S3-2: Neoadjuvant Chemotherapy Adapted by Interim Response Improves Overall Survival of Primary Breast Cancer Patients – Results of the GeparTrio Trial.

Abstract

Background: The GeparTrio phase III trial investigated the concept of interim response-adapted neoadjuvant chemotherapy. Patients with an early response after 2 cycles chemotherapy were considered highly chemo-sensitive and randomized to additional 2 chemotherapy cycles compared to standard treatment. Patients with no early response were considered less chemo-sensitive and randomized to continue with a non-cross-resistant chemotherapy or with standard chemotherapy. Pathological complete response (pCR) rates were different between responders and non-responders but not between the randomized arms (von Minckwitz G, et al JNCI 2008+2008; Huober et al. BCRT 2010). We report here on the results of the secondary endpoints: disease-free (DFS) and overall survival (OS). Patients and Methods: 2072 patients with operable or locally advanced breast cancer were treated with 2 cycles TAC (docetaxel, doxorubicin cyclophosphamide) before interim response assessment. Responders were randomized to additional TACx4 (N=704) or TACx6 (N=686) and non-responders to TACx4 (N=321) or NXx4 (vinorelbine, capecitabine) (N=301). None of the HER2+ patients received Trastuzumab. Endocrine treatment was given postoperatively to ER+ and/or PgR+ patients. We observed 480 recurrences and 302 deaths during median 62 months of follow up. Results: Patients receiving the experimental treatments (TACx8 or TACx2-NXx4) showed a longer DFS (HR 0.71; 95%CI 0.60−0.86, p<0.001) and longer OS (HR 0.79; 95%CI 0.63−0.99, p=0.048) compared to patients receiving standard TACx6 treatment. Treatment effects on DFS were restricted to patients with luminal A (p=0.003), luminal B (HER2−) (p=0.006) and luminal B(HER2+) (p=0.04) tumors. Experimental treatments did not improve outcome in HER2+(non-luminal) (p=1.0) and triple-negative (p=0.5) tumors. Responders showed a significant longer DFS (HR 0.79; 95%CI 0.62−0.97), p=0.026) and a trend towards a longer OS (HR 0.76; 95%CI 0.57−1.01, p=0.061) if they were treated with TACx8 compared to TACx6. Non-responders showed a longer DFS (HR 0.6; 95%CI 0.43−0.82, p=0.001) but not OS (HR 0.85; 95%CI 0.57−1.27, p=0.4) when treated with TACx2-NXx4 compared to TACx6. Results according to phenotypes of responders and non-responders were comparable to the overall comparison. In general, patients with a pCR showed a better DFS if they had triple-negative (p<0.0001), HER2+(non-luminal) (p<0.0001) or luminal B(HER2−) (p=0.004), but not if they had luminal A (p=0.66) or luminal B (HER2+) (0.67) disease. Conclusion: Adapting neoadjuvant chemotherapy according to interim response leads to better DFS and OS and represents therefore a unique advantage over adjuvant treatment. The investigated strategies to improve standard chemotherapy were most effective in the luminal A and B phenotypes. These phenotypes are usually considered less chemo-sensitive and pCR is not a prognostic factor. This might explain why the observed survival advantages could not be predicted by pCR. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S3-2.

Current and future role of neoadjuvant therapy for breast cancer

“…This study showed that a response-guided (switch to another chemotherapy in case of no early response or increased cycle number in case of an early response) chemotherapy regimen is more effective compared to a non-individualized approach with a fixed number of cycles using the same chemotherapy agents [37]. Women who were treated with response-guided chemotherapy had a significantly longer DFS and OS (Fig.…”

“…2. GeparTrio study: DFS and OS after conventional (TACx6) vs. response guided (TACx8 or TAC-NX) treatment [37]. distinct settings.…”

Serial MRI scans help in assessing early response to neoadjuvant chemotherapy and tailoring breast cancer treatment

“…In addition, early identification of non-responders resulted in switching NAC and increased the chances of achieving pCR amongst the late responders compared to non-responders to both treatments (13.2% vs. 0%) [24]. The GEPARTRIO phase-III study showed improved DFS in non-responders that showed improved response after switching treatment [27].…”

Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer

“…Trastuzumab for HER2−positive cases was not available at that time. Detailed information on the studies is available in the original publications [8][9][10][11]. All patients gave written informed consent for study participation and biomaterial collection; all necessary approvals by ethics committees and authorities were obtained.…”