Trastuzumab emtansine...as a single agent, is indicated for the adjuvant treatment of adult patients with HER2-positive early breast cancer who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy.

Chugai Pharmaceutical...announced today that it has obtained approval for anti-HER2 antibody-tubulin polymerization inhibitor conjugate Kadcyla® Intravenous Infusion 100 mg and 160 mg [generic name: trastuzumab emtansine (genetical recombination)] from the Ministry of Health, Labour and Welfare for an additional indication of HER2-positive postoperative breast cancer.

Kadcyla, as a single agent, is indicated for the adjuvant treatment of adult patients with HER2-positive early breast cancer who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy.

KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate indicated, as a single agent, for...the treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination.

Patients with HER2-positive breast cancer with pathologic invasive residual disease at surgery after standard preoperative chemotherapy and HER2-targeted therapy should be offered 14 cycles of adjuvant T-DM1, unless there is disease recurrence or unmanageable toxicity.

For patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant ChT combined with anti-HER2 therapy, substitution of adjuvant trastuzumab with trastuzumab emtansine (T-DM1) decreases the risk of recurrence of invasive breast cancer or death by 50% and is recommended, once approved and where available.

...NCCN panel included T-DM1 as an option for treatment of patients with HER-2 positive metastatic breast cancer.

Roche...announced today positive long-term follow-up data from the pivotal, phase III KATHERINE study in people with HER2-positive early-stage breast cancer (eBC) who have residual invasive disease following neoadjuvant (before surgery) treatment. A statistically significant and clinically meaningful improvement in overall survival (OS), a secondary endpoint, was observed with adjuvant (post-surgery) Kadcyla® (trastuzumab emtansine) compared to Herceptin® (trastuzumab): at the 7-year landmark OS rates were 89.07% and 84.37% with Kadcyla and Herceptin, respectively (hazard ratio [HR]=0.66, 95% CI: (0.51, 0.87), p-value =0.0027).

Patients had HER2-positive, locally advanced, or metastatic BC progressing after chemotherapy and anti-HER2 therapy or ≤6 months after adjuvant therapy….Median (95% confidence interval) progression-free survival was 6.8 months (5.8-7.6 months) and 5.7 months (5.5-7.0 months) in cohorts 1 and 2, respectively; median overall survival was 27.2 months (25.5-28.7 months) and 29.5 months (21.1 months to non-estimable)....Cohort 2 results aligned with previous findings in Asian patients, supporting the manageable safety profile and use of T-DM1 in advanced BC.

Pooled results showed T-DM1 substantially improved overall survival (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.67–0.85; I2 = 0%) and progression-free survival (HR, 0.67; 95% CI, 0.52–0.85; I2 = 75%)....T-DM1 is effective for the treatment of patients with HER2-positive metastatic breast cancer...

At the 2nd interim analysis, with a median follow up of 19 months, median OS was 22.7 vs 34.3 months (HR, 0.43; 95% CI: 0.24–0.77) with CL vs T-DM1….T-DM1 conferred a clinically meaningful benefit compared with CL in Asian patients with HT-pretreated HER2-positive LA/MBC...

High vs low HER2 expression was associated with worse outcome (HR 2.02; 95% CI 1.32–3.11) within the H arm, but not within the T-DM1 arm (HR 1.01; 95% CI 0.56–1.83)....exploratory analyses provide the first data on the relationship between biomarker expression in residual disease after HER2-targeted therapy and outcomes....T-DM1 benefit appeared to be independent of all biomarkers assessed.

Pts had HER2-positive, locally advanced or mBC with progression after chemotherapy and anti-HER2 therapy or ≤6 months (mo) of completing adjuvant therapy. T-DM1 3.6 mg/kg was given intravenously every 3 weeks until disease progression...data confirm prior observations in an Asian subgroup of the phase 3 EMILIA trial of T-DM1 in pts with previously treated mBC. Although the G≥3 TCP rate was higher in the Asia cohort, the majority of these events resolved fully....data reinforce the favorable T-DM1 benefit-risk profile in mBC.

KATHERINE enrolled HER2-positive EBC patients...Patients were randomized to adjuvant T-DM1 (n=743) or trastuzumab (n=743) for 14 cycles….T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors…

In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3–5.6) months and 18.9 (95% CI 17.1–21.3) months...HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population.

Median progression-free survival (PFS) was 6.9 months (95% confidence interval [CI], 6.0-7.6). Median overall survival (OS) was 27.2 months (95% CI, 25.5-28.7)....thereby supporting T-DM1 as safe, tolerable and efficacious treatment for patients with previously treated HER2-positive advanced BC.

...a phase 3, open-label trial involving patients with HER2-positive early breast cancer...Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles….The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease–free survival was significantly higher in the T-DM1 group than in the trastuzumab group...

Adjuvant T-DM1 substantially improved IDFS in patients with HER2-positive early breast cancer with residual disease after completion of neoadjuvant therapy.

Tumors were evaluated for HER2 (n = 866), EGFR (n = 832), and HER3 (n = 860) mRNA expression by quantitative reverse transcriptase PCR; for PTEN protein expression (n = 271) by IHC; and for PIK3CA mutations (n = 259) using a mutation detection kit…Longer progression-free survival (PFS) and overall survival (OS) were observed with T-DM1 compared with capecitabine plus lapatinib in all biomarker subgroups.

...HER2 status must be prospectively, centrally tested and be HER2-positive based on central laboratory assay results...

The median PFS in the novel ADCs group and T-DM1 group were 7.0 months versus 4.0 months, respectively, and ORR was 54.8% versus 22.5%, CBR was 65.8% versus 47.9%, respectively. In subgroups analysis, the PFS were both significantly improved in patients receiving T-Dxd and other novel ADCs compared with T-DM1....In patients with HER2-positive MBC previously treated with TKIs, both T-Dxd and other novel anti-HER2 ADCs yielded statistically significant better PFS than T-DM1 did, with tolerable toxicities.

After weighting, median OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34-0.89]; P=0.013)….These results support the superior effectiveness and clinical relevance of T-DM1 versus LC in patients with HER2-positive BCBM in the real world.

The 5-year iDFS for T-DM1 was 97.0% (95% CI, 95.3-98.8%), the 5-year recurrence-free interval (RFI) was 98.6% (95% CI: 97.4-99.8%) and the 5-year overall survival (OS) for T-DM1 was 97.8 % (95% CI, 96.3-99.3%)....With longer follow-up, adjuvant T-DM1 confirmed outstanding long-term outcomes among patients with stage I HER2+ breast cancer, demonstrating a 5-year RFI of 98.6%.

We included data from all patients with a confirmed diagnosis of HER2+ MBC treated from 2014 to 2021... endpoints included adoption of pertuzumab-based regimen and T-DM1 in the palliative setting and their median Time to Treatment Discontinuation (TTD) in a real-world scenario....With a median follow-up of 2 years, median OS was 49 months (CI95% 44-59)….T-DM1 was accessible to 22% of the patients, mostly in 2nd (28%) or 3rd line and beyond (50%), with median TTD of 10.2 months (CI95% 9-13)....In the largest Brazilian real-world study of patients with HER2+ MBC treated in the private health system, we found similar outcomes as those reported in North-American and European cohorts, both in terms of OS and TTD with standard-of-care therapies.

This retrospective study aims to evaluate the efficacy and toxicity of T-DM1 in advanced HER2 positive female BC patients….The overall response rate was 80%, 8(10%) achieved a complete response, 36 (45%) had a partial response, and 12 (15%) patients had stable disease....Within the median follow-up period of 18 months, the median PFS was 10 months and OS was 27 months.

To investigate whether these results might be observed in the clinic, we conducted retrospective analyses on a cohort of 164 HER2 positive metastatic breast cancer patients treated at MSKCC who received T-DM1. Among these patients, 21 (12.8%) were taking statins concurrently with T-DM1, and the median progression-free survival in the patients who received statins was 14 months (95% confidence interval, 3.5-24 months) compared to 5.4 months (95% confidence interval, 3.9-7.0 months) in those who had no record of statin use (p=0.1).

This systematic review aimed to identify neoadjuvant anti-human epidermal growth factor receptor 2 (HER2) therapies with the best balance between efficacy and safety.... The T-DM1PC, T-DM1, and PTC_T-DM1P regimens had the optimal balance between efficacy and safety, while DFS was highest for the PTC regimen.

HER2-positive patients with residual breast or nodal involvement received trastuzumab-emtanzine up to one year....cCR was achieved in 8 of 10 patients in the HER2-positive group....Contemporary systemic therapy regimens provide the rate of pCR up to 60-70%.

The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy...In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC.

T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC...Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001).

The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis (P < .0001)....Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS...

We included 493 systemically treated patients consecutively diagnosed with HER2 + ABC in 2008-2017 from the SOutheast Netherlands Advanced BREast cancer (SONABRE) Registry….The median OS in 2008-2012 versus 2013-2017 was 28.3 versus 39.7 months in all patients (adjusted hazard ratio (adjHR) 0.85, 95%CI 0.66-1.08), 29.9 versus 36.3 months in patients with HR + /HER2 + disease (adjHR 0.97, 95%CI 0.72-1.32), and 22.7 versus 40.9 months in patients with HR-/HER2 + disease (adjHR 0.59, 95%CI 0.38-0.92).... The survival of patients with HER2 + ABC improved since the introduction of pertuzumab and T-DM1.

We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM.

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...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).

CONTRADICTING EVIDENCE: The results revealed a significant difference in the median PFS with the first subsequent treatment between patients with the PFS of less than and more than 3 months [5.1 (95% CI 1.7-6.2) vs 6.2 (95% CI 4.0-11.3) months, P = .03].This is the first study to evaluate the survival outcomes of post-T-DM1 therapy in Japanese patients with HER2-positive MBC. A short PFS with T-DM1 might affect the PFS with a treatment after T-DM1.

Median progression free survival (PFS) was 8,4 months (95% IC 6,9 – 9,9) and median overal survival (OS) was 23,6 months (95% IC 17,5 – 29,7). Overall Rate Response (ORR) was 42%....T-DM1 was an effective and well-tolerated treatment in routine clinical practice in patients with HMBC after PTT.

Between June 15, 2014 and January 31, 2020 we identified HER2+ (IHC: 3+ or 2+/FISH amplified) mBC pts treated with T-DM1...74 pts received T-DM1: Cohort T n = 34 (all females, median age = 52,7), Cohort PT n = 40 (39 females, 1 male, median age = 52,2)....Median progression- free survival was 10,2 in Cohort T and 3,7 months in Cohort PT.

This study enrolled consecutive patients who met eligibility criteria; Japanese female patients with HER2+ mBC...Of 205 patients who were treated with T-DM1 at five institutions, 138 patients were enrolled and 128 patients were included in the analysis (data-cut off: Jul 31 2019)...In the 111 patients with measurable lesions, ORR was 22.5% (95% CI: 15.1–31.4). The median rwPFS was 5.7 months (95% CI: 4.8–6.9), median TTF 5.6 months (95% CI: 4.6–6.4), median OS 22.8 months (95% CI: 18.2–32.4), and the CBR was 47.7% (95% CI: 38.8–56.7) in the 128 patients.

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….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).

Here, we report a case of HER2 positive metastatic breast cancer on a woman in her late 30s, with remission for over 3 years under second-line treatment with ado-trastuzumab emtansine…

A 41-year-old female presented with a huge breast lump and massive lymphadenopathy, which was diagnosed as HER2-positive, unresectable, locally advanced BC. The first treatment, consisting of docetaxel, trastuzumab and pertuzumab, had only a limited and temporary effect, with subsequent mass regrowth. After initiation of the second treatment, trastuzumab emtansine(TDM1), the mass gradually shrank, and mastectomy and axillary lymphadenectomy were performed successfully.

This patient was diagnosed with metastatic HER2 positive breast cancer...Patient's personal beliefs led her to choose a therapy that is currently a second-line: Ado-trastuzumab emtansine. She was able to achieve full remission.

The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays….MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro....Trastuzumab-MCC-DM1 was found effective against HER2+ tumors.