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The 2022 American Society of Clinical Oncology Symposium on Gastrointestinal Oncology (ASCO-GI) will be held from January 20 to 22 local time
.
Colorectal cancer (CRC) is the third most common malignancy in the world, and there are still many unsolved problems in its treatment
.
A number of research results at this ASCO-GI meeting are worth looking forward to
.
The editors of Yimaitong are as follows, for the convenience of readers
.
Immunotherapy may become a new choice for patients with microsatellite-stable BRAFV600E metastatic colorectal cancer came the short-term efficacy and survival benefits
.
BRAF combined with EGFR inhibitors induces a transient microsatellite hyperinstability (MSI-H) phenotype in a preclinical model of BRAFV600E CRC in MSS and may prompt these tumors to respond to anti-PD-inhibitors such as nivolumab (N).
1 antibody response to immunotherapy
.
Methods The study was a single-arm, single-center, phase I/II clinical trial
.
Inclusion criteria included BRAFV600E mCRC patients with refractory MSS who had not received prior BRAF inhibitors, anti-EGFR antibodies, or immunotherapy
.
After enrollment, patients received E (300 mg PO daily), C (500 mg/m2 IV every 14 days), and N (480 mg IV every 28 days)
.
The primary endpoints were best overall response rate (RECIST 1.
1) and safety/tolerability (CTCAE v5)
.
A Simon two-stage design with one-sided a=0.
05 and b=0.
20 was used (H0: p≤0.
22; Ha: p≥0.
45, where p=the percentage of patients with radiographic response)
.
In the first phase, a response of ≥4/15 patients was required for the trial to enroll an additional 11 patients
.
Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method
.
Results A total of 26 patients were enrolled, of which 23 received treatment and 21 were evaluable for efficacy
.
The median age was 59 years (32-85 years), and 14 patients (54%) were female
.
No dose-limiting toxicities occurred
.
Grade 3-4 treatment-related adverse reactions (AEs) occurred in 4/22 patients (18%)
.
Grade 3 AEs included colitis, maculopapular rash, leukocytosis, and elevated amylase/lipase (all n=1)
.
One patient had a grade 4 AE, myositis/myocarditis
.
The overall response rate was 45% (95% CI, 23-68), and the disease control rate was 95% (95% CI, 75-100)
.
The median PFS was 7.
3 months (95% CI, 5.
5-NA)
.
Median OS was 11.
4 months (95% CI, 7.
6-NA)
.
In 9 patients with a response to date, the median duration of response was 8.
1 months (95% CI, 7.
3-NA)
.
Conclusion E+C+N regimen is effective and well tolerated in the treatment of BRAFV600E mCRC patients with MSS
.
The E+C+N regimen achieved the pre-specified efficacy endpoint, indicating that immunotherapy, as a new combination therapy, can benefit in this specific subgroup of MSS mCRC
.
A follow-up randomized phase II trial (SWOG 2107) will be initiated in early 2022 to evaluate the efficacy of E/C with or without N in the treatment of BRAFV600E mCRC in MSS
.
GERCOR NIPICOL Phase II Study: Effect of Nivolumab in Combination with Ipilimumab or Background Immune Checkpoint Inhibitor (ICI) for MSI-H/Mismatch Repair Deficient ( The optimal duration of treatment for patients with dMMR) mCRC remains controversial
.
At present, the clinical duration is not uniform, mostly 2 years or until disease progression or intolerance of toxic reactions
.
Preliminary results from the GERCOR NIPICOL Phase II study in patients with MSI-H/dMMR mCRC treated with nivolumab plus ipilimumab for 1 year with 16-month follow-up are as follows
.
Methods MSI-H/dMMR mCRC patients treated with fluorouracil, oxaliplatin and irinotecan with or without targeted therapy received 4 cycles of nivolumab 3 mg/kg combined with ipilimumab 1 mg/kg Q3W Treatment, sequential nivolumab 3 mg/kg Q2W until disease progression or completion of up to 20 cycles of therapy
.
A second course of nivolumab was allowed for patients who completed the scheduled treatment year and developed disease progression (PD) later
.
The aim was to assess objective response rate (ORR), PFS and OS
.
PFS analysis was performed for patients who were alive and did not have disease progression after 1 year of treatment (theoretical end of treatment)
.
RESULTS: Between December 2017 and November 2018, a total of 57 patients were enrolled, of whom 36 (63%) completed the scheduled 1-year treatment
.
Reasons for early discontinuation were PD or death (n=13), adverse events (n=7), and patient preference (n=1)
.
The overall median follow-up was 34.
5 months
.
The 1-, 2-, and 3-year PFS rates were 75.
4% (95% CI 62.
0-84.
6), 70.
0% (95% CI 56.
2-80.
1), and 70.
0% (95% CI 56.
2-80.
1), respectively
.
The 1-, 2-, and 3-year OS rates were 84.
1% (95% CI 71.
7-91.
4), 78.
4% (95% CI 65.
1-87.
1), and 73.
1% (95% CI 58.
4-83.
4), respectively
.
Forty-two patients were disease-free and alive at 1 year, with a median follow-up of 35.
0 months, and the 24-month PFS rate was 92.
9% (95% CI 79.
5-97.
6%)
.
PD was observed in 3 patients with stable disease (SD) status at 12 months and received a second course of nivolumab, 2 patients had partial response (PR) and 1 had PD
.
Conclusion After 3 years of follow-up, nivolumab combined with ipilimumab for 1 year still showed long-term antitumor activity in chemotherapy-resistant MSI-H/dMMR mCRC patients
.
Sequential therapy with nivolumab may provide more antitumor activity in patients with advanced resistance after discontinuation of immunotherapy
.
A new option for refractory microsatellite stable colorectal cancer: regorafenib combined with pembrolizumab background ICI is suboptimal in MSS CRC
.
Combining ICIs with targeted drugs has the potential to alter the tumor microenvironment and make these tumors more susceptible to ICIs
.
The results of a multicenter study of regorafenib (rego) and pembrolizumab (pembro) in different advanced MSS CRC patients will be reported at this ASCO GI meeting
.
Methods This was an investigator-initiated study of patients with chemotherapy failure/intolerance at 3 centers
.
Phase I used a "3+3" study design to evaluate escalating doses of rego (80, 120, 160, days 1-14/21) in combination with pembro (200m, every 3 weeks)
.
The primary study endpoint was dose-limiting toxicity in the first cycle
.
In the phase II study, patients were treated with rego combined with pembro at the recommended phase II dose (RP2D)
.
The primary study endpoint was PFS
.
Secondary endpoints were OS and ORR
.
This study showed an improvement in PFS from 1.
9 months to 2.
85 months (CORRECT study data)
.
The estimated sample size for the second phase is 63 patients
.
The results study began in July 2019 and is expected to be completed in July 2021
.
Of the 73 patients, 10 participated in the first phase and 63 participated in the second phase
.
The RP2D dose of Rego was 80 mg (days 1-14/21), and 70 patients received this dose
.
As of September 14, 2021, 11 patients were still receiving treatment
.
The median age of enrolled patients was 54 years (23-81 years), 51% were female, 53% were white, 19% were Asian, 12% were black, and 11% were Hispanic, median number of prior lines of therapy 2 (1-5), 13% of primary lesions were located in the sigmoid colon and rectum, 68% had KRAS mutations, 5% had BRAF mutations, and 78% had liver metastases
.
There were no grade 4 treatment-related AEs
.
The most common grade 3 AE was rash (20%), followed by hand-foot syndrome and hypertension (7%)
.
Dose adjustment was required in 14% of patients
.
The most common reason for discontinuing treatment was disease progression (85%), followed by withdrawal of informed consent (12%)
.
The median follow-up time was 5.
3 months (0.
6-24.
4), the median PFS was 2.
0 months (1.
8-3.
5), and the median OS was 10.
9 months (5.
3-NR)
.
In 16 patients (23%) with non-hepatic metastatic disease, the PFS was 4.
3 months (1.
9-8.
4)
.
No objective remission events were observed
.
Stable disease was achieved in 49% of patients with a median duration of remission of 2 months (0.
2-18.
8)
.
Conclusion This study is currently the largest clinical study of ICI+rego combination therapy
.
Despite encouraging median OS, the trial did not meet its primary endpoint
.
Research to identify biomarkers in patients with long-term benefit is still ongoing
.
CheckMate 9X8 Phase II Study Results: Could the Addition of Nivolumab Provide Benefit for First-Line Treatment of Metastatic Colorectal Cancer? Standard first-line treatment regimens for background mCRC include fluorouracil in combination with oxaliplatin and/or irinotecan and biologics
.
In patients with mCRC, nivolumab (NIVO) in combination with first-line standard of care regimens may enhance antitumor activity
.
The CheckMate 9X8 study compared the efficacy and safety of NIVO in combination with mFOLFOX6 or bevacizumab (BEV) versus mFOLFOX6 or BEV in the first-line treatment of mCRC (NCT 03414983)
.
Methods Patients with previously untreated, initially unresectable mCRC were randomly assigned (2:1) to NIVO (240mg) + mFOLFOX6/BEV Q2W (NIVO + standard of care [SOC] group) or mFOLFOX6/BEV Q2W (SOC group)
.
The primary study endpoint was PFS as assessed by an independent blinded center (BICR) according to RECIST v1.
1
.
Secondary endpoints included ORR, disease control rate (DCR), time to response (TTR), duration of response (DOR), OS and safety
.
Results 195 patients were randomized into NIVO+SOC group (n=127) or SOC group (n=68)
.
The median follow-up time was 23.
7 months (0-33.
2) (NIVO+SOC group) and 23.
2 months (0-32.
3) (SOC group), and the median treatment duration was 9.
9 months (0.
1-31.
8+) and 9.
9 months, respectively.
7.
7 months (0.
1-26.
7+)
.
The HR for PFS was 0.
81 (95% CI 0.
53-1.
23; P=0.
30), which did not meet the prespecified threshold for statistical difference (median PFS was 11.
9 months in both groups)
.
The PFS rate after 12 months in the NIVO+SOC group was higher than that in the SOC group
.
The ORR was 60% (NIVO+SOC group) and 46% (SOC group; odds ratio 1.
72 [95% CI 0.
96-3.
10]), respectively, and the median DOR was 12.
9 months (95% CI 9.
0-13.
1) and 9.
3 months (95%CI 7.
5-11.
3)
.
Grade 3/4 treatment-related AEs were more frequent in the NIVO+SOC arm, but no new safety signals were identified
.
Biomarkers, including tumor mutational burden and baseline lymphocyte CD8 levels, will be further analyzed
.
Conclusion The primary endpoint of this study, PFS, was not reached
.
However, in the first-line treatment of mCRC, compared with the SOC group, the NIVO+SOC group showed higher PFS rate, higher objective response rate, longer duration of response and tolerable safety after 12 months
.
JCOG1018 study (RESPECT): Can the addition of oxaliplatin improve survival in elderly patients with metastatic colorectal cancer? Background: Whether fluorouracil plus bevacizumab (BEV) combined with oxaliplatin (OX) is suitable for the initial treatment of elderly patients with mCRC remains controversial
.
This study is a randomized controlled clinical trial to evaluate whether combined OX can improve PFS
.
The JCOG trial was originally planned as a parallel cell study of NCCTG, but the NCCTG trial was terminated early
.
Methods The main inclusion criteria included: unresectable mCRC, histologically confirmed adenocarcinoma, 70-74 years old with ECOG score of 2 or 75 years old with ECOG score of 0-2
.
Eligible patients were randomly assigned (1:1) to treatment with or without OX
.
Before the start of the study, determine whether to use fluorouracil + calcium levofolinate (5-FU/l-LV) or capecitabine (CAPE), including 5-FU/l-LV + BEV (group C), CAPE + BEV (Panel D), mFOLFOX7+BEV (Panel E) or CapeOX+BEV (Panel F)
.
The 5-FU/l-LV regimen omitted the intravenous bolus of 5-FU from the original sLV5FU regimen
.
Adjust CAPE dose based on creatinine clearance
.
The primary study endpoint was PFS
.
The planned sample size totaled 250 patients (HR 0.
75, one-sided α=5% and β=70%)
.
The study rule was that the primary study endpoint was met and the HR point estimate for OS was less than 0.
8
.
Results From September 2012 to March 2019, 251 enrolled patients were randomly assigned (1:1) to receive treatment with (n=126) or without (n=125) OX
.
The median age was 79 years old, and the age range of patients over 70-74, 75-79, 80-84, and 85 years old accounted for 5%, 45%, 37%, and 13%, respectively.
The ECOG score was 0, 1, and 2.
Patients accounted for 53%, 39%, and 7%, respectively
.
Of the 251 patients, 241 had PFS events and 223 had OS events
.
Median PFS was 9.
4 months (95% CI 8.
3-10.
3) in patients without OX and 10.
0 months (9.
0–11.
2) in patients with OX (HR 0.
837, 95% CI [0.
673–1.
042], one-sided p=0.
086)
.
Median OS was 21.
3 months (18.
7-24.
3) in patients without OX and 19.
7 months (15.
5-25.
5) in patients with OX (HR 1.
054 [0.
810-1.
372])
.
The effective rate was 29.
5% (21.
2-38.
8) in patients without OX and 47.
7% (38.
1-57.
5) in patients with OX
.
There was no difference in the proportion of patients whose EQ-5D score improved from baseline to post-treatment overall score (odds ratio 0.
94 [0.
51-1.
75])
.
One patient without OX and three patients with OX died were treatment-related
.
CONCLUSIONS: There was no survival benefit with OX compared to without OX
.
OX is not recommended as an initial treatment regimen for elderly patients with MCRC
.
References: 1.
Rapid Abstract Session and Poster Session 12.
Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer.
2.
Rapid Abstract Session and Poster Session 13.
One-year duration of nivolumab plus ipilimumab in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up of the GERCOR NIPICOL phase II study.
3.
Rapid Abstract Session and Poster Session 15.
Phase I/II study of regorafenib (rego) and pembrolizumab (pembro) in refractory microsatellite stable colorectal cancer (MSSCRC).
4.
Oral Abstract Session 8.
Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8.
5.
Oral Abstract Session 10.
A randomized phase III trial of mFOLFOX7 or CapeOX plus bevacizumab versus 5-FU/ l-LV or capecitabine plus bevacizumab as initial therapy in elderly patients with metastatic colorectal cancer: JCOG1018 study (RESPECT).
.
Colorectal cancer (CRC) is the third most common malignancy in the world, and there are still many unsolved problems in its treatment
.
A number of research results at this ASCO-GI meeting are worth looking forward to
.
The editors of Yimaitong are as follows, for the convenience of readers
.
Immunotherapy may become a new choice for patients with microsatellite-stable BRAFV600E metastatic colorectal cancer came the short-term efficacy and survival benefits
.
BRAF combined with EGFR inhibitors induces a transient microsatellite hyperinstability (MSI-H) phenotype in a preclinical model of BRAFV600E CRC in MSS and may prompt these tumors to respond to anti-PD-inhibitors such as nivolumab (N).
1 antibody response to immunotherapy
.
Methods The study was a single-arm, single-center, phase I/II clinical trial
.
Inclusion criteria included BRAFV600E mCRC patients with refractory MSS who had not received prior BRAF inhibitors, anti-EGFR antibodies, or immunotherapy
.
After enrollment, patients received E (300 mg PO daily), C (500 mg/m2 IV every 14 days), and N (480 mg IV every 28 days)
.
The primary endpoints were best overall response rate (RECIST 1.
1) and safety/tolerability (CTCAE v5)
.
A Simon two-stage design with one-sided a=0.
05 and b=0.
20 was used (H0: p≤0.
22; Ha: p≥0.
45, where p=the percentage of patients with radiographic response)
.
In the first phase, a response of ≥4/15 patients was required for the trial to enroll an additional 11 patients
.
Median progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method
.
Results A total of 26 patients were enrolled, of which 23 received treatment and 21 were evaluable for efficacy
.
The median age was 59 years (32-85 years), and 14 patients (54%) were female
.
No dose-limiting toxicities occurred
.
Grade 3-4 treatment-related adverse reactions (AEs) occurred in 4/22 patients (18%)
.
Grade 3 AEs included colitis, maculopapular rash, leukocytosis, and elevated amylase/lipase (all n=1)
.
One patient had a grade 4 AE, myositis/myocarditis
.
The overall response rate was 45% (95% CI, 23-68), and the disease control rate was 95% (95% CI, 75-100)
.
The median PFS was 7.
3 months (95% CI, 5.
5-NA)
.
Median OS was 11.
4 months (95% CI, 7.
6-NA)
.
In 9 patients with a response to date, the median duration of response was 8.
1 months (95% CI, 7.
3-NA)
.
Conclusion E+C+N regimen is effective and well tolerated in the treatment of BRAFV600E mCRC patients with MSS
.
The E+C+N regimen achieved the pre-specified efficacy endpoint, indicating that immunotherapy, as a new combination therapy, can benefit in this specific subgroup of MSS mCRC
.
A follow-up randomized phase II trial (SWOG 2107) will be initiated in early 2022 to evaluate the efficacy of E/C with or without N in the treatment of BRAFV600E mCRC in MSS
.
GERCOR NIPICOL Phase II Study: Effect of Nivolumab in Combination with Ipilimumab or Background Immune Checkpoint Inhibitor (ICI) for MSI-H/Mismatch Repair Deficient ( The optimal duration of treatment for patients with dMMR) mCRC remains controversial
.
At present, the clinical duration is not uniform, mostly 2 years or until disease progression or intolerance of toxic reactions
.
Preliminary results from the GERCOR NIPICOL Phase II study in patients with MSI-H/dMMR mCRC treated with nivolumab plus ipilimumab for 1 year with 16-month follow-up are as follows
.
Methods MSI-H/dMMR mCRC patients treated with fluorouracil, oxaliplatin and irinotecan with or without targeted therapy received 4 cycles of nivolumab 3 mg/kg combined with ipilimumab 1 mg/kg Q3W Treatment, sequential nivolumab 3 mg/kg Q2W until disease progression or completion of up to 20 cycles of therapy
.
A second course of nivolumab was allowed for patients who completed the scheduled treatment year and developed disease progression (PD) later
.
The aim was to assess objective response rate (ORR), PFS and OS
.
PFS analysis was performed for patients who were alive and did not have disease progression after 1 year of treatment (theoretical end of treatment)
.
RESULTS: Between December 2017 and November 2018, a total of 57 patients were enrolled, of whom 36 (63%) completed the scheduled 1-year treatment
.
Reasons for early discontinuation were PD or death (n=13), adverse events (n=7), and patient preference (n=1)
.
The overall median follow-up was 34.
5 months
.
The 1-, 2-, and 3-year PFS rates were 75.
4% (95% CI 62.
0-84.
6), 70.
0% (95% CI 56.
2-80.
1), and 70.
0% (95% CI 56.
2-80.
1), respectively
.
The 1-, 2-, and 3-year OS rates were 84.
1% (95% CI 71.
7-91.
4), 78.
4% (95% CI 65.
1-87.
1), and 73.
1% (95% CI 58.
4-83.
4), respectively
.
Forty-two patients were disease-free and alive at 1 year, with a median follow-up of 35.
0 months, and the 24-month PFS rate was 92.
9% (95% CI 79.
5-97.
6%)
.
PD was observed in 3 patients with stable disease (SD) status at 12 months and received a second course of nivolumab, 2 patients had partial response (PR) and 1 had PD
.
Conclusion After 3 years of follow-up, nivolumab combined with ipilimumab for 1 year still showed long-term antitumor activity in chemotherapy-resistant MSI-H/dMMR mCRC patients
.
Sequential therapy with nivolumab may provide more antitumor activity in patients with advanced resistance after discontinuation of immunotherapy
.
A new option for refractory microsatellite stable colorectal cancer: regorafenib combined with pembrolizumab background ICI is suboptimal in MSS CRC
.
Combining ICIs with targeted drugs has the potential to alter the tumor microenvironment and make these tumors more susceptible to ICIs
.
The results of a multicenter study of regorafenib (rego) and pembrolizumab (pembro) in different advanced MSS CRC patients will be reported at this ASCO GI meeting
.
Methods This was an investigator-initiated study of patients with chemotherapy failure/intolerance at 3 centers
.
Phase I used a "3+3" study design to evaluate escalating doses of rego (80, 120, 160, days 1-14/21) in combination with pembro (200m, every 3 weeks)
.
The primary study endpoint was dose-limiting toxicity in the first cycle
.
In the phase II study, patients were treated with rego combined with pembro at the recommended phase II dose (RP2D)
.
The primary study endpoint was PFS
.
Secondary endpoints were OS and ORR
.
This study showed an improvement in PFS from 1.
9 months to 2.
85 months (CORRECT study data)
.
The estimated sample size for the second phase is 63 patients
.
The results study began in July 2019 and is expected to be completed in July 2021
.
Of the 73 patients, 10 participated in the first phase and 63 participated in the second phase
.
The RP2D dose of Rego was 80 mg (days 1-14/21), and 70 patients received this dose
.
As of September 14, 2021, 11 patients were still receiving treatment
.
The median age of enrolled patients was 54 years (23-81 years), 51% were female, 53% were white, 19% were Asian, 12% were black, and 11% were Hispanic, median number of prior lines of therapy 2 (1-5), 13% of primary lesions were located in the sigmoid colon and rectum, 68% had KRAS mutations, 5% had BRAF mutations, and 78% had liver metastases
.
There were no grade 4 treatment-related AEs
.
The most common grade 3 AE was rash (20%), followed by hand-foot syndrome and hypertension (7%)
.
Dose adjustment was required in 14% of patients
.
The most common reason for discontinuing treatment was disease progression (85%), followed by withdrawal of informed consent (12%)
.
The median follow-up time was 5.
3 months (0.
6-24.
4), the median PFS was 2.
0 months (1.
8-3.
5), and the median OS was 10.
9 months (5.
3-NR)
.
In 16 patients (23%) with non-hepatic metastatic disease, the PFS was 4.
3 months (1.
9-8.
4)
.
No objective remission events were observed
.
Stable disease was achieved in 49% of patients with a median duration of remission of 2 months (0.
2-18.
8)
.
Conclusion This study is currently the largest clinical study of ICI+rego combination therapy
.
Despite encouraging median OS, the trial did not meet its primary endpoint
.
Research to identify biomarkers in patients with long-term benefit is still ongoing
.
CheckMate 9X8 Phase II Study Results: Could the Addition of Nivolumab Provide Benefit for First-Line Treatment of Metastatic Colorectal Cancer? Standard first-line treatment regimens for background mCRC include fluorouracil in combination with oxaliplatin and/or irinotecan and biologics
.
In patients with mCRC, nivolumab (NIVO) in combination with first-line standard of care regimens may enhance antitumor activity
.
The CheckMate 9X8 study compared the efficacy and safety of NIVO in combination with mFOLFOX6 or bevacizumab (BEV) versus mFOLFOX6 or BEV in the first-line treatment of mCRC (NCT 03414983)
.
Methods Patients with previously untreated, initially unresectable mCRC were randomly assigned (2:1) to NIVO (240mg) + mFOLFOX6/BEV Q2W (NIVO + standard of care [SOC] group) or mFOLFOX6/BEV Q2W (SOC group)
.
The primary study endpoint was PFS as assessed by an independent blinded center (BICR) according to RECIST v1.
1
.
Secondary endpoints included ORR, disease control rate (DCR), time to response (TTR), duration of response (DOR), OS and safety
.
Results 195 patients were randomized into NIVO+SOC group (n=127) or SOC group (n=68)
.
The median follow-up time was 23.
7 months (0-33.
2) (NIVO+SOC group) and 23.
2 months (0-32.
3) (SOC group), and the median treatment duration was 9.
9 months (0.
1-31.
8+) and 9.
9 months, respectively.
7.
7 months (0.
1-26.
7+)
.
The HR for PFS was 0.
81 (95% CI 0.
53-1.
23; P=0.
30), which did not meet the prespecified threshold for statistical difference (median PFS was 11.
9 months in both groups)
.
The PFS rate after 12 months in the NIVO+SOC group was higher than that in the SOC group
.
The ORR was 60% (NIVO+SOC group) and 46% (SOC group; odds ratio 1.
72 [95% CI 0.
96-3.
10]), respectively, and the median DOR was 12.
9 months (95% CI 9.
0-13.
1) and 9.
3 months (95%CI 7.
5-11.
3)
.
Grade 3/4 treatment-related AEs were more frequent in the NIVO+SOC arm, but no new safety signals were identified
.
Biomarkers, including tumor mutational burden and baseline lymphocyte CD8 levels, will be further analyzed
.
Conclusion The primary endpoint of this study, PFS, was not reached
.
However, in the first-line treatment of mCRC, compared with the SOC group, the NIVO+SOC group showed higher PFS rate, higher objective response rate, longer duration of response and tolerable safety after 12 months
.
JCOG1018 study (RESPECT): Can the addition of oxaliplatin improve survival in elderly patients with metastatic colorectal cancer? Background: Whether fluorouracil plus bevacizumab (BEV) combined with oxaliplatin (OX) is suitable for the initial treatment of elderly patients with mCRC remains controversial
.
This study is a randomized controlled clinical trial to evaluate whether combined OX can improve PFS
.
The JCOG trial was originally planned as a parallel cell study of NCCTG, but the NCCTG trial was terminated early
.
Methods The main inclusion criteria included: unresectable mCRC, histologically confirmed adenocarcinoma, 70-74 years old with ECOG score of 2 or 75 years old with ECOG score of 0-2
.
Eligible patients were randomly assigned (1:1) to treatment with or without OX
.
Before the start of the study, determine whether to use fluorouracil + calcium levofolinate (5-FU/l-LV) or capecitabine (CAPE), including 5-FU/l-LV + BEV (group C), CAPE + BEV (Panel D), mFOLFOX7+BEV (Panel E) or CapeOX+BEV (Panel F)
.
The 5-FU/l-LV regimen omitted the intravenous bolus of 5-FU from the original sLV5FU regimen
.
Adjust CAPE dose based on creatinine clearance
.
The primary study endpoint was PFS
.
The planned sample size totaled 250 patients (HR 0.
75, one-sided α=5% and β=70%)
.
The study rule was that the primary study endpoint was met and the HR point estimate for OS was less than 0.
8
.
Results From September 2012 to March 2019, 251 enrolled patients were randomly assigned (1:1) to receive treatment with (n=126) or without (n=125) OX
.
The median age was 79 years old, and the age range of patients over 70-74, 75-79, 80-84, and 85 years old accounted for 5%, 45%, 37%, and 13%, respectively.
The ECOG score was 0, 1, and 2.
Patients accounted for 53%, 39%, and 7%, respectively
.
Of the 251 patients, 241 had PFS events and 223 had OS events
.
Median PFS was 9.
4 months (95% CI 8.
3-10.
3) in patients without OX and 10.
0 months (9.
0–11.
2) in patients with OX (HR 0.
837, 95% CI [0.
673–1.
042], one-sided p=0.
086)
.
Median OS was 21.
3 months (18.
7-24.
3) in patients without OX and 19.
7 months (15.
5-25.
5) in patients with OX (HR 1.
054 [0.
810-1.
372])
.
The effective rate was 29.
5% (21.
2-38.
8) in patients without OX and 47.
7% (38.
1-57.
5) in patients with OX
.
There was no difference in the proportion of patients whose EQ-5D score improved from baseline to post-treatment overall score (odds ratio 0.
94 [0.
51-1.
75])
.
One patient without OX and three patients with OX died were treatment-related
.
CONCLUSIONS: There was no survival benefit with OX compared to without OX
.
OX is not recommended as an initial treatment regimen for elderly patients with MCRC
.
References: 1.
Rapid Abstract Session and Poster Session 12.
Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer.
2.
Rapid Abstract Session and Poster Session 13.
One-year duration of nivolumab plus ipilimumab in patients (pts) with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR) metastatic colorectal cancer (mCRC): Long-term follow-up of the GERCOR NIPICOL phase II study.
3.
Rapid Abstract Session and Poster Session 15.
Phase I/II study of regorafenib (rego) and pembrolizumab (pembro) in refractory microsatellite stable colorectal cancer (MSSCRC).
4.
Oral Abstract Session 8.
Nivolumab (NIVO) + 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6)/bevacizumab (BEV) versus mFOLFOX6/BEV for first-line (1L) treatment of metastatic colorectal cancer (mCRC): Phase 2 results from CheckMate 9X8.
5.
Oral Abstract Session 10.
A randomized phase III trial of mFOLFOX7 or CapeOX plus bevacizumab versus 5-FU/ l-LV or capecitabine plus bevacizumab as initial therapy in elderly patients with metastatic colorectal cancer: JCOG1018 study (RESPECT).
