Beyond Trastuzumab and Lapatinib: New Options for HER2-Positive Breast Cancer

2013 ◽  
pp. e2-e11
Author(s):  
Dimitrios Zardavas ◽  
David Cameron ◽  
Ian Krop ◽  
Martine Piccart
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Molecular Subtype ◽  
Targeted Agents ◽  
Her2 Positive ◽  
Clinical Issue ◽  
Her2 Positive Breast Cancer ◽  
Metastatic Setting ◽  
Positive Breast Cancer

HER2-positive breast cancer (BC) constitutes a molecular subtype of the disease with an aggressive biologic behavior. Trastuzumab revolutionized the treatment of this disease, changing its natural history. Lapatinib is active in the metastatic setting, approved for patients who were pretreated with trastuzumab. However, resistance to anti-HER2 agents is a major clinical issue, occurring in both early-stage and advanced disease, and new treatment options are clearly needed. An abundance of HER2-targeted agents are being clinically developed: monoclonal antibodies, small molecule inhibitors, and antibody drug conjugates (ADC). Combining HER2-targeted agents in regimens of dual HER2 blockade has already reached clinical practice in the metastatic setting, confirming the preclinical efficacy of enhanced HER2 inhibition. Promising results have been generated in the neoadjuvant setting, and large randomized trials are seeking evidence for dual HER2 blockade in the adjuvant setting. ADC represent another hope for improved treatment outcomes of HER2-positive BC, as exemplified by the positive results of clinical trials employing trastuzumab-DM1 (trastuzumab emtansine, T-DM1). Moreover, an understanding of the molecular mechanisms mediating resistance to HER2 blockade has opened new therapeutic avenues, with several targeted agents entering clinical trials. This paper presents the clinical data of the HER2-targeted agents under development, as well as an overview of the biologic rationale for the development of agents aimed at circumventing anti-HER2 resistance.

scholarly journals THER-01. Targeted therapy and intracranial metastatic disease: a population-based retrospective cohort study

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii12-iii12
Author(s):  
Anders Erickson ◽  
Steven Habbous ◽  
Frances Wright ◽  
Aisha Lofters ◽  
Katarzyna Jerzak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Clinical Trials ◽  
Targeted Therapy ◽  
Targeted Therapies ◽  
Retrospective Cohort ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Intracranial Metastatic Disease ◽  
Positive Breast Cancer

Abstract Background Targeted therapies have been hypothesized to prolong survival in the management of patients with intracranial metastatic disease (IMD), but, paradoxically, to increase IMD incidence by improving systemic disease control and prolonging survival from the primary tumor. The real-world benefits of targeted therapy in management of patients with IMD are unclear, as clinical trials have excluded patients with IMD and lacked endpoints reporting intracranial outcomes. Methods This retrospective cohort study included all patients in Ontario, Canada, diagnosed with IMD from 2005 to 2018 with primary diagnoses of breast cancer, lung or bronchus cancer, or melanoma, and control patients matched by primary disease without IMD. Kaplan-Meier and multivariable Cox regression analyses were performed to compare overall survival (OS) between patient sub-cohorts divided by primary disease and stratified by targeted therapy receipt or IMD status. Results Post-IMD targeted therapy was associated with prolonged OS in patients with HER2-positive breast cancer (HR 0.41; 95% CI, 0.33–0.5), EGFR-positive lung cancer (HR 0.28; 95% CI, 0.23–0.34), and BRAF-positive melanoma (HR 0.2; 95% CI, 0.14–0.29), compared to those who did not receive post-IMD targeted therapy. Presence of IMD was associated with shorter OS in patients with metastatic HER2-positive breast cancer (HR 1.8; 95% CI, 1.56–2.08) and metastatic EGFR-positive lung cancer (HR 1.22; 95% CI, 1.08–1.39) but not metastatic BRAF-positive melanoma (HR 1.11; 95% CI, 0.77–1.61), compared to those without IMD. Conclusions Our findings show that real-world use of targeted therapies was associated with prolonged OS in patients with IMD in the setting of HER2-positive breast cancer, EGFR-positive lung cancer, and BRAF-positive melanoma. Inclusion of patients with IMD in clinical trials and use of endpoints that interrogate IMD will be critical to determine the role of targeted therapies in the management of patients with IMD.

Clinical utility of SERUM extracelullar domain of HER2 receptor (ECD) in HER2-positive breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12086-e12086
Author(s):  
Ariadna Gasol Cudós ◽  
Serafin Morales Murillo ◽  
Joel Veas Rodriguez ◽  
Carles Canosa Morales ◽  
Jordi Melé Olivé ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Metastatic Setting ◽  
Positive Breast Cancer

e12086 Background: Although ECD expression was validated as tumor marker years ago, it is not used in daily clinical practice even if a prognostic value was demonstrated in some trials. Methods: In our single institution, during January 2013-2019, ECD was analyzed in a series of HER2 positive breast cancer patients; 71 in early or locally-advanced and 45 in metastatic setting. Results: In the metastatic cohort, median ECD expression was of 28 ng/ml (6,5-350), thus 10 (22%) patients had lower levels than threshold of 15ng/ml. No correlation was found between ECD expression and other clinicopathological variables. No association was found with overall survival however in patients with metastases at diagnosis higher ECD expression was correlated with a short overall survival (25 vs 54 months). Higher levels of ECD decreased according to good response to treatment. Median ECD expression was of 12ng/ml (3,6-97) in non-metastatic setting, however only 11 (15%) patients had elevated levels ( > 15ng/ml). Estrogen receptor and ki67 expression were not correlated with ECD levels. Median ECD expression in tumors > 5cm was 21,87 ng/ml versus 12ng/ml in smaller tumors (p = 0,006); in nodal involvement median ECD was 16,77 ng/ml versus 12,05 without affectation (p = 0,09). Patients with ECD higher than 10 ng/ml had a 55% pathologic complete response (pCR) versus 25% if less than 10ng/ml (OR 3.68, p = 0.027). Interestingly, none of tumors > 5cm and ECD < 10ng/ml achieved a pCR. Conclusions: Higher levels of ECD were observed in the metastatic setting and their decreased levels during treatment was correlated with response. In early and locally-advanced setting higher levels were found in larger tumors; and also these tumors had better response than lower levels of ECD. ECD could be used as a monitoring tool in the metastatic scenario and as a predictive factor of response in the neoadjuvant setting, specifically in tumors > 5cm.

Trastuzumab biosimilar (Kanjinti) in breast cancer patients: One-center retrospective observational study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13015-e13015
Author(s):  
Agnieszka I. Jagiello-Gruszfeld ◽  
Izabela Lemanska ◽  
Elzbieta Brewczynska ◽  
Katarzyna Pogoda ◽  
Roman Dubianski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Real World ◽  
Safety Profile ◽  
Safety Data ◽  
Her2 Positive ◽  
Reference Drug ◽  
Her2 Positive Breast Cancer ◽  
Metastatic Setting ◽  
Positive Breast Cancer

e13015 Background: The switch of anti-HER2 therapy from the reference drug Herceptin to a biosimilar has presented challenges to the clinics. Real world data on trastuzumab biosimilars are very limited or not available. In our clinic we perform observational retrospective study to confirm safety and efficacy Kanjinti. Methods: 195 patients (pts) with HER2-positive breast cancer were treated with Kanjinti from Jul.18. 2018 to Jan.29.2020. Cardiac events (↓LVEF) and other unexpected or serious adverse events were monitored in all pts. 34 pts received carboplatin, docetaxel pertuzumab and trastuzumab biosimilar in neoadjuvant setting, 99 received trastuzumab biosymilar in monotherapy or with other cytostatic drugs in neoadjuvant or adjuvant setting, and 62 received docetaxel, pertuzumab and Kanjinti in metastatic setting. Results: Pertuzumab was used in combination with Kanjinti in 49% of pts (32% in the 1st. line of palliative tretment and 17% in the neoadjuvant settings, respectively).Switching from Herceptin to Kanjinti was observed in 65% of MBC patients and 37% of EBC patients. Switching was done at a median of 4th cycle. 6 patients had a decline in LVEF. No other trastuzumab related adverse events was observed. Conclusions: The management of HER2 positive breast cancer in our clinic follows the international recommendations. This is the first real world safety data of Kanjinti from Poland. The 12-month follow-up treatment with Kanjinti an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Kanjinti or Kanjinti combined with pertuzumab, the safety profile was similar to that previously reported in other studies.

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