und HER2-Rezeptorstatus waren für das Ansprechen nicht prädiktiv, jedoch sprachen tripelnegative Tumoren in 50.0% auf die erneute Taxan-Therapie an. Die Gesamtansprechrate auf ein erneutes Taxan in der späteren Linie betrug 28.2%. Schlussfolgerung: Der Wiedereinsatz von Taxanen erscheint effektiv und steht somit als sinnvolle Option für mit Taxanen (neo-)adjuvant vorbehandelte Patientinnen zur Verfügung

Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer : a substudy of the neoadjuvant GeparQuinto trial

Introduction: We have recently described an increased lymphocytic infiltration rate in breast carcinoma tissue is a significant response predictor for anthracycline/taxane-based neoadjuvant chemotherapy (NACT). The aim of this study was to prospectively validate the tumor-associated lymphocyte infiltrate as predictive marker for response to anthracycline/taxane-based NACT. Patients and Methods: The immunological infiltrate was prospectively evaluated in a total of 313 core biopsies from HER2 negative patients of the multicenter PREDICT study, a substudy of the neoadjuvant GeparQuinto study. Intratumoral lymphocytes (iTuLy), stromal lymphocytes (strLy) as well as lymphocyte-predominant breast cancer (LPBC) were evaluated by histopathological assessment. Pathological complete response (pCR) rates were analyzed and compared between the defined subgroups using the exact test of Fisher. Results: Patients with lymphocyte-predominant breast cancer (LPBC) had a significantly increased pCR rate of 36.6%, compared to non-LPBC patients (14.3%, p<0.001). LPBC and stromal lymphocytes were significantly independent predictors for pCR in multivariate analysis (LPBC: OR 2.7, p = 0.003, strLy: OR 1.2, p = 0.01). The amount of intratumoral lymphocytes was significantly predictive for pCR in univariate (OR 1.2, p = 0.01) but not in multivariate logistic regression analysis (OR 1.2, p = 0.11). Conclusion: Confirming previous investigations of our group, we have prospectively validated in an independent cohort that an increased immunological infiltrate in breast tumor tissue is predictive for response to anthracycline/taxane-based NACT. Patients with LPBC and increased stromal lymphocyte infiltration have significantly increased pCR rates. The lymphocytic infiltrate is a promising additional parameter for histopathological evaluation of breast cancer core biopsies

Univariate and multivariate analysis.

*<p>p-value: logistic regression analysis.</p

CONSORT statement and workflow of the PREDICT study.

<p>EC-T, epirubicin/cyclophosphamid followed by docetaxel; Pts, patients; pCR, pathologic complete response.</p