scholarly journals 96O 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

2020 ◽  
Vol 31 ◽  
pp. S48 ◽  
Author(s):  
S. Loibl ◽  
C-S. Huang ◽  
M.S. Mano ◽  
T.P. Mamounas ◽  
C.E. Geyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Subgroup Analysis ◽  
Invasive Disease ◽  
Trastuzumab Emtansine ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
Breast Cancer Subgroup

The role of ado-trastuzumab emtansine in current clinical practice

2020 ◽  
pp. 107815522095186
Author(s):  
Alla Turshudzhyan
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Early Breast Cancer ◽  
Bystander Effect ◽  
Residual Disease ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Post Surgery ◽  
Her2 Breast Cancer ◽  
Randomized Controlled Studies

Objective This review reflects the literature from 2019 to 2020 on ado-trastuzumab emtansine’s (T-DM1) therapeutic use, clinical controversies, and newest perspectives on use. Data sources: PubMed was used as a database. Search “ado-trastuzumab emtansine” on June 11th, 2020 resulted in 57 publications: 20 clinical trials, two metanalysis, six randomized controlled studies, 13 reviews, and two systematic reviews. Of the 57 publications, 34 were descriptive of the topic in question and were used for this review. Data summary: T-DM1 is now used for patients with HER2 breast cancer who have residual disease post surgery after neoadjuvant chemotherapy (KATHERINE trial). Initial success prompted KRISTINE trial, which investigated whether T-DM1 can be used as a neoadjuvant therapy. While it did have fewer adverse events, T-DM1 was inferior to chemotherapy in treating early breast cancer. Noted shortcomings of the drug were toxicity limited Cmax, slow rate of internalization, lack of payload bystander effects, and number of resistance mechanisms. Proposed solutions were pre-treatment with metformin to augment drug internalization by the cell, use of second generation anti-HER2 antibody-drug conjugates to overcome developing resistance, payload swapping to increase bystander effect. Conclusions While T-DM1 has fewer side-effects, it is inferior to chemotherapy in early breast cancer treatment. More research should be done to overcome resistance pathways, identify rate-limiting intracellular processing pathways, improve bystander, and enhance internalization of the drug. Until more research is done, T-DM1 will continue to be used in HER2 positive breast cancer as well as a few other HER2 expressing tumors that fail to respond to neoadjuvant therapy.

Patient-reported outcomes (PROs) from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients (pts) with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 513-513 ◽  
Author(s):  
Andreas Schneeweiss ◽  
Sibylle Loibl ◽  
Eleftherios P. Mamounas ◽  
Gunter von Minckwitz ◽  
Max S. Mano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Phase Iii ◽  
Life Questionnaire ◽  
Meaningful Change ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Patient Reported

513 Background: The phase 3 KATHERINE (NCT01772472) study, met its primary endpoint by demonstrating significantly improved invasive disease-free survival with adjuvant T-DM1 compared to H in pts with residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy. PROs are reported here. Methods: Eligible pts had HER2-positive early breast cancer, received taxane- and H-containing neoadjuvant therapy (with/without anthracyclines) followed by surgery, and had residual invasive disease in the breast and/or axillary nodes. Pts were randomized to 14 cycles of adjuvant T-DM1 (3.6 mg/kg IV q3w) or H (6 mg/kg IV q3w) and adjuvant endocrine and radiation therapy per standard of care. The EORTC Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Breast Cancer (QLQ-BR23) were completed at screening, at day 1 of cycles 5 and 11, within 30 days after study drug completion, and at 6 and 12 months’ follow-up. Results: Of 1,486 pts randomized (T-DM1, n = 743; H, n = 743), 612 (82%) and 640 (86%), respectively, had valid baseline and ≥1 post-baseline PRO assessments. During the study, pts in both arms had similar mean scores on the QLQ-C30 and QLQ-BR23 function and symptom scales. There was no clinically meaningful change (≥10 points) from baseline in the mean scores in either arm, including on symptoms similar to AEs seen with T-DM1 (eg, fatigue). While more pts in the T-DM1 arm reported clinically meaningful deterioration in role functioning (49% vs 41%), appetite loss (38% vs 28%), constipation (47% vs 38%), fatigue (66% vs 61%), nausea/vomiting (39% vs. 30%), and systemic therapy side effects (49% vs 36%) at ≥1 assessment, the proportion reporting clinically meaningful change in functioning was similar between arms at any given assessment. Conclusions: Mean scores showed only small deterioration from baseline in patient-reported treatment-related symptoms in both study arms. While more pts in the T-DM1 arm reported deterioration at some point in several symptoms, baseline global health status and functioning were generally maintained in both arms over the treatment course. Clinical trial information: NCT01772472.

Risk of recurrence in patients with HER2+ breast cancer who achieved a pathological complete response (pCR) after neoadjuvant pertuzumab and trastuzumab (nPT), and received adjuvant trastuzumab (aT): Real-world evidence.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12648-e12648
Author(s):  
Nicholas J. Robert ◽  
Joyce O'Shaughnessy ◽  
Srinivas Annavarapu ◽  
Jie Zhou ◽  
Jesse Sussell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
Disease Free Survival ◽  
Clinical Trial Data ◽  
Complete Response ◽  
Disease Recurrence ◽  
Invasive Disease ◽  
Receptor Expression ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer

e12648 Background: The real-world risk of disease recurrence in patients with HER2+ early breast cancer who achieved pCR after receipt of nPT-based regimens and aT is unclear. Methods: Women with HER2+ breast cancer who achieved pCR after nPT-based regimens and received aT were identified in the US Oncology Network (USON). Patients initiated nPT between 2013 –2015 and were followed until recurrence of invasive disease or censoring. Data was sourced from structured fields and review of USON patient charts. Recurrence of invasive disease was defined as any of: recurrence of ipsilateral locoregional invasive breast cancer, contralateral breast cancer, distant disease recurrence, or death. Descriptive analyses were used to assess baseline demographic and clinical characteristics and the Kaplan-Meier method was used to assess invasive disease-free survival (iDFS), with stratification by nodal status. Results: A total of 238 pCR patients’ charts were reviewed. Median patient age was 52 (range: 23-88) years and a majority were White (77%). Most patients had stage IIA (39%) or IIB (24%) disease at diagnosis, ECOG score < 1 (85%), and tumor size > 2 cm (68%). At diagnosis, the majority of patients (57%) were node positive (N+) and negative for estrogen or progesterone receptor expression (51%). Median durations of therapy for nPT and aT were 4 (range: 1-8) and 7 (range: 0.03-53) months, respectively. The median duration of follow up was 47 (range: 1-70) months. Four-year iDFS probabilities are shown in the Table. Conclusions: Consistent with previously reported clinical trial data and several pooled analyses, results from this real-world study indicate that despite achieving pCR after nPT-based regimens, patients with HER2+ BC remain at risk for disease recurrence; in addition, node+ status appears to increase that risk. Therefore, patients should receive standard pertuzumab, trastuzumab adjuvant therapy to optimize treatment outcomes. [Table: see text]

scholarly journals Economic evaluation of adjuvant trastuzumab emtansine in patients with HER2-positive early breast cancer and residual invasive disease after neoadjuvant taxane and trastuzumab–based treatment in Canada

2020 ◽  
Vol 27 (6) ◽  
Author(s):  
T. Younis ◽  
A. Lee ◽  
M.E. Coombes ◽  
N. Bouganim ◽  
D. Becker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Incremental Cost ◽  
Systemic Treatment ◽  
Invasive Disease ◽  
Cost Utility ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Health States ◽  
Adjuvant Trastuzumab

Background In the katherine trial, adjuvant trastuzumab emtansine [T-DM1, Kadcyla (Genentech, South San Francisco, CA, U.S.A.)], compared with trastuzumab, significantly reduced the risk of recurrence or death by 50% (unstratified hazard ratio: 0.50; 95% confidence interval: 0.39 to 0.64; p < 0.0001) in patients with her2-positive early breast cancer (ebc) and residual invasive disease after neoadjuvant systemic treatment. A cost–utility evaluation, with probabilistic analyses, was conducted to examine the incremental cost per quality-adjusted life–year (qaly) gained associated with T-DM1 relative to trastuzumab, given the higher per-cycle cost of T-DM1. Methods A Markov model comprising a number of health states was used to examine clinical and economic out­comes over a lifetime horizon from the Canadian public payer perspective. Patients entered the model in the invasive disease-free survival (idfs) state, where they received either T-DM1 or trastuzumab. Transition probabilities between the health states were derived from the katherine trial, Canadian life tables, and published literature from other relevant clinical trials (emilia, cleopatra, and M77001). Resource use, costs, and utilities were derived from katherine, other clinical trials, published literature, provincial fee schedules, and clinical expert opinion. Sensitivity analyses were conducted for key assumptions and model parameters. Results Compared with trastuzumab, adjuvant T-DM1 was associated with a cost savings of $8,300 per patient and a 2.16 incremental qaly gain; thus T-DM1 dominated trastuzumab. Scenario analyses yielded similar results, with T-DM1 dominating trastuzumab or producing highly favourable incremental cost–utility ratios of less than $10,000 per qaly. Conclusions Adjuvant T-DM1 monotherapy is a cost-effective strategy compared with trastuzumab alone in the treatment of patients with her2-positive ebc and residual invasive disease after neoadjuvant systemic treatment.

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