Ignite Creation Date:
2024-05-06 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 1:54 PM
Study NCT ID:
NCT04722718
Status:
UNKNOWN
Last Update Posted:
2022-04-28
First Post:
2021-01-20
Brief Title:
Efficacy and Safety of Sintilimab and Apatinib Combined Chemotherapy in Breast Cancer
Sponsor:
Jiuda Zhao
Organization:
Affiliated Hospital of Qinghai University
Study Overview
Official Title:
Efficacy and Safety of Neoadjuvant Therapy With Sintilimab and Apatinib Combined Chemotherapy in Triple-negative Breast Cancer
Status:
UNKNOWN
Status Verified Date:
2021-05
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 The efficacy and safety of immunotherapy and antiangiotherapy in combination with chemotherapy in neoadjuvant therapy for triple-negative breast cancer TNBC were determined by the addition of sintilimab and apatinib to neoadjuvant chemotherapy
2 To clarify the breast-conserving rate toxicity difference in pathologic complete response pCR rate of patients with PD-L1 and PD-L1 - after neoadjuvant treatment of TNBC with immunotherapy and anti-vascular therapy combined with chemotherapy and the relationship between pCR rate of immunomodulated type IM and non-immunomodulated type patients in Fudan classification
3 Through post-treatment efficacy evaluation and safety analysis we provide new treatment strategies for TNBC patients increase the pCR rate of TNBC patients and ultimately improve the long-term survival of patients
2 To clarify the breast-conserving rate toxicity difference in pathologic complete response pCR rate of patients with PD-L1 and PD-L1 - after neoadjuvant treatment of TNBC with immunotherapy and anti-vascular therapy combined with chemotherapy and the relationship between pCR rate of immunomodulated type IM and non-immunomodulated type patients in Fudan classification
3 Through post-treatment efficacy evaluation and safety analysis we provide new treatment strategies for TNBC patients increase the pCR rate of TNBC patients and ultimately improve the long-term survival of patients
Detailed Description:
In the past decades the incidence of breast cancer in humans has continued to rise posing a huge threat to the lives and health of patients worldwide According to statistics released by the American Cancer SocietyIn 2019 there were more than 271000 new cases of breast cancer and about 42260 deaths in the United States As a highly heterogeneous disease breast cancer can be based on estrogen receptor ER progesterone receptor PR and human epidermal growth factor receptor 2 HER-2 and antigen Ki-67 is divided into several subtypes TNBC is one of the subtypes of breast cancer which is characterized by the lack of protein expression of ER PR and HER-2 Clinically TNBC is a very aggressive subtype of breast cancer accounting for about 12 to 17 of all breast cancers Due to its aggressiveness and lack of drug targets compared with other subtypes of breast cancer TNBC patients have a shorter overall survival OS and the median OS of metastatic TNBC is only 8-15 months Chemotherapy is still the main systemic treatment for TNBC but drug resistance develops rapidly and is poorly tolerated Therefore there is an urgent need to develop new treatment strategies for these patients
The clinical and molecular heterogeneity of TNBC is now well understood Gene expression analysis showed that immune markers androgen receptors mesenchymal phenotypes stem cell markers and basic markers are all related to TNBC subtypes With reference to previous studies according to the results of transcriptomics research and based on transcriptome data Chinas Fudan Classification divides TNBC into 4 subtypes 1 luminal androgen receptor LAR 2 Immunomodulatory IM 3 basal-like and immune-suppressed BLIS and 4 mesenchymal-like MES Possible therapeutic targets or biomarkers have been identified for each subtype
To date neoadjuvant chemotherapy has played an important role in the treatment of locally advanced TNBC patients Through neoadjuvant chemotherapy tumor shrinkage and stage reduction can improve the surgical radical cure rate and breast conserving rate Postoperative pCR rate is of great significance in predicting the prognosis of patients and those who achieve pCR tend to have better prognosis A meta-analysis of 52 studies showed that the availability of pCR for neoadjuvant therapy in TNBC patients was significantly associated with event-free survival EFS with a 5-year EFS of 90 in the pCR group and only 57 in tumor survivors HR018 The prognosis of non-pCR or drug-resistant patients is relatively poor and in order to reduce the recurrence and metastasis rate and improve the prognosis intensive chemotherapy is often needed Currently there is no standard treatment regimen for TNBC Previous studies have shown that the pCR rate of traditional anthracyclines followed by sequenzine therapy for TNBC can reach 25-40 but there are still nearly 20 patients with recent recurrence Therefore the optimization of TNBC treatment regimen is still a hot spot and difficulty in current clinical studies
In recent years platinum drugs have attracted more and more attention in the neoadjuvant therapy of TNBC due to their ability to significantly improve pCR rate Carboplatin can kill cancer cells by destroying their DNA Currently it has become an important neoadjuvant chemotherapy drug in the treatment of TNBC Studies have shown that adding the DNA damage agent carboplatin to the neoadjuvant regimen can improve the pCR rate of TNBC In 2020 the latest studies showed that carboplatin combined with nab-paclitaxel showed good anti-tumor activity and a high PCR rate of 48
In addition antiangiogenic therapy has been considered as a potential therapeutic strategy for patients with TNBC In 2008 bevacizumab was approved by the US Food and Drug Administration FDA for significantly increasing patients PFS in combination with chemotherapy Mesylate path is for our country to develop a new type of oral small molecule anti angiogenesis inhibitors mainly through highly selective inhibition of vascular endothelial growth factor receptor 2 VEGFR - 2 the activity of tyrosine kinase blocking vascular endothelial growth factor VEGF and its receptor signal transduction pathways thus potent inhibition of tumor angiogenesis play a role of anti-tumor In addition preclinical studies have shown that anti-angiogenic therapy can improve the sensitivity of anti-PD-1 PD-L1 therapy by increasing PD-L1 expression and CD8 T cell infiltration in the tumor microenvironment Therefore anti-angiogenic therapy may enhance the response to PD-1PD-L1 blockade and improve survival
Currently blocking of programmed death protein 1PD-1 and programmed death ligand 1PD-L1 is an attractive treatment option for TNBC since stromal infiltrating lymphocytes TILS and PD-L1 are associated with favorable outcomes for TNBC Impassion130 showed that first-line treatment with albumin paclitaxel combined with atzumab anti-PD-L1 antibody increased PFS by 22 months in patients with PD-L1 positive advanced TNBC and increased OS by 7 months compared with placebo plus albumin paclitaxel Therefore the combination of chemotherapy and immunotherapy was proved to be effective Meanwhile in 2020 Impassion031 and Keynote-522 published the results of two classic studies the pCR rate after immunotherapy combined with chemotherapy neoadjuvant therapy reached 58 and 648 respectively further confirming the high efficacy of immunotherapy combined with chemotherapy
TNBC as one of a kind of high heterogeneity of breast cancer subtypes its aggressive is strong postoperative recurrence occurred more transfer lack of effective treatment of molecular therapeutic targets endocrine therapy and its ehrs resistance - 2 treatment often invalid therefore compared with other subtypes of breast cancer TNBC after neoadjuvant chemotherapy to pCR has more significant prognostic value Currently there is no standard treatment for TNBC except traditional anthracycline and taxane chemotherapy regimens Therefore it is critical to optimize the neoadjuvant chemotherapy regimens for TNBC to increase the pCR rate and improve the long-term prognosis of patients
So far 6 clinical trials of apatinib combined with neoadjuvant chemotherapy for TNBC have been registered in China However there are no relevant reports on immunotherapy and antiangiogenesis therapy combined with chemotherapy in the neoadjuvant treatment of TNBC at home and abroad Based on the results of previous classic studies and preclinical studies the researchers initiated this clinical study to clarify the efficacy and safety of sintilimab and apatinib combined with chemotherapy in the neoadjuvant treatment of TNBC in order to provide treatment for TNBC patients Strategy
The clinical and molecular heterogeneity of TNBC is now well understood Gene expression analysis showed that immune markers androgen receptors mesenchymal phenotypes stem cell markers and basic markers are all related to TNBC subtypes With reference to previous studies according to the results of transcriptomics research and based on transcriptome data Chinas Fudan Classification divides TNBC into 4 subtypes 1 luminal androgen receptor LAR 2 Immunomodulatory IM 3 basal-like and immune-suppressed BLIS and 4 mesenchymal-like MES Possible therapeutic targets or biomarkers have been identified for each subtype
To date neoadjuvant chemotherapy has played an important role in the treatment of locally advanced TNBC patients Through neoadjuvant chemotherapy tumor shrinkage and stage reduction can improve the surgical radical cure rate and breast conserving rate Postoperative pCR rate is of great significance in predicting the prognosis of patients and those who achieve pCR tend to have better prognosis A meta-analysis of 52 studies showed that the availability of pCR for neoadjuvant therapy in TNBC patients was significantly associated with event-free survival EFS with a 5-year EFS of 90 in the pCR group and only 57 in tumor survivors HR018 The prognosis of non-pCR or drug-resistant patients is relatively poor and in order to reduce the recurrence and metastasis rate and improve the prognosis intensive chemotherapy is often needed Currently there is no standard treatment regimen for TNBC Previous studies have shown that the pCR rate of traditional anthracyclines followed by sequenzine therapy for TNBC can reach 25-40 but there are still nearly 20 patients with recent recurrence Therefore the optimization of TNBC treatment regimen is still a hot spot and difficulty in current clinical studies
In recent years platinum drugs have attracted more and more attention in the neoadjuvant therapy of TNBC due to their ability to significantly improve pCR rate Carboplatin can kill cancer cells by destroying their DNA Currently it has become an important neoadjuvant chemotherapy drug in the treatment of TNBC Studies have shown that adding the DNA damage agent carboplatin to the neoadjuvant regimen can improve the pCR rate of TNBC In 2020 the latest studies showed that carboplatin combined with nab-paclitaxel showed good anti-tumor activity and a high PCR rate of 48
In addition antiangiogenic therapy has been considered as a potential therapeutic strategy for patients with TNBC In 2008 bevacizumab was approved by the US Food and Drug Administration FDA for significantly increasing patients PFS in combination with chemotherapy Mesylate path is for our country to develop a new type of oral small molecule anti angiogenesis inhibitors mainly through highly selective inhibition of vascular endothelial growth factor receptor 2 VEGFR - 2 the activity of tyrosine kinase blocking vascular endothelial growth factor VEGF and its receptor signal transduction pathways thus potent inhibition of tumor angiogenesis play a role of anti-tumor In addition preclinical studies have shown that anti-angiogenic therapy can improve the sensitivity of anti-PD-1 PD-L1 therapy by increasing PD-L1 expression and CD8 T cell infiltration in the tumor microenvironment Therefore anti-angiogenic therapy may enhance the response to PD-1PD-L1 blockade and improve survival
Currently blocking of programmed death protein 1PD-1 and programmed death ligand 1PD-L1 is an attractive treatment option for TNBC since stromal infiltrating lymphocytes TILS and PD-L1 are associated with favorable outcomes for TNBC Impassion130 showed that first-line treatment with albumin paclitaxel combined with atzumab anti-PD-L1 antibody increased PFS by 22 months in patients with PD-L1 positive advanced TNBC and increased OS by 7 months compared with placebo plus albumin paclitaxel Therefore the combination of chemotherapy and immunotherapy was proved to be effective Meanwhile in 2020 Impassion031 and Keynote-522 published the results of two classic studies the pCR rate after immunotherapy combined with chemotherapy neoadjuvant therapy reached 58 and 648 respectively further confirming the high efficacy of immunotherapy combined with chemotherapy
TNBC as one of a kind of high heterogeneity of breast cancer subtypes its aggressive is strong postoperative recurrence occurred more transfer lack of effective treatment of molecular therapeutic targets endocrine therapy and its ehrs resistance - 2 treatment often invalid therefore compared with other subtypes of breast cancer TNBC after neoadjuvant chemotherapy to pCR has more significant prognostic value Currently there is no standard treatment for TNBC except traditional anthracycline and taxane chemotherapy regimens Therefore it is critical to optimize the neoadjuvant chemotherapy regimens for TNBC to increase the pCR rate and improve the long-term prognosis of patients
So far 6 clinical trials of apatinib combined with neoadjuvant chemotherapy for TNBC have been registered in China However there are no relevant reports on immunotherapy and antiangiogenesis therapy combined with chemotherapy in the neoadjuvant treatment of TNBC at home and abroad Based on the results of previous classic studies and preclinical studies the researchers initiated this clinical study to clarify the efficacy and safety of sintilimab and apatinib combined with chemotherapy in the neoadjuvant treatment of TNBC in order to provide treatment for TNBC patients Strategy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None