User login
Adding oxaliplatin to fluoropyrimidine improves survival outcomes in patients with stage 3 N1 colon cancer whose tumors show microsatellite instability (MSI), according to a pooled analysis of individual patient data from 12 adjuvant trials.
The findings suggest the treatment combination should be the standard of care adjuvant treatment in this setting, and that N stage “should at least be a stratification parameter” in future trials in the MSI population, the investigators said.
Overall survival (OS) in 185 patients with MSI, which is associated with a deficient DNA mismatch repair system (dMMR), and 1,440 patients with microsatellite stability (MSS), which is associated with a proficient mismatch repair (pMMR), was better with the combination therapy versus fluoropyrimidine alone (adjusted hazard ratios, 0.52 and 0.89 for the groups, respectively), Romain Cohen, MD, PhD, of Saint-Antoine Hospital, medical oncology department, Sorbonne Universite, both in Paris, and colleagues reported online in the Journal of Clinical Oncology.
Encouraging results
Disease-free survival (DFS) was similarly improved with the combination therapy in the MSI and MSS groups (aHRs, 0.47 and 0.82, respectively).
Further, in 461 MSI/dMMR and 3,789 MSS/pMMR patients treated with the combination therapy, MSI status had different prognostic effects depending on N stage category.
“Compared with MSS/pMMR, MSI/dMMR was associated with better OS in the N1 population (HR, 0.66) but a similar OS in the N2 population (HR, 1.13),” they wrote.
Multivariate analysis showed that prognosticators for OS were N stage (HR for OS in N2 vs. N1, 3.10), T stage (HR for OS with T4 vs. T1-3, 2.39), and sex (HR for OS in men vs. women, HR, 1.71).
The 3-year DFS estimates for N2 vs. N1 disease in the MSI/dMMR group were 65% versus 87%, for T4 versus T1-3 they were 60.4% versus 82.1%, and for high- versus low-risk MSI/dMMR colorectal cancer patients they were 64.5% versus 90.1%.
“MSI/dMMR has become a major theranostic biomarker, harboring a high discrimination capacity for the efficacy of immune checkpoint inhibitors among patients with colorectal cancer,” the authors noted. “Given their impressive activity in the metastatic setting, this justifies evaluating these antibodies in the adjuvant setting.”
To date, the efficacy of the adding oxaliplatin to fluoropyrimidine inpatients with stage 3 colon cancer and MSI has not been clearly demonstrated, they added.
Therefore, they analyzed individual patient data from 12 randomized, controlled, phase 3 trials in the ACCENT database and adjusted for demographic and clinicopathologic factors.
“Here, in the T4 and/or N2 MSI/dMMR groups, we were able to identify populations of patients with MSI/dMMR [stage 3 colorectal cancer] with a high risk of disease recurrence. Indeed, the estimated 3-year DFS rates of patients with MSI/dMMR T4 stage III and N2 patients were, respectively, 60.4% and 64.9%, the latter experiencing poorer survival than the MSS/pMMR N2 population,” they wrote, concluding that, “with one-third of T4 and/or N2 high-risk ... patients experiencing disease recurrence or death within 2 years after curative tumor resection, therapeutic innovations should be sought for this patient population.”
This study was supported by the National Cancer Institute, the ARCAD foundation, and research grants from Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. Dr. Cohen reported research funding and/or honoraria from Servier and MSD Oncology.
Adding oxaliplatin to fluoropyrimidine improves survival outcomes in patients with stage 3 N1 colon cancer whose tumors show microsatellite instability (MSI), according to a pooled analysis of individual patient data from 12 adjuvant trials.
The findings suggest the treatment combination should be the standard of care adjuvant treatment in this setting, and that N stage “should at least be a stratification parameter” in future trials in the MSI population, the investigators said.
Overall survival (OS) in 185 patients with MSI, which is associated with a deficient DNA mismatch repair system (dMMR), and 1,440 patients with microsatellite stability (MSS), which is associated with a proficient mismatch repair (pMMR), was better with the combination therapy versus fluoropyrimidine alone (adjusted hazard ratios, 0.52 and 0.89 for the groups, respectively), Romain Cohen, MD, PhD, of Saint-Antoine Hospital, medical oncology department, Sorbonne Universite, both in Paris, and colleagues reported online in the Journal of Clinical Oncology.
Encouraging results
Disease-free survival (DFS) was similarly improved with the combination therapy in the MSI and MSS groups (aHRs, 0.47 and 0.82, respectively).
Further, in 461 MSI/dMMR and 3,789 MSS/pMMR patients treated with the combination therapy, MSI status had different prognostic effects depending on N stage category.
“Compared with MSS/pMMR, MSI/dMMR was associated with better OS in the N1 population (HR, 0.66) but a similar OS in the N2 population (HR, 1.13),” they wrote.
Multivariate analysis showed that prognosticators for OS were N stage (HR for OS in N2 vs. N1, 3.10), T stage (HR for OS with T4 vs. T1-3, 2.39), and sex (HR for OS in men vs. women, HR, 1.71).
The 3-year DFS estimates for N2 vs. N1 disease in the MSI/dMMR group were 65% versus 87%, for T4 versus T1-3 they were 60.4% versus 82.1%, and for high- versus low-risk MSI/dMMR colorectal cancer patients they were 64.5% versus 90.1%.
“MSI/dMMR has become a major theranostic biomarker, harboring a high discrimination capacity for the efficacy of immune checkpoint inhibitors among patients with colorectal cancer,” the authors noted. “Given their impressive activity in the metastatic setting, this justifies evaluating these antibodies in the adjuvant setting.”
To date, the efficacy of the adding oxaliplatin to fluoropyrimidine inpatients with stage 3 colon cancer and MSI has not been clearly demonstrated, they added.
Therefore, they analyzed individual patient data from 12 randomized, controlled, phase 3 trials in the ACCENT database and adjusted for demographic and clinicopathologic factors.
“Here, in the T4 and/or N2 MSI/dMMR groups, we were able to identify populations of patients with MSI/dMMR [stage 3 colorectal cancer] with a high risk of disease recurrence. Indeed, the estimated 3-year DFS rates of patients with MSI/dMMR T4 stage III and N2 patients were, respectively, 60.4% and 64.9%, the latter experiencing poorer survival than the MSS/pMMR N2 population,” they wrote, concluding that, “with one-third of T4 and/or N2 high-risk ... patients experiencing disease recurrence or death within 2 years after curative tumor resection, therapeutic innovations should be sought for this patient population.”
This study was supported by the National Cancer Institute, the ARCAD foundation, and research grants from Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. Dr. Cohen reported research funding and/or honoraria from Servier and MSD Oncology.
Adding oxaliplatin to fluoropyrimidine improves survival outcomes in patients with stage 3 N1 colon cancer whose tumors show microsatellite instability (MSI), according to a pooled analysis of individual patient data from 12 adjuvant trials.
The findings suggest the treatment combination should be the standard of care adjuvant treatment in this setting, and that N stage “should at least be a stratification parameter” in future trials in the MSI population, the investigators said.
Overall survival (OS) in 185 patients with MSI, which is associated with a deficient DNA mismatch repair system (dMMR), and 1,440 patients with microsatellite stability (MSS), which is associated with a proficient mismatch repair (pMMR), was better with the combination therapy versus fluoropyrimidine alone (adjusted hazard ratios, 0.52 and 0.89 for the groups, respectively), Romain Cohen, MD, PhD, of Saint-Antoine Hospital, medical oncology department, Sorbonne Universite, both in Paris, and colleagues reported online in the Journal of Clinical Oncology.
Encouraging results
Disease-free survival (DFS) was similarly improved with the combination therapy in the MSI and MSS groups (aHRs, 0.47 and 0.82, respectively).
Further, in 461 MSI/dMMR and 3,789 MSS/pMMR patients treated with the combination therapy, MSI status had different prognostic effects depending on N stage category.
“Compared with MSS/pMMR, MSI/dMMR was associated with better OS in the N1 population (HR, 0.66) but a similar OS in the N2 population (HR, 1.13),” they wrote.
Multivariate analysis showed that prognosticators for OS were N stage (HR for OS in N2 vs. N1, 3.10), T stage (HR for OS with T4 vs. T1-3, 2.39), and sex (HR for OS in men vs. women, HR, 1.71).
The 3-year DFS estimates for N2 vs. N1 disease in the MSI/dMMR group were 65% versus 87%, for T4 versus T1-3 they were 60.4% versus 82.1%, and for high- versus low-risk MSI/dMMR colorectal cancer patients they were 64.5% versus 90.1%.
“MSI/dMMR has become a major theranostic biomarker, harboring a high discrimination capacity for the efficacy of immune checkpoint inhibitors among patients with colorectal cancer,” the authors noted. “Given their impressive activity in the metastatic setting, this justifies evaluating these antibodies in the adjuvant setting.”
To date, the efficacy of the adding oxaliplatin to fluoropyrimidine inpatients with stage 3 colon cancer and MSI has not been clearly demonstrated, they added.
Therefore, they analyzed individual patient data from 12 randomized, controlled, phase 3 trials in the ACCENT database and adjusted for demographic and clinicopathologic factors.
“Here, in the T4 and/or N2 MSI/dMMR groups, we were able to identify populations of patients with MSI/dMMR [stage 3 colorectal cancer] with a high risk of disease recurrence. Indeed, the estimated 3-year DFS rates of patients with MSI/dMMR T4 stage III and N2 patients were, respectively, 60.4% and 64.9%, the latter experiencing poorer survival than the MSS/pMMR N2 population,” they wrote, concluding that, “with one-third of T4 and/or N2 high-risk ... patients experiencing disease recurrence or death within 2 years after curative tumor resection, therapeutic innovations should be sought for this patient population.”
This study was supported by the National Cancer Institute, the ARCAD foundation, and research grants from Nuovo-Soldati Foundation, ARC Foundation for Cancer Research, and Servier Institute. Dr. Cohen reported research funding and/or honoraria from Servier and MSD Oncology.
FROM THE JOURNAL OF CLINICAL ONCOLOGY