scholarly journals Case Report: Addition of PD-1 Antibody Camrelizumab Overcame Resistance to Trastuzumab Plus Chemotherapy in a HER2-Positive, Metastatic Gallbladder Cancer Patient

2022 ◽  
Vol 12 ◽  
Author(s):  
Li Wang ◽  
Xiaomo Li ◽  
Yurong Cheng ◽  
Jing Yang ◽  
Si Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Gallbladder Cancer ◽  
Standard Of Care ◽  
Her2 Positive ◽  
Limited Efficacy ◽  
Clinical Challenge ◽  
Frontline Treatment ◽  
Resistance To Chemotherapy ◽  
Positive Breast Cancer

HER2 amplification/overexpression is a common driver in a variety of cancers including gallbladder cancer (GBC). For patients with metastatic GBC, chemotherapy remains the standard of care with limited efficacy. The combination of HER2 antibody trastuzumab plus chemotherapy is the frontline treatment option for patients with HER2-positive breast cancer and gastric cancer. Recently, this regime also showed antitumor activity in HER2-positive GBC. However, resistance to this regime represents a clinical challenge. Camrelizumab is a novel PD-1 antibody approved for Hodgkin lymphoma and hepatocellular carcinoma in China. In this study, we presented a HER2-positive metastatic GBC patient who was refractory to trastuzumab plus chemotherapy but experienced significant clinical benefit after the addition of camrelizumab. Our case highlights the potential of immunotherapy in combination with HER2-targeted therapy in HER2-positive GBC. We also demonstrated that two immune-related adverse events (irAEs) associated with camrelizumab can be managed with an anti-VEGF agent apatinib. This case not only highlights the importance of irAE management in patients treated with camrelizumab, but also demonstrates the potential of PD-1 antibody plus trastuzumab in HER2-positive GBC patients who have developed resistance to chemotherapy and trastuzumab-based targeted therapy.

scholarly journals Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3540
Author(s):  
Hamid Maadi ◽  
Mohammad Hasan Soheilifar ◽  
Won-Shik Choi ◽  
Abdolvahab Moshtaghian ◽  
Zhixiang Wang
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Cancer Patients ◽  
Mechanism Of Action ◽  
Mechanisms Of Action ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Insight Into ◽  
Positive Breast Cancer

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened a new avenue to treat patients with HER2-positive breast cancer and other types of cancer, some patients are not responsive or become resistant to this treatment. So far, several mechanisms have been suggested for the mode of action of trastuzumab; however, the findings regarding these mechanisms are controversial. In this review, we aimed to provide a detailed insight into the various mechanisms of action of trastuzumab.

scholarly journals CLINICAL CASE OF SUCCESFUL APPLICATION OF KADSYLA APPLICATION IN METASTATIC HER2 POSITIVE BREAST CANCER

2017 ◽  
pp. 56-58
Author(s):  
D. D. Sakaeva
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Clinical Case ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Pet Ct ◽  
Positive Breast Cancer

A clinical case of trastuzumab emtansine in therapy line 4 in patient with metastatic HER2positive breast cancer is provided. After 10  courses of targeted therapy by the drug a complete  response to the therapy was obtained. By results of PET CT conducted in the period from December 2015  to September 2017 the complete response is preserved.

scholarly journals Use of HER2-Directed Therapy in Metastatic Breast Cancer and How Community Physicians Collaborate to Improve Care

2020 ◽  
Vol 9 (6) ◽  
pp. 1984 ◽  
Author(s):  
Joanne E. Mortimer ◽  
Laura Kruper ◽  
Mary Cianfrocca ◽  
Sayeh Lavasani ◽  
Sariah Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Standard Of Care ◽  
Research Network ◽  
Her2 Positive ◽  
Community Partners ◽  
Significant Prolongation ◽  
Positive Breast Cancer

The development of new HER2-directed therapies has resulted in a significant prolongation of survival for women with metastatic HER2-positive breast cancer. Discoveries in the laboratory inform clinical trials which are the basis for improving the standard of care and are also the backbone for quality improvement. Clinical trials can be completed more rapidly by expanding trial enrollment to community sites. In this article we review some of the challenges in treating metastatic breast cancer with HER2-directed therapies and our strategies for incorporating our community partners into the research network.

Safety of chemoradiotherapy in combination with targeted therapy in patients with locally advanced HER2-positive breast cancer

2017 ◽  
Vol 6 (4) ◽  
pp. 14
Author(s):  
A. S. Belokhvostova ◽  
I. P. Aslanidi ◽  
Yu. A. Ragulin ◽  
T. V. Pekshina ◽  
A. B. Orkina ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Locally Advanced ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

scholarly journals Systemic targeted therapy for her2-positive early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

2014 ◽  
Vol 22 ◽  
pp. 114 ◽  
Author(s):  
M. Mates ◽  
G.G. Fletcher ◽  
O.C. Freedman ◽  
A. Eisen ◽  
S. Gandhi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Targeted Therapy ◽  
Adjuvant Chemotherapy ◽  
Her2 Positive ◽  
National Surgical Adjuvant Breast ◽  
Her2 Positive Breast Cancer ◽  
International Research Group ◽  
Bowel Project ◽  
Positive Breast Cancer

BackgroundThis systematic review addresses the question “What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)–positive breast cancer?”MethodsThe medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched.ResultsSixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47).ConclusionsTaking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.

scholarly journals Pathologic and molecular responses to neoadjuvant trastuzumab and/or lapatinib from a phase II randomized trial in HER2-positive breast cancer (TRIO-US B07)

2020 ◽  
Author(s):  
Sara A Hurvitz ◽  
Jennifer L Caswell-Jin ◽  
Katherine L McNamara ◽  
Jason Zoeller ◽  
Gregory R Bean ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Targeted Therapy ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Early Assessment ◽  
Her2 Positive ◽  
Immune Infiltrate ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

In this neoadjuvant trial (TRIO-US B07), participants with early-stage HER2-positive breast cancer (N=128) were randomized to receive trastuzumab (T), lapatinib (L), or both (TL) as HER2-targeted therapy, with each participant given one cycle of this designated anti-HER2 therapy alone followed by six cycles of standard combination chemotherapy with the same anti-HER2 therapy. We observed similar pathologic complete response (pCR) rates between T and TL, and a lower pCR rate with L. Higher-level amplification of HER2 and hormone receptor-negative status were associated with a higher pCR rate. Higher pre-treatment immune infiltrate trended toward higher pCR rate in T-treated groups, and greater HR expression correlated with lower immune infiltrate. Large shifts in tumor, immune, and stromal gene expression occurred after one cycle of HER2-targeted therapy. In contrast to pCR rates, the L-containing arms exhibited greater proliferation reduction than T at this timepoint. Immune expression signatures increased in all arms after one cycle of HER2-targeted therapy, decreasing again by the time of surgery. Our results inform approaches to early assessment of sensitivity to anti-HER2 therapy and shed light on the role of the immune microenvironment in response to HER2-targeted agents.

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.

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