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In recent years, with the advancement of diagnosis and treatment and the emergence of targeted drugs and immunotherapy, more and more colorectal cancer patients have passed the five-year survival period and achieved longer survival benefits
.
Genetic testing has laid the foundation for the precise treatment of metastatic colorectal cancer
.
According to the mutation status of the gene, it can help doctors formulate the most suitable treatment and medication plan, so as to bring more survival benefits to patients with colorectal cancer
.
At the 2021 American Society of Clinical Oncology (ASCO) annual meeting, a number of research results on the first-line treatment of metastatic colorectal cancer (mCRC) were announced, providing important evidence for the precise diagnosis and treatment of colorectal cancer
.
MSI-H/dMMR mCRC: KEYNOTE-177 study final OS result (Abs3500) The KEYNOTE-177 study aims to evaluate pembrolizumab as a single agent versus standard treatment (FOLFOX or FOLFIRI chemotherapy ± targeting bevacizumab or cetrol) The efficacy and safety of first-line treatment of MSI-H/dMMR mCRC patients
.
The results of the second interim analysis of the study showed that the progression-free survival (PFS) of the pembrolizumab group was better than that of the control group
.
The final analysis result of the KEYNOTE-177 study on overall survival (OS) was announced at this ASCO annual meeting
.
A total of 307 MSI-H / dMMR mCRC patients with an ECOG PS score of 0 or 1 were included in the study.
The median follow-up time of the pembrolizumab group was 44.
5 months (36.
0-60.
3), while the median follow-up time of the control group was 44.
5 months (36.
0-60.
3).
The follow-up time was 44.
4 months (36.
2-58.
6)
.
60% of patients in the control group received PD-1/PD-L1 immune checkpoint inhibitor treatment after disease progression; the median OS of the K drug group had not yet reached, and the median OS of the control group was 36.
7 months, and the risk of death Reduced by 26% (HR 0.
74; 95% CI, 0.
53-1.
03; P=0.
0359); the K drug treatment group showed a trend of OS benefit, the 36-month OS rate was 61%, and the control group was 50%
.
· The median PFS of the K drug group was 16.
5 months, which was twice that of the control chemotherapy group (8.
2 months) (HR=0.
59; 95%CI: 0.
45~0.
79; P=0.
0002); the K drug group was finally determined to be objective The response rate (ORR) was 45.
1% (20 CR, 49 PR), and the control group was 33.
1% (6 CR, 45 PR); the median duration of response (DOR) in the K drug group did not reach (2.
3+ ~ 53.
5+) , The control group was 10.
6 months (2.
8 ~ 48.
3+); the incidence of treatment-related adverse events (TRAE) above grade 3 in the K drug group was 21.
6%, and the control group was 66.
4%
.
For the first-line treatment of patients with MSI-H/dMMR mCRC, pembrolizumab has better PFS than conventional chemotherapy, the incidence of TRAE is lower, and there is a trend to reduce the risk of death, which may be due to the higher proportion of chemotherapy groups ( 60%) of patients crossed over from chemotherapy to anti-PD-1/PD-L1 treatment, resulting in OS that did not reach a statistical difference
.
In summary, pembrolizumab should still be used as the standard regimen for the first-line treatment of MSI-H/dMMR mCRC
.
RAS wild-type mCRC: The DEEPER (JACCROCC-13) study (Abs3501) The three-drug FOLFOXIRI regimen combined with bevacizumab or cetuximab for the treatment of RAS wild-type mCRC has been shown in the TRIBE and VOLFI studies to compare with the two-drug combination The program has better early tumor regression (ETS) and depth of regression (DpR)
.
A study from Japan at this ASCO annual meeting compared the efficacy and safety of bevacizumab versus cetuximab combined with FOLFOXIRI for RAS wild-type mCRC
.
A total of 359 subjects were enrolled in the study, including 173 in the cetuximab group and 175 in the bevacizumab group
.
The median treatment cycle of the cetuximab group was 10 (range: 1-51), and the median treatment cycle of the bevacizumab group was 12 (range: 1-51)
.
The study reached the primary endpoint: the DpR of the cetuximab group was 57.
4%, the DpR of the bevacizumab group was 46.
0% (p = 0.
0010); the median DpR of the primary tumor on the left was 60.
3% and 46.
1% (p = .
0007); the DpR of the primary tumor on the right side was 50.
0% vs.
41.
2% (p = 0.
46)
.
The ETS rate and ORR of the cetuximab group were 77.
8% and 69.
1%, and the ETS rate and ORR of the bevacizumab group were 74.
6% and 71.
7%, and the difference was not statistically significant
.
The PFS and OS of all populations were 12.
7 months (95% CI 11.
5-14.
0) and 37.
6 months (95% CI 30.
8-43.
0), respectively
.
Studies have shown that mFOLFOXIRI combined with cetuximab as the first-line treatment of RAS wild-type mCRC is significantly better than mFOLFOXIRI combined with bevacizumab in terms of DpR, which can bring deeper tumor regression for patients with left bowel cancer
.
BRAF V600E mutant metastatic colorectal cancer: FIRE-4.
5 study (Abs3502) FIRE-4.
5 (AIO KRK-0116) study compared FOLFOXIRI combined with cetuximab or bevacizumab in the treatment of patients with BRAF V600E mutant mCRC Curative effect
.
A total of 107 patients from 90 German and 10 French research centers were included in the study.
They were randomly assigned to receive FOLFOXIRI combined with Cetuximab (72 cases) or FOLFOXIRI combined with Bevacizumab (35 cases) at a 2:1 ratio.
.
No new or unexpected toxic reactions were observed in the study
.
In the intent-to-treat (ITT) population: the ORR of the cetuximab group was 40.
3%, and the ORR of the bevacizumab group was 51.
4% (p=0.
28), which did not reach the primary study endpoint
.
The median PFS in the bevacizumab group was significantly longer than that in the cetuximab group (8.
3 months vs 6.
0 months; p=0.
03; HR 1.
75)
.
The median OS was 16.
8 months in the bevacizumab group and 14.
6 months in the cetuximab group (p=0.
67; HR 1.
16), and the difference was not statistically significant
.
The results of the two groups of patients with the left semi-primary tumor were similar, while the bevacizumab group of patients with the right semi-primary tumor had a better therapeutic effect trend
.
FIRE-4.
5 is the first prospective randomized study to study the efficacy of FOLFOXIRI combined with targeted therapy in the first-line treatment of BRAF V600E mutant mCRC patients
.
FOLFOXIRI combined with bevacizumab or cetuximab has similar curative effects, but there are differences in curative effect according to the site of the primary tumor, which is related to the heterogeneity of the BRAF V600E mutation subgroup of mCRC patients
.
References: 1.
Final overall survival for the phase III KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
ABSTRACT35002.
The randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13).
ABSTRACT35013.
Randomized study to investigate FOLFOXIRI plus either bevacizumab or cetuximab as first-line treatment of BRAF V600E-mutant mCRC: The phase-II FIRE-4.
5 study (AIO KRK-0116).
ABSTRACT3502
.
Genetic testing has laid the foundation for the precise treatment of metastatic colorectal cancer
.
According to the mutation status of the gene, it can help doctors formulate the most suitable treatment and medication plan, so as to bring more survival benefits to patients with colorectal cancer
.
At the 2021 American Society of Clinical Oncology (ASCO) annual meeting, a number of research results on the first-line treatment of metastatic colorectal cancer (mCRC) were announced, providing important evidence for the precise diagnosis and treatment of colorectal cancer
.
MSI-H/dMMR mCRC: KEYNOTE-177 study final OS result (Abs3500) The KEYNOTE-177 study aims to evaluate pembrolizumab as a single agent versus standard treatment (FOLFOX or FOLFIRI chemotherapy ± targeting bevacizumab or cetrol) The efficacy and safety of first-line treatment of MSI-H/dMMR mCRC patients
.
The results of the second interim analysis of the study showed that the progression-free survival (PFS) of the pembrolizumab group was better than that of the control group
.
The final analysis result of the KEYNOTE-177 study on overall survival (OS) was announced at this ASCO annual meeting
.
A total of 307 MSI-H / dMMR mCRC patients with an ECOG PS score of 0 or 1 were included in the study.
The median follow-up time of the pembrolizumab group was 44.
5 months (36.
0-60.
3), while the median follow-up time of the control group was 44.
5 months (36.
0-60.
3).
The follow-up time was 44.
4 months (36.
2-58.
6)
.
60% of patients in the control group received PD-1/PD-L1 immune checkpoint inhibitor treatment after disease progression; the median OS of the K drug group had not yet reached, and the median OS of the control group was 36.
7 months, and the risk of death Reduced by 26% (HR 0.
74; 95% CI, 0.
53-1.
03; P=0.
0359); the K drug treatment group showed a trend of OS benefit, the 36-month OS rate was 61%, and the control group was 50%
.
· The median PFS of the K drug group was 16.
5 months, which was twice that of the control chemotherapy group (8.
2 months) (HR=0.
59; 95%CI: 0.
45~0.
79; P=0.
0002); the K drug group was finally determined to be objective The response rate (ORR) was 45.
1% (20 CR, 49 PR), and the control group was 33.
1% (6 CR, 45 PR); the median duration of response (DOR) in the K drug group did not reach (2.
3+ ~ 53.
5+) , The control group was 10.
6 months (2.
8 ~ 48.
3+); the incidence of treatment-related adverse events (TRAE) above grade 3 in the K drug group was 21.
6%, and the control group was 66.
4%
.
For the first-line treatment of patients with MSI-H/dMMR mCRC, pembrolizumab has better PFS than conventional chemotherapy, the incidence of TRAE is lower, and there is a trend to reduce the risk of death, which may be due to the higher proportion of chemotherapy groups ( 60%) of patients crossed over from chemotherapy to anti-PD-1/PD-L1 treatment, resulting in OS that did not reach a statistical difference
.
In summary, pembrolizumab should still be used as the standard regimen for the first-line treatment of MSI-H/dMMR mCRC
.
RAS wild-type mCRC: The DEEPER (JACCROCC-13) study (Abs3501) The three-drug FOLFOXIRI regimen combined with bevacizumab or cetuximab for the treatment of RAS wild-type mCRC has been shown in the TRIBE and VOLFI studies to compare with the two-drug combination The program has better early tumor regression (ETS) and depth of regression (DpR)
.
A study from Japan at this ASCO annual meeting compared the efficacy and safety of bevacizumab versus cetuximab combined with FOLFOXIRI for RAS wild-type mCRC
.
A total of 359 subjects were enrolled in the study, including 173 in the cetuximab group and 175 in the bevacizumab group
.
The median treatment cycle of the cetuximab group was 10 (range: 1-51), and the median treatment cycle of the bevacizumab group was 12 (range: 1-51)
.
The study reached the primary endpoint: the DpR of the cetuximab group was 57.
4%, the DpR of the bevacizumab group was 46.
0% (p = 0.
0010); the median DpR of the primary tumor on the left was 60.
3% and 46.
1% (p = .
0007); the DpR of the primary tumor on the right side was 50.
0% vs.
41.
2% (p = 0.
46)
.
The ETS rate and ORR of the cetuximab group were 77.
8% and 69.
1%, and the ETS rate and ORR of the bevacizumab group were 74.
6% and 71.
7%, and the difference was not statistically significant
.
The PFS and OS of all populations were 12.
7 months (95% CI 11.
5-14.
0) and 37.
6 months (95% CI 30.
8-43.
0), respectively
.
Studies have shown that mFOLFOXIRI combined with cetuximab as the first-line treatment of RAS wild-type mCRC is significantly better than mFOLFOXIRI combined with bevacizumab in terms of DpR, which can bring deeper tumor regression for patients with left bowel cancer
.
BRAF V600E mutant metastatic colorectal cancer: FIRE-4.
5 study (Abs3502) FIRE-4.
5 (AIO KRK-0116) study compared FOLFOXIRI combined with cetuximab or bevacizumab in the treatment of patients with BRAF V600E mutant mCRC Curative effect
.
A total of 107 patients from 90 German and 10 French research centers were included in the study.
They were randomly assigned to receive FOLFOXIRI combined with Cetuximab (72 cases) or FOLFOXIRI combined with Bevacizumab (35 cases) at a 2:1 ratio.
.
No new or unexpected toxic reactions were observed in the study
.
In the intent-to-treat (ITT) population: the ORR of the cetuximab group was 40.
3%, and the ORR of the bevacizumab group was 51.
4% (p=0.
28), which did not reach the primary study endpoint
.
The median PFS in the bevacizumab group was significantly longer than that in the cetuximab group (8.
3 months vs 6.
0 months; p=0.
03; HR 1.
75)
.
The median OS was 16.
8 months in the bevacizumab group and 14.
6 months in the cetuximab group (p=0.
67; HR 1.
16), and the difference was not statistically significant
.
The results of the two groups of patients with the left semi-primary tumor were similar, while the bevacizumab group of patients with the right semi-primary tumor had a better therapeutic effect trend
.
FIRE-4.
5 is the first prospective randomized study to study the efficacy of FOLFOXIRI combined with targeted therapy in the first-line treatment of BRAF V600E mutant mCRC patients
.
FOLFOXIRI combined with bevacizumab or cetuximab has similar curative effects, but there are differences in curative effect according to the site of the primary tumor, which is related to the heterogeneity of the BRAF V600E mutation subgroup of mCRC patients
.
References: 1.
Final overall survival for the phase III KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).
ABSTRACT35002.
The randomized phase II study of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab as the first-line treatment in metastatic colorectal cancer with RAS wild-type tumors: The DEEPER trial (JACCRO CC-13).
ABSTRACT35013.
Randomized study to investigate FOLFOXIRI plus either bevacizumab or cetuximab as first-line treatment of BRAF V600E-mutant mCRC: The phase-II FIRE-4.
5 study (AIO KRK-0116).
ABSTRACT3502
