TY - JOUR
T1 - Efficacy of immune checkpoint inhibitors for metastatic colorectal cancer with microsatellite instability in second or latter line using synthetic control arms
T2 - A non-randomised evaluation
AU - Cohen, Romain
AU - Raeisi, Morteza
AU - Chibaudel, Benoist
AU - Yoshino, Takayuki
AU - Shi, Qian
AU - Zalcberg, John R.
AU - Adams, Richard
AU - Cremolini, Chiara
AU - Grothey, Axel
AU - Mayer, Robert J.
AU - Van Cutsem, Eric
AU - Tabernero, Josep
AU - Bando, Hideaki
AU - Misumi, Toshihiro
AU - Overman, Michael J.
AU - André, Thierry
AU - de Gramont, Aimery
N1 - Publisher Copyright:
© 2024 Elsevier Ltd
PY - 2024/3
Y1 - 2024/3
N2 - Purpose: Immune checkpoint inhibitors (ICIs) appeared active in single-arm trials for patients with chemoresistant metastatic colorectal cancer (mCRC) harboring microsatellite instability (MSI). Given the paucity of randomised controlled trials (RCTs) in this setting, we evaluated the effect size of ICIs using intra-patients comparison and ARCAD database as historical controls. Patients and methods: Individual-patient data from NIPICOL and CheckMate 142 phase II trials that evaluated a combination of ICIs for MSI mCRC patients (N = 176) and from five non-ICI mCRC historical RCTs in second-line or latter (N = 4026) were analyzed. Firstly, promising of ICIs was identified using intra-patient comparison based on growth modulation index (GMI) defined the ratio of progression-free survivals (PFS) on ICIs and previous line of therapy. Survival outcomes of ICIs-treated patients were then compared with those matched non-ICIs treated from ARCAD database historical RCTs. Results: Among ICIs-treated patients, median PFS on ICIs was 32.66 (range 0.10–74.25) versus 4.07 months (range 0.7–49.87) on prior therapy, resulting on median GMI of 4.97 (range 0.07–59.51; hazard-ratio (HR)= 0.16 (95 %CI=0.11–0.22, P < 0.001)). Compared to matched non-ICI patients, in third-line, median overall survival (OS) was not reached with ICIs versus 3.52 months with placebo (HR=0.20, 95 %CI=0.10–0.41, P < 0.001), and 6.51 months with active drugs (HR=0.30, 95 %CI=0.15–0.60, P = 0.001). In second-line, median OS was not reached with ICIs versus 11.7 months with chemotherapy+placebo (HR=0.12, 95 %CI=0.07–0.22, P < 0.001), and 16.3 months with chemotherapy+targeted therapy (HR=0.10, 95 %CI=0.05–0.19, P < 0.001). Conclusion: ICIs demonstrates high effect size for MSI mCRC patients in second-line and later. This work might be useful as an example of methodology to avoid RCTs when benefit from experimental therapy is likely to be high.
AB - Purpose: Immune checkpoint inhibitors (ICIs) appeared active in single-arm trials for patients with chemoresistant metastatic colorectal cancer (mCRC) harboring microsatellite instability (MSI). Given the paucity of randomised controlled trials (RCTs) in this setting, we evaluated the effect size of ICIs using intra-patients comparison and ARCAD database as historical controls. Patients and methods: Individual-patient data from NIPICOL and CheckMate 142 phase II trials that evaluated a combination of ICIs for MSI mCRC patients (N = 176) and from five non-ICI mCRC historical RCTs in second-line or latter (N = 4026) were analyzed. Firstly, promising of ICIs was identified using intra-patient comparison based on growth modulation index (GMI) defined the ratio of progression-free survivals (PFS) on ICIs and previous line of therapy. Survival outcomes of ICIs-treated patients were then compared with those matched non-ICIs treated from ARCAD database historical RCTs. Results: Among ICIs-treated patients, median PFS on ICIs was 32.66 (range 0.10–74.25) versus 4.07 months (range 0.7–49.87) on prior therapy, resulting on median GMI of 4.97 (range 0.07–59.51; hazard-ratio (HR)= 0.16 (95 %CI=0.11–0.22, P < 0.001)). Compared to matched non-ICI patients, in third-line, median overall survival (OS) was not reached with ICIs versus 3.52 months with placebo (HR=0.20, 95 %CI=0.10–0.41, P < 0.001), and 6.51 months with active drugs (HR=0.30, 95 %CI=0.15–0.60, P = 0.001). In second-line, median OS was not reached with ICIs versus 11.7 months with chemotherapy+placebo (HR=0.12, 95 %CI=0.07–0.22, P < 0.001), and 16.3 months with chemotherapy+targeted therapy (HR=0.10, 95 %CI=0.05–0.19, P < 0.001). Conclusion: ICIs demonstrates high effect size for MSI mCRC patients in second-line and later. This work might be useful as an example of methodology to avoid RCTs when benefit from experimental therapy is likely to be high.
KW - Immune checkpoint inhibitors
KW - Matching
KW - Microsatellite instability metastatic colorectal cancer
KW - Placebo
KW - Synthetic control arms
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U2 - 10.1016/j.ejca.2024.113537
DO - 10.1016/j.ejca.2024.113537
M3 - Article
C2 - 38241818
AN - SCOPUS:85182877264
SN - 0959-8049
VL - 199
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 113537
ER -