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Author: Cornflower This article is published by Yimaitong authorized by the author, please do not reprint without authorization.
Introduction HER2-positive breast cancer accounts for about 20% to 25% of all breast cancers.
The high expression of HER2 protein predicts the acceleration of cancer cell growth, and the overexpression of HER2 is related to the metastasis of cancer cells, often indicating a poor prognosis.
Therefore, how to improve the therapeutic effect of HER2-positive breast cancer patients has important clinical significance.
The advent of trastuzumab opened a new chapter in the treatment of HER2-positive breast cancer.
The NOAH study established the status of trastuzumab in the neoadjuvant treatment of Her2-positive locally advanced breast cancer.
Compared with chemotherapy alone, it increased the pathological remission rate (pCR) by 2 times.
This significant effect caused the study to be terminated early.
Subsequent studies have further confirmed the efficacy of trastuzumab, which can not only significantly increase the pCR rate, but also prolong the overall survival of patients.
At present, for patients with HER2-positive early breast cancer, 6 to 8 rounds of adjuvant chemotherapy + 1 year trastuzumab have become the standard of adjuvant treatment.
However, 1 year of trastuzumab treatment may bring economic expenses, time costs, and side effects of the drug itself, and long-term application will bring about primary and secondary drug resistance1.
So, can the application time of trastuzumab be shortened? A study called ShortHER at the ESMO breast cancer annual meeting held online on May 5-8 gave the answer.
Study Introduction ShortHER is an Italian multi-center randomized phase III non-inferiority clinical study.
The purpose is to prove that trastuzumab is non-inferior to one year after a 9-week course of adjuvant therapy.
The patients included in the study were HER2-positive, lymph node-positive, or lymph node-negative breast cancer patients.
The trial randomly divided 1,254 HER2-positive early breast cancer patients into chemotherapy-adjuvant 9-week trastuzumab group vs 1-year trastuzumab group.
The research preset non-inferiority margin is 1.
29.
The 5-year DFS results have been published at the 2018 ESMO Conference 2: 88% in the standard treatment group, 85% in the short-term treatment group, and the upper limit of the HR confidence interval is 1.
42, which exceeds the preset 1.
29.
Therefore, it is not possible to prove adjuvant treatment for 9 weeks Trastuzumab is non-inferior to the 1-year standard treatment.
However, the 9-week dosing regimen reduces the risk of severe cardiotoxicity, and patients who have a cardiac event during treatment can consider options.
The ESMO annual meeting analyzed the overall survival rate (OS) based on HR status and three risk categories, and updated the disease-free survival rate (DFS)3.
After a median follow-up of 8.
7 years, patients who received trastuzumab for 1 year had a 5-year DFS of 87.
9%, while those who received trastuzumab for 9 weeks had a DFS of 85.
8% (HR = 1.
09; 90% CI: 0.
88) -1.
35); In addition, the 5-year OS rate of both groups was 95.
1% (HR=1.
18; 90%CI: 0.
86-1.
62).
The researchers stratified according to tumor size and lymph node status, and divided the enrolled patients into three groups of high, medium and low risk.
T≤2cm and negative lymph node was defined as low-risk group, T≤2cm any lymph node status or T>2cm and N0- 3 Defined as a middle-risk group, T>2cm and N4+ is defined as a high-risk group.
Low-risk group (accounting for 37.
2% of the study population) HR 0.
91 (90% CI 0.
60-1.
38), 5-year DFS is 91% in both groups; medium-risk group (accounting for 46.
7% of the study population) HR 0.
88 (90% CI 0.
63-1.
21), the 5-year DFS was 89% vs 88%; the high-risk group (accounting for 15.
2% of the study population) had an HR 2.
06 (90% CI 1.
36-3.
13), and the 5-year DFS was 82% vs 64%.
109 deaths have been reported (58 in the short treatment period and 51 in the long treatment period).
The 9-year OS accounted for 90% in the short treatment period group and 91% in the long treatment period group (HR 1.
18; 90% CI 0.
86-1.
62).
In addition, the researchers also found an association between longer treatment time and a higher incidence of cardiac events.
In the long-term treatment group, the incidence of grade 2 cardiac events was 13.
1%, while in the short-term treatment group it was 4.
3%.
The updated DFS and OS analysis of the ShortHER trial data confirmed the good long-term efficacy of trastuzumab for 9 weeks in patients with low- and medium-risk factors, but for high-risk groups, a short course of trastuzumab treatment will have worse long-term survival, one year The trastuzumab treatment is still the standard regimen.
Summary The use of trastuzumab has significantly improved the cure rate of HER2-positive breast cancer, which is a major advancement in medicine.
However, side effects of drugs are an inevitable problem, and cardiotoxicity is the main problem in the use of trastuzumab.
Shortening the treatment time can reduce toxic side effects, time cost and economic burden.
Researchers have been exploring whether a shorter treatment time is feasible, and related studies have been disturbed and controversial.
After a series of short-term treatment studies, the researchers tried to screen the people who benefited from short-term targeted therapy through stratified analysis of clinical characteristics or bio-predictive markers.
The ShortHER research results announced at this ESMO conference are a good example.
For high-risk populations, trastuzumab administration for 1 year is still the standard treatment plan, but for most real-world patients with HER2-positive early breast cancer, downgrading treatment is a reasonable choice.
The update of the results of this study provides evidence-based medicine for the first time to shorten the treatment time of trastuzumab.
References: 1.
Li G, Guo J, Shen BQ, et al.
Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells.
Mol Cancer Ther.
2018;17(7):1441-1453.
2.
Conte P, Frassoldati A, Bisagni G,et al.
9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study.
Ann Oncol 2018;DOI:10.
1093/annonc/mdy414.
3.
Nine weeks vs 1-year adjuvant trastuzumab: Long term outcomes of the ShortHER randomised trial.
Annals of Oncology (2021) 32 (suppl_2): S37-S47.
10.
1016/annonc/annonc504.
Introduction HER2-positive breast cancer accounts for about 20% to 25% of all breast cancers.
The high expression of HER2 protein predicts the acceleration of cancer cell growth, and the overexpression of HER2 is related to the metastasis of cancer cells, often indicating a poor prognosis.
Therefore, how to improve the therapeutic effect of HER2-positive breast cancer patients has important clinical significance.
The advent of trastuzumab opened a new chapter in the treatment of HER2-positive breast cancer.
The NOAH study established the status of trastuzumab in the neoadjuvant treatment of Her2-positive locally advanced breast cancer.
Compared with chemotherapy alone, it increased the pathological remission rate (pCR) by 2 times.
This significant effect caused the study to be terminated early.
Subsequent studies have further confirmed the efficacy of trastuzumab, which can not only significantly increase the pCR rate, but also prolong the overall survival of patients.
At present, for patients with HER2-positive early breast cancer, 6 to 8 rounds of adjuvant chemotherapy + 1 year trastuzumab have become the standard of adjuvant treatment.
However, 1 year of trastuzumab treatment may bring economic expenses, time costs, and side effects of the drug itself, and long-term application will bring about primary and secondary drug resistance1.
So, can the application time of trastuzumab be shortened? A study called ShortHER at the ESMO breast cancer annual meeting held online on May 5-8 gave the answer.
Study Introduction ShortHER is an Italian multi-center randomized phase III non-inferiority clinical study.
The purpose is to prove that trastuzumab is non-inferior to one year after a 9-week course of adjuvant therapy.
The patients included in the study were HER2-positive, lymph node-positive, or lymph node-negative breast cancer patients.
The trial randomly divided 1,254 HER2-positive early breast cancer patients into chemotherapy-adjuvant 9-week trastuzumab group vs 1-year trastuzumab group.
The research preset non-inferiority margin is 1.
29.
The 5-year DFS results have been published at the 2018 ESMO Conference 2: 88% in the standard treatment group, 85% in the short-term treatment group, and the upper limit of the HR confidence interval is 1.
42, which exceeds the preset 1.
29.
Therefore, it is not possible to prove adjuvant treatment for 9 weeks Trastuzumab is non-inferior to the 1-year standard treatment.
However, the 9-week dosing regimen reduces the risk of severe cardiotoxicity, and patients who have a cardiac event during treatment can consider options.
The ESMO annual meeting analyzed the overall survival rate (OS) based on HR status and three risk categories, and updated the disease-free survival rate (DFS)3.
After a median follow-up of 8.
7 years, patients who received trastuzumab for 1 year had a 5-year DFS of 87.
9%, while those who received trastuzumab for 9 weeks had a DFS of 85.
8% (HR = 1.
09; 90% CI: 0.
88) -1.
35); In addition, the 5-year OS rate of both groups was 95.
1% (HR=1.
18; 90%CI: 0.
86-1.
62).
The researchers stratified according to tumor size and lymph node status, and divided the enrolled patients into three groups of high, medium and low risk.
T≤2cm and negative lymph node was defined as low-risk group, T≤2cm any lymph node status or T>2cm and N0- 3 Defined as a middle-risk group, T>2cm and N4+ is defined as a high-risk group.
Low-risk group (accounting for 37.
2% of the study population) HR 0.
91 (90% CI 0.
60-1.
38), 5-year DFS is 91% in both groups; medium-risk group (accounting for 46.
7% of the study population) HR 0.
88 (90% CI 0.
63-1.
21), the 5-year DFS was 89% vs 88%; the high-risk group (accounting for 15.
2% of the study population) had an HR 2.
06 (90% CI 1.
36-3.
13), and the 5-year DFS was 82% vs 64%.
109 deaths have been reported (58 in the short treatment period and 51 in the long treatment period).
The 9-year OS accounted for 90% in the short treatment period group and 91% in the long treatment period group (HR 1.
18; 90% CI 0.
86-1.
62).
In addition, the researchers also found an association between longer treatment time and a higher incidence of cardiac events.
In the long-term treatment group, the incidence of grade 2 cardiac events was 13.
1%, while in the short-term treatment group it was 4.
3%.
The updated DFS and OS analysis of the ShortHER trial data confirmed the good long-term efficacy of trastuzumab for 9 weeks in patients with low- and medium-risk factors, but for high-risk groups, a short course of trastuzumab treatment will have worse long-term survival, one year The trastuzumab treatment is still the standard regimen.
Summary The use of trastuzumab has significantly improved the cure rate of HER2-positive breast cancer, which is a major advancement in medicine.
However, side effects of drugs are an inevitable problem, and cardiotoxicity is the main problem in the use of trastuzumab.
Shortening the treatment time can reduce toxic side effects, time cost and economic burden.
Researchers have been exploring whether a shorter treatment time is feasible, and related studies have been disturbed and controversial.
After a series of short-term treatment studies, the researchers tried to screen the people who benefited from short-term targeted therapy through stratified analysis of clinical characteristics or bio-predictive markers.
The ShortHER research results announced at this ESMO conference are a good example.
For high-risk populations, trastuzumab administration for 1 year is still the standard treatment plan, but for most real-world patients with HER2-positive early breast cancer, downgrading treatment is a reasonable choice.
The update of the results of this study provides evidence-based medicine for the first time to shorten the treatment time of trastuzumab.
References: 1.
Li G, Guo J, Shen BQ, et al.
Mechanisms of Acquired Resistance to Trastuzumab Emtansine in Breast Cancer Cells.
Mol Cancer Ther.
2018;17(7):1441-1453.
2.
Conte P, Frassoldati A, Bisagni G,et al.
9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study.
Ann Oncol 2018;DOI:10.
1093/annonc/mdy414.
3.
Nine weeks vs 1-year adjuvant trastuzumab: Long term outcomes of the ShortHER randomised trial.
Annals of Oncology (2021) 32 (suppl_2): S37-S47.
10.
1016/annonc/annonc504.
