Abstract OT3-06-01: Phase Ib clinical trial of coPANlisib in combination with Trastuzumab emtansine (T-DM1) in pre-treated unresectable locally advanced or metastatic HER2-positive breAst cancer (BC) “PANTHERA”-CTRIAL-IE 17-13

2019 ◽  
Author(s):  
A Hassan ◽  
G Gullo ◽  
S O'Reilly ◽  
M Ruiz-Borrego ◽  
S Toomey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Locally Advanced ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Phase Ib ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

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

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.

Trastuzumab emtansine (T-DM1) and ribociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 (CDK 4/6), for patients with metastatic HER2-positive breast cancer: Phase 1b clinical trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS1106-TPS1106 ◽  
Author(s):  
Laura Spring ◽  
Shom Goel ◽  
Dejan Juric ◽  
Steven J. Isakoff ◽  
Stephanie Haddad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Metastatic Breast Cancer ◽  
Objective Response ◽  
Metastatic Breast ◽  
Clinical Activity ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

TPS1106 Background: Despite the availability of multiple effective therapies, most patients with metastatic HER2-positive breast cancer will experience disease progression and death. While traditionally the focus has been targeting the HER receptor family itself, combinations involving targets downstream of the HER2 pathway, particularly CDK 4/6, could potentially enhance therapeutic efficacy. In pre-clinical models of acquired resistance to HER2-targeted therapies, inhibition of CDK4/6 has been shown to result in tumor inhibition. Trial Design: This phase Ib, single arm, open-label clinical trialis investigating the combination of Trastuzumab emtansine (T-DM1) and the CDK4/6 inhibitor, ribociclib (LEE011). Eligible patients include patients age ≥ 18 years with HER2-positive metastatic breast cancer. Prior treatment with at least one regimen containing trastuzumab and a taxane is required. Ribociclib is given orally for two weeks of a 21-day cycle (days 8-21), with T-DM1 given at standard dose every 3 weeks on day 1. Trial Objectives: 1. To estimate the MTD and/or RP2D of ribociclib in combination with T-DM1. 2. To assess the safety and tolerability of ribociclib in combination with T-DM1. 3. To explore the clinical activity of T-DM1 and ribociclib in HER2-positive metastatic breast cancer. 4. To assess potential biomarkers of response to ribociclib in combination with T-DM1. Statistical Methods: A standard 3+3 dose escalation design is being used to evaluate various doses of ribociclib in combination with T-DM1 to determine the maximum tolerated dose (MTD) and/or recommended phase-2 dose (RP2D). Once MTD/RP2D is determined there will be a dose-expansion cohort (N = l5) to confirm the safety profile and evaluate preliminary evidence of efficacy, including objective response rate (ORR) by RECIST 1.1 and progression-free survival (PFS). Clinical trial information: NCT02657343.

Trial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS1102-TPS1102
Author(s):  
Patricia LoRusso ◽  
Mary Josephine Paula Pilat ◽  
Cesar Augusto Santa-Maria ◽  
Roisin M. Connolly ◽  
Erin Elizabeth Roesch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Dna Repair ◽  
Phase Ii ◽  
Locally Advanced ◽  
Parp Inhibition ◽  
Her2 Positive ◽  
Open Label ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

TPS1102 Background: While immunostimulatory therapies have shown great success, a major challenge remains identification of mechanisms to effectively treat the majority of patients with so-called "non-inflamed" tumors lacking marked lymphocyte infiltration and PD-L1 expression. The DNA repair proficiency of a tumor may impact its potential for immune recognition and sensitivity to immune checkpoint blockade. Preclinically, PARP inhibition in HDR-deficient tumors has been shown to trigger antitumor immunity through a STING-dependent antitumor immune response. Effects of PARP inhibitors were augmented when combined with PD-1 blockade. We hypothesize that enhanced DNA damage and cell death induced by PARP inhibition in tumors with homology directed repair (HDR) deficiency will enhance adaptive anti-tumor immune responses and increase sensitivity to PD-1 axis blockers. Methods: This is a randomized, open-label phase II clinical trial exploring the PARP inhibitor olaparib either alone or in combination with the anti-PD-L1 human monoclonal antibody atezolizumab in BRCA1/2 mutated locally advanced or metastatic non-HER2-positive breast cancer. HDR deficiency is defined as the presence of deleterious BRCA 1/2 mutations. Randomization occurs in a 1:1 fashion to two arms: (1) olaparib 300 mg PO bid continuously in 21-day cycles or (2) olaparib 300 mg PO bid continuously in combination with atezolizumab 1200 IV every 3 weeks in 21-day cycles. Patients undergo baseline evaluations and pre-treatment biopsy within 2 weeks of starting therapy. Repeat biopsies are required at the time of first tumor assessment scan (6 weeks from the start of treatment) and in the event of disease progression. Correlative studies, including detailed analysis of the genomic profile and tumor immune contexture, will be performed at each biopsy time point. The primary objective is to compare progression free survival between the study arms. If progression occurs on the olaparib monotherapy arm, cross-over to the combination arm is allowed. This study began enrolling in August 2018; 47 of the planned 72 patients have been registered. Clinical trial information: NCT02849496 .

scholarly journals 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 ◽  
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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