Significance of baseline neutrophil-to-lymphocyte ratio for progression-free survival of patients with HER2-positive breast cancer treated with trastuzumab emtansine

Background: Lapatinib alone or in combination with other agents, mostly capecitabine is used for patients with advanced/metastatic HER2 positive breast cancer (HER2+BC) after progression on trastuzumab based therapy. Here we report our experience with lapatinib based therapy in this setting. Material and Methods: 67 consecutive patients received lapatinib based therapy. 58 (86.6%) received lapatinib + capecitabine (LC), 7 (10.4%) with other agents and 2 (3.0%) as single agent lapatinib. Data was collected from patients’ records retrospectively. Results: Objective response to lapatinib based therapy in 64 evaluable patients was 64.0% in all patients and 64.0% in patients who received LC. Median progression free survival and overall survival were 10 and 27 months in all patients and 10 and 17 months in patients who received LC, respectively. 16 (24.0%) patients had dose delay > 1 week and/or dose reduction. Conclusion: Lapatinib based therapy is an effective treatment for women with advanced/metastatic HER2+BC after prior exposure to trastuzumab. It yields meaningful response rates, progression free and overall survival. Some patients require dose adjustments.

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A neutrophil to lymphocyte ratio is predictive of response to neoadjuvant HER2-targeted therapies in the patients with HER2-positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.587 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 587-587

Author(s):

Soong June Bae ◽

Chang-Ik Yoon ◽

So Eun Park ◽

Chi Hwan Cha ◽

Dooreh Kim ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Neoadjuvant Treatment ◽

Neutrophil To Lymphocyte Ratio ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Lymphocyte Ratio ◽

Her2 Positive Breast Cancer ◽

Group A ◽

Positive Breast Cancer

587 Background: The neutrophil to lymphocyte ratio (NLR) has been reported that is associated with response to treatment and prognosis in breast cancer, but its role is unclear in HER2 positive breast cancer. In this study, the relevance of NLR for treatment efficacy was analyzed in HER2 positive breast cancer patients underwent neoadjuvant therapy. Methods: Pre-treatment NLR was assessed in 546 HER2 positive breast cancer patients divided into three groups according to neoadjuvant treatment regimens: i) chemotherapy alone, ii) chemotherapy plus trastuzumab, and iii) chemotherapy plus trastuzumab and pertuzumab. The cutoff value of NLR was defined as 2.75. We evaluated the correlation of NLR with pathologic complete response (pCR) rate to neoadjuvant treatment regimen. Results: Of all patients, 422 (77.3%) patients were classified as low NLR group (NLR < 2.75) and 124 (22.7%) patients as high NLR group (NLR≥2.75). In the low NLR group, a pCR was achieved in 59 (25.7%) of 230 patients with chemotherapy alone, 69 (57.5%) of 120 patients with chemotherapy plus trastuzumab, and 47 (65.3%) of 72 patients with chemotherapy plus trastuzumab and pertuzumab ( P< 0.001). In the high NLR group, a pCR was achieved 13 (18.8%) of 69 patients with chemotherapy alone, 5 (20.0%) of 25 patients with chemotherapy plus trastuzumab, and 18 (60.0%) of 30 patients with chemotherapy plus trastuzumab and pertuzumab in the high NLR group ( P< 0.001). The pCR rate of chemotherapy plus trastuzumab and chemotherapy plus trastuzumab and pertuzumab was similar, but higher than chemotherapy alone in patients with low NLR. However, only chemotherapy plus trastuzumab and pertuzumab showed high pCR rate compared to chemotherapy alone and chemotherapy plus trastuzumab in patients with high NLR, regardless of hormone receptor status. The elevated NLR was an independent predictor of low pCR rate in patients with chemotherapy plus trastuzumab (OR 0.18, 95% CI, 0.07 to 0.52; P= 0.002), but not in those with chemotherapy alone (OR 0.67; 95% CI, 0.34 to 1.32; P= 0.248; Pinteraction= 0.041) and chemotherapy plus trastuzumab and pertuzumab (OR 0.80; 95% CI, 0.33 to 1.92; P= 0.614; Pinteraction= 0.031). Conclusions: This study identified a possibility of NLR as an easily accessible predictive marker to guide neoadjuvant HER2 target therapy in HER2 positive early breast cancer. Further study with other cohort is needed for validation.

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Real-world study of the treatments following trastuzumab-emtansine for HER2-positive metastatic breast cancer: A multicentral cohort study (WJOG12519B).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13019 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13019-e13019

Author(s):

Sasagu Kurozumi ◽

Takamichi Yokoe ◽

Kazuki Nozawa ◽

Yukinori Ozaki ◽

Tetsuyo Maeda ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Real World ◽

Objective Response ◽

Metastatic Breast ◽

Progression Free Survival ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

e13019 Background: Since trastuzumab emtansine (T-DM1) was established as a standard treatment option, the treatment strategy of metastatic HER2-positive breast cancer has markedly changed. However, clinical evidence regarding the treatments beyond T-DM1 is insufficient. In this study, we attempted to describe real-world selection and efficacy of treatments following T-DM1 for metastatic HER2-positive breast cancer. Methods: This multi-center retrospective cohort study was conducted in 17 hospitals in Japan. Consecutive patients with metastatic HER2-positive breast cancer who had received T-DM1 and started post-T-DM1 treatments between January 2014 and December 2018 were enrolled. Patients treated with investigational drugs were excluded. The primary endpoint was objective response rate (ORR) of post-T-DM1 treatments. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results: In this study, 325 patients were eligible, of which 182 (56.0%) cases were estrogen receptor-positive and 61 (18.8%) had brain metastases. T-DM1 had been used as the first to 11th (median third) line treatment for metastatic disease. The types of post-T-DM1 treatment were as follows: 1) chemotherapy concomitant with trastuzumab and pertuzumab (n = 102; 31.4%), 2) chemotherapy concomitant with trastuzumab only (n = 78; 24.0%), 3) lapatinib with capecitabine (n = 63; 19.4%), and 4) others (n = 82; 25.2%). ORR of post-T-DM1 treatments was 22.8% (95% confidence interval [CI]: 18.1 to 28.0) and DCR was 66.6% (95% CI: 60.8 to 72.0), calculated with 290 eligible cases with the target lesion. Median PFS was 6.1 months (95%CI: 5.3 to 6.7), median TTF was 5.1 months (95%CI: 4.4 to 5.6), and median OS was 23.7 months (95%CI: 20.7 to 27.4). Conclusions: This real-world study showed that post-T-DM1 treatments had modest anti-tumor activity. Development of more effective treatments beyond T-DM1 is needed for metastatic HER2-positive breast cancer. Clinical trial information: UMIN000037747 .

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Trastuzumab emtansine (T-DM1) versus trastuzumab in Chinese patients with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy for HER2-positive breast cancer in the phase 3 KATHERINE study

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06166-y ◽

2021 ◽

Author(s):

Chiun-Sheng Huang ◽

Youngsen Yang ◽

Ava Kwong ◽

Shin-Cheh Chen ◽

Ling-Ming Tseng ◽

...

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Neoadjuvant Chemotherapy ◽

Invasive Disease ◽

Chinese Patients ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Phase 3 ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

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Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)

BMC Cancer ◽

10.1186/s12885-021-08504-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Takahiro Nakayama ◽

Tetsuhiro Yoshinami ◽

Hiroyuki Yasojima ◽

Nobuyoshi Kittaka ◽

Masato Takahashi ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Observational Study ◽

Real World ◽

Metastatic Breast ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

The Real ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Abstract Background Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. Methods In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. Results Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. Conclusions In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. Trial registration UMIN000038296; registered on 15 October 2019.

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Association of a common genetic variant of the IGF-1 gene with event-free survival in patients with HER2-positive breast cancer

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-012-1355-3 ◽

2012 ◽

Vol 139 (3) ◽

pp. 491-498 ◽

Cited By ~ 12

Author(s):

Axel Muendlein ◽

Alois H. Lang ◽

Simone Geller-Rhomberg ◽

Thomas Winder ◽

Klaus Gasser ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Variant ◽

Event Free Survival ◽

Common Genetic Variant ◽

Her2 Positive ◽

Free Survival ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

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Role of Post-Neoadjuvant therapy with trastuzumab emtansine in HER2-positive breast cancer

Medical Council ◽

10.21518/2079-701x-2021-20-68-74 ◽

2021 ◽

pp. 68-74

Author(s):

E. V. Lubennikova ◽

Ya. V. Vishnevskaya

Keyword(s):

Breast Cancer ◽

Adjuvant Therapy ◽

Neoadjuvant Therapy ◽

Locally Advanced ◽

Residual Tumor ◽

Long Term Results ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

The widespread introduction of anti-HER2 agents has changed the natural course of Her2-positive breast cancer. The use of trastuzumab, and later dual anti-HER2 blockade with pertuzumab, in neoadjuvant regimens significantly increased the chances of complete cure. However, among patients with early and locally advanced forms of Her2-positive cancer, there is a cohort with an extremely unfavorable prognosis – tumors that have not achieved complete pathomorphological regression after neoadjuvant chemotherapy.The presence of a residual tumor in Her2-positive breast cancer has long been only a prognostically unfavorable factor without the potential to influence disease outcome. The results of the international phase III study KATHERINE, which demonstrated the high efficacy of post-adjuvant therapy with trastuzumab emtansine (T-DM1) in this patient cohort, have established a new standard of care. Due to T-DM1 adjuvant therapy, the possibility to significantly improve long-term results determined the predictive characteristics of the morphological response to the choice of treatment tactics, which became an important argument in favor of neoadjuvant therapy in patients with not only locally advanced but also primarily resectable Her2-positive breast cancer, followed by personalization of therapy.This article presents our own experience with post-neoadjuvant therapy with trastuzumab emtansine in a young patient with a residual tumor. The data of the main studies in early Her2-positive breast cancer are summarized.

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CLINICAL CASE OF SUCCESFUL APPLICATION OF KADSYLA APPLICATION IN METASTATIC HER2 POSITIVE BREAST CANCER

Medical Council ◽

10.21518/2079-701x-2017-14-56-58 ◽

2017 ◽

pp. 56-58

Author(s):

D. D. Sakaeva

Keyword(s):

Breast Cancer ◽

Targeted Therapy ◽

Clinical Case ◽

Complete Response ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Pet Ct ◽

Positive Breast Cancer

A clinical case of trastuzumab emtansine in therapy line 4 in patient with metastatic HER2positive breast cancer is provided. After 10 courses of targeted therapy by the drug a complete response to the therapy was obtained. By results of PET CT conducted in the period from December 2015 to September 2017 the complete response is preserved.

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