Residual Disease After NeoAdjuvant Therapy

CTNeoBC obtained data from 12 identified international trials and 11,955 patients were included in the responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39–0·51; ypT0/is ypN0: 0·48, 0·43–0·54) and OS (0·36, 0·30–0·44; 0·36, 0·31–0·42).

Ref: 1) Cortazar P, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72.

As summarized by Prof. Geyer, the pCR rates in patients who received dual blockade neoadjuvant therapy in NeoSphere and TRYPHAENA range from 39.3% - 63.6% with different chemo combinations. Hence ~40-60% patients may be present with residual invasive disease after neoadjuvant therapy with dual blockade.

Ref: 1) Gianni L, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol

. 2012 Jan;13(1):25-32. 2) Schneeweiss A, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol

. 2013 Sep;24(9):2278-84.

Patients were eligible for participation in the KATHERINE trial if they had histologically confirmed, HER2-positive, nonmetastatic, invasive primary breast cancer (clinical tumor stage T1 to T4, nodal stage N0 to N3, and metastasis stage M0 excluding clinical stage T1aN0 or T1bN0) at presentation and if residual invasive disease was detected pathologically in the surgical specimen of the breast or axillary lymph nodes after completion of taxane-based neoadjuvant chemotherapy administered with trastuzumab.

Ref: 1) von Minckwitz G, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628.

Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. 

The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.

In a subgroup analysis comparing adjuvant radiotherapy (ART) vs no-ART, it was reported that IDFS benefit was consistent regardless of ART. No new safety signals were observed with concomitant ART.

A subgroup analysis of invasive disease–free survival revealed a consistent benefit of T-DM1 across stratification cohorts and other subgroups, including patients with either no residual invasive primary disease or residual primary disease of 1 cm or less in the breast. In an exploratory analysis, benefit was seen in 331 patients with residual invasive disease of 1 cm or less in the breast and negative lymph nodes, with invasive-disease events in 17 patients in the T-DM1 group (10.0%) and 25 patients in the trastuzumab group (15.5%) (hazard ratio, 0.60; 95% CI, 0.33 to 1.12).

Ref: 1) von Minckwitz G, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628. 2) Loibl S, et al. Adjuvant trastuzumab emtansine (T-DM1) vs trastuzumab (T) in patients (pts) with residual invasive disease after neoadjuvant therapy for HER2+ breast cancer: Subgroup analysis from KATHERINE. Abstract 96O and oral presentation at ESMO Breast Cancer 2020 (abstract available at: https://oncologypro.esmo.org/meeting-resources/esmo-breast-cancer-virtual-meeting-2020/adjuvant-trastuzumab-emtansine-t-dm1-vs-trastuzumab-t-in-patients-pts-with-residual-invasive-disease-after-neoadjuvant-therapy-for-her2-brea)

IDFS at 3 years were 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease–free survival, the primary end point, was significantly higher among patients who received T-DM1 than among those who received trastuzumab (hazard ratio, 0.50; 95% confidence interval [CI], 0.39 to 0.64; P<0.001). i.e. T-DM1 reduced the risk of an IDFS event by 50% compared with trastuzumab.

Ref: 1) von Minckwitz G, et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med. 2019 Feb 14;380(7):617-628.