Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

Park, Yeon Hee; Luk, Mai‐Yee; Soong, I.; Yuen, Tony Y.S.; Ng, TY; Mo, Frankie; Chan, KL; Wong, Sik-Nin; Tsang, Janice; Leung, Carmen; Suen, Joyce; Ngan, Roger K.C.

doi:10.12809/hkmj176808

Cited by 5 publications

(4 citation statements)

References 17 publications

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“…The T-DM1 benefit-risk profile in ELAINA is consistent with previous clinical trials ( 18 , 19 , 35 , 36 ) and real-world data in patients with pretreated LABC/mBC, including Chinese patients ( 37 - 41 ). A recent network meta-analysis suggested that pyrotinib plus capecitabine may be the most efficacious treatment among the nine regimens (including T-DM1) evaluated for patients with previously treated HER2-positive mBC ( 42 ).…”

Section: Discussionsupporting

confidence: 86%

Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansine vs. lapatinib plus capecitabine in Chinese patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy

Wang¹,

Li²,

Yin³

et al. 2023

Transl Breast Cancer Res

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Background: The antibody-drug conjugate (ADCs) trastuzumab emtansine (T-DM1) is approved for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab and a taxane. The phase III ELAINA trial aimed to determine the clinical utility of T-DM1 in Chinese patients. Methods: ELAINA was a randomized, multicenter, open-label bridging study of Chinese patients with HER2-positive locally advanced breast cancer (LABC) or mBC previously treated with trastuzumab and a taxane. Using an interactive voice/internet response system, patients were randomized 3:1 to receive T-DM1 or lapatinib plus capecitabine. Patents were stratified by number of prior therapies in this diseasesetting and by presence of visceral disease using a permuted block randomization scheme. Patients received treatment until disease progression, unmanageable toxicity, or study termination. After that, data on survival and subsequent cancer therapies were collected at approximately 3-month intervals. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints were overall response rate, duration of response, overall survival (OS), safety, patient-reported quality of life, and pharmacokinetics (PKs). Results: ELAINA was fully enrolled with 200 patients randomized to T-DM1 (n=151) or lapatinib plus capecitabine (n=49). Median treatment duration was approximately 6 months in each study arm. Median follow-up time was approximately 9 months for all analyses except for OS. T-DM1 was associated with a 15% reduction in risk of disease progression or death compared with lapatinib plus capecitabine [stratified ^ ORCID: 0000-0002-4295-0173.

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Section: Discussionsupporting

confidence: 86%

Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansine vs. lapatinib plus capecitabine in Chinese patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy

Wang¹,

Li²,

Yin³

et al. 2023

Transl Breast Cancer Res

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“…Furthermore, thrombocytopenia that developed in the first four T-DM1 cycles was predictive of a longer TTD in T-DM1 treatment. Thrombocytopenia has been identified as a characteristic of T-DM1 and as the most common grade ≥3 and dose-limiting adverse event in both clinical trials (10)(11)(12) and real-life studies (17,24,25). To the best of our knowledge, only two reports in the literature have studied the predictive value of thrombocytopenia during T-DM1 treatment.…”

Section: Discussionmentioning

confidence: 99%

Early thrombocytopenia predicts longer time‑to‑treatment discontinuation in trastuzumab emtansine treatment

Sahin,

Caner,

Ocak

et al. 2023

Oncol Lett

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Thrombocytopenia is a characteristic adverse event of trastuzumab emtansine (T-DM1), one of the essential treatment options for human epithelial growth factor receptor 2 (HER2)-positive breast cancer. The present study investigated the predictive value of thrombocytopenia for time-to-treatment discontinuation (TTD) in patients receiving T-DM1 for advanced-stage HER2-positive breast cancer. The present observational study enrolled 138 patients who received T-DM1 at six oncology centers from January 2016 to December 2021. Univariate and multivariate Cox regression analyses were performed to determine the factors affecting TTD. The median age of patients was 50 years (range, 26-83).The median number of T-DM1 cycles was 9 (range, 2-58), the overall response rate was 50.0% and the disease control rate was 69.6%. At a median follow-up time of 19.3 months, the median TTD was 9.5 months [95% confidence interval (CI), 7.3-11.7], and the median overall survival was 28.2 months (95% CI, 19.2-37.2). Thrombocytopenia during treatment was observed in 39% of all patients, and 66.7% of these patients experienced early thrombocytopenia (in the first four treatment cycles). Multivariate analysis revealed that the independent factors for TTD were hormone receptor status [hazard ratio (HR), 1.837; 95% CI, 1.249-2.701; P= 0.002], Eastern Cooperative Oncology Group performance status score (HR, 3.269; 95% CI, 1.788-5.976; P<0.001) and thrombocytopenia during treatment (HR, 0.297; 95% CI, 0.198-0.446; P<0.001). Patients with early thrombocytopenia had a significantly longer TTD of 17.3 months (95% CI, 11.8-22.8) compared with 7.6 months (95% CI, 5.8-9.4) for patients without early thrombocytopenia (P<0.001). The results of the present study indicated that patients with early thrombocytopenia had improved survival outcomes compared with those without. Thus, maximum benefit from T-DM1 treatment may be achieved by confirming the predictive role of thrombocytopenia in T-DM1 treatment in prospective studies and large-scale cohorts.

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“…Limited data exist on T-DM1 effectiveness outside clinical trials. In a single-center retrospective study in Spain ( n = 15) and a five-center retrospective study in Hong Kong ( n = 37), median PFS was 10 and 6 months, respectively, and median OS was 34 months and not reached, respectively [ 10 , 11 ]. A retrospective observational multicenter study in Italy evaluated 250 patients treated with T-DM1, including those with pertuzumab pretreatment [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Retrospective Observational Study of Outcomes in HER2-Positive Metastatic Breast Cancer (mBC) Patients Treated with Ado-Trastuzumab Emtansine (T-DM1) and Subsequent Treatments After T-DM1 in the United States

Denduluri

Espirito

Hackshaw

et al. 2022

Drugs - Real World Outcomes

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Background Limited evidence exists on real-world outcomes with ado-trastuzumab emtansine (T-DM1) treatment and the effectiveness of subsequent therapies. Objective This study evaluated treatment patterns and outcomes of patients treated with T-DM1 and post-T-DM1 therapy in the United States.Patients and methods Adult patients with HER2-positive (HER2+) metastatic breast cancer (mBC) initiating treatment with T-DM1 between 1/1/2013 and 9/30/2018 were included and followed through 12/31/2018. Data were obtained from the iKnowMed electronic health record. Demographic, clinical, and pre-and post-T-DM1 treatment characteristics were described. The Kaplan-Meier method was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). Results Of 318 patients treated with T-DM1, 184 (57.9%) had prior treatment with pertuzumab. The median age was 58 years. Most patients had visceral disease (93.4%), and 62.3% had two or more prior treatments for mBC before T-DM1 (range 0-9). The most common subsequent regimens were trastuzumab + vinorelbine (22.5%), HER2-targeted monotherapy (22.5%), and trastuzumab + other chemotherapy (19.6%). Median TTD with T-DM1 was 5.9 months (95% confidence interval [CI] 4.6-6.9); median OS from the start of T-DM1 therapy was 19.2 months (95% CI 16.8-24.5). Conclusions Patients treated with T-DM1 in this study appeared to have more advanced disease than patients in clinical trials and were treated in later lines of therapy. Variability was observed across subsequent therapy selections. Treatment patterns and outcomes appeared comparable for patients who received prior pertuzumab. The short treatment durations and survival with T-DM1 therapy in the real-world setting underscore the need for effective post-trastuzumab therapies.

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Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal growth factor receptor 2–positive breast cancer

Cited by 5 publications

References 17 publications

Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansine vs. lapatinib plus capecitabine in Chinese patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy

Primary results of ELAINA: a randomized, multicenter, open-label, phase III study of the efficacy and safety of trastuzumab emtansine vs. lapatinib plus capecitabine in Chinese patients with HER2-positive locally advanced or metastatic breast cancer who have received prior trastuzumab-based therapy

Early thrombocytopenia predicts longer time‑to‑treatment discontinuation in trastuzumab emtansine treatment

Retrospective Observational Study of Outcomes in HER2-Positive Metastatic Breast Cancer (mBC) Patients Treated with Ado-Trastuzumab Emtansine (T-DM1) and Subsequent Treatments After T-DM1 in the United States

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