Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

Abstract Background Trastuzumab emtansine (T-DM1) treatment for human epidermal growth factor receptor-2 (HER2)-positive metastatic breast cancer after taxane with trastuzumab and pertuzumab is standard therapy. However, treatment strategies beyond T-DM1 are still in development with insufficient evidence of their effectiveness. Here, we aimed to evaluate real-world treatment choice and efficacy of treatments after T-DM1 for HER2-positive metastatic breast cancer. Methods In this multi-centre retrospective cohort study involving 17 hospitals, 325 female HER2-positive metastatic breast cancer patients whose post-T-DM1 treatment began between April 15, 2014 and December 31, 2018 were enrolled. The primary end point was the objective response rate (ORR) of post-T-DM1 treatments. Secondary end points included disease control rate (DCR), progression-free survival (PFS), time to treatment failure (TTF), and overall survival (OS). Results The median number of prior treatments of post-T-DM1 treatment was four. The types of post-T-DM1 treatments included (1) chemotherapy in combination with trastuzumab and pertuzumab (n = 102; 31.4%), (2) chemotherapy concomitant with trastuzumab (n = 78; 24.0%), (3), lapatinib with capecitabine (n = 63; 19.4%), and (4) others (n = 82; 25.2%). ORR was 22.8% [95% confidence interval (CI): 18.1–28.0], DCR = 66.6% (95% CI 60.8–72.0), median PFS = 6.1 months (95% CI 5.3–6.7), median TTF = 5.1 months (95% CI 4.4–5.6), and median OS = 23.7 months (95% CI 20.7–27.4). Conclusion The benefits of treatments after T-DM1 are limited. Further investigation of new treatment strategies beyond T-DM1 is awaited for HER2-positive metastatic breast cancer patients.

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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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PCN104 Cost-Utility MODEL of Trastuzumab Emtansine (T-DM1) in HER2-Positive, Unresectable, Locally Advanced or Metastatic Breast Cancer Previously Treated with Trastuzumab and a Taxane, Compared with Capecitabine PLUS Lapatinib, Trastuzumab PLUS Capecitabine and Capecitabine ALONE in Turkey

Value in Health ◽

10.1016/j.jval.2020.08.241 ◽

2020 ◽

Vol 23 ◽

pp. S441

Author(s):

B. Akyol Ersoy ◽

E. Erdogan-Ciftci ◽

L. Yanik ◽

B. Guler ◽

G. Ozcan ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Locally Advanced ◽

Metastatic Breast ◽

Cost Utility ◽

Trastuzumab Emtansine ◽

Utility Model ◽

Her2 Positive ◽

Previously Treated

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Trastuzumab emtansine plus pertuzumab in Japanese patients with HER2-positive metastatic breast cancer: a phase Ib study

Breast Cancer ◽

10.1007/s12282-018-0887-z ◽

2018 ◽

Vol 26 (1) ◽

pp. 39-46 ◽

Cited By ~ 1

Author(s):

Emi Noguchi ◽

Kenji Tamura ◽

Masaya Hattori ◽

Jun Horiguchi ◽

Nobuaki Sato ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Japanese Patients ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Phase Ib

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Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial

Cancers ◽

10.3390/cancers12123509 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3509

Author(s):

Elena López-Miranda ◽

José Manuel Pérez-García ◽

Serena Di Cosimo ◽

Etienne Brain ◽

Maja Ravnik ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Liposomal Doxorubicin ◽

Metastatic Breast ◽

Pegylated Liposomal Doxorubicin ◽

Maximum Tolerated Dose ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

Open Label ◽

Phase Ib

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the “3 plus 3” dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3–67.7) with a median duration of response of 6.9 months (95%CI, 4.8–9.1). Clinical benefit rate was 66.7% (95%CI, 38.4–88.2) and median progression-free survival was 7.2 months (95%CI, 4.5–9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.

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