TY - JOUR
T1 - Prognostic impact of performance status on the outcomes of immune checkpoint inhibition strategies in patients with dMMR/MSI-H metastatic colorectal cancer
AU - Mazzoli, Giacomo
AU - Cohen, Romain
AU - Lonardi, Sara
AU - Corti, Francesca
AU - Elez, Elena
AU - Fakih, Marwan
AU - Jayachandran, Priya
AU - Colle, Raphael
AU - Shah, Aakash Tushar
AU - Salati, Massimiliano
AU - Fenocchio, Elisabetta
AU - Salvatore, Lisa
AU - Ambrosini, Margherita
AU - Ros, Javier
AU - Intini, Rossana
AU - Cremolini, Chiara
AU - Overman, Michael J.
AU - André, Thierry
AU - Pietrantonio, Filippo
N1 - Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/9
Y1 - 2022/9
N2 - Background: Immune checkpoint inhibitors yielded unprecedented outcomes in patients with mismatch repair deficient/ microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC), but clinical decision-making in this rapidly evolving treatment landscape is challenging. Since performance status (PS) represents a well-established prognostic factor in clinical practice, we investigated whether worse PS, overall or related to either patients' frailty or high tumour burden, could affect the outcomes in this whole patients’ population and according to immune checkpoint inhibitor treatment type. Methods: We conducted a global study at Tertiary Cancer Centres and collected data of patients with dMMR/MSI-H mCRC treated with anti- programmed-death (ligand)-1 (PD(L)-1) monotherapy or anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination. Results: The cohort included 502 patients. At a median follow-up of 31.2 months, worse PFS and OS were reported in patients with patient-related PS ≥ 1 (adjusted-HRs: 1.73, 95%CI: 1.06–2.83, p = 0.004 and 2.06, 95%CI: 1.13–3.74, p = 0.001, respectively) and cancer-related PS ≥ 1 (adjusted-HRs: 1.61, 95%CI: 1.19–2.17, p = 0.004 and 1.87, 95%CI: 1.32–2.66, p = 0.001, respectively). Anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination did not provide significantly better survival compared to anti-PD(L)-1 monotherapy in PS 0 subgroup (PFS HR = 0.62, 95%CI: 0.37–1.02, p = 0.059; OS HR = 0.59, 95%CI: 0.32–1.11, p = 0.100) and in patient-related PS ≥ 1 (PFS HR 0.93, 95%CI: 0.31–2.83, p = 0.899; OS HR 1.22, 95%CI: 0.34–4.37, p = 0.760), but the difference was significant and clinically meaningful in the subgroup with cancer-related PS ≥ 1 (PFS HR = 0.32, 95%CI: 0.19–0.53, p < 0.001; OS HR = 0.26, 95%CI: 0.14–0.48, p < 0.001). Conclusions: In patients with dMMR/MSI-H mCRC, an extensive evaluation of clinical variables including PS may be implemented in the therapy decision-making.
AB - Background: Immune checkpoint inhibitors yielded unprecedented outcomes in patients with mismatch repair deficient/ microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC), but clinical decision-making in this rapidly evolving treatment landscape is challenging. Since performance status (PS) represents a well-established prognostic factor in clinical practice, we investigated whether worse PS, overall or related to either patients' frailty or high tumour burden, could affect the outcomes in this whole patients’ population and according to immune checkpoint inhibitor treatment type. Methods: We conducted a global study at Tertiary Cancer Centres and collected data of patients with dMMR/MSI-H mCRC treated with anti- programmed-death (ligand)-1 (PD(L)-1) monotherapy or anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination. Results: The cohort included 502 patients. At a median follow-up of 31.2 months, worse PFS and OS were reported in patients with patient-related PS ≥ 1 (adjusted-HRs: 1.73, 95%CI: 1.06–2.83, p = 0.004 and 2.06, 95%CI: 1.13–3.74, p = 0.001, respectively) and cancer-related PS ≥ 1 (adjusted-HRs: 1.61, 95%CI: 1.19–2.17, p = 0.004 and 1.87, 95%CI: 1.32–2.66, p = 0.001, respectively). Anti-PD-1/anti- cytotoxic T-lymphocyte antigen 4 combination did not provide significantly better survival compared to anti-PD(L)-1 monotherapy in PS 0 subgroup (PFS HR = 0.62, 95%CI: 0.37–1.02, p = 0.059; OS HR = 0.59, 95%CI: 0.32–1.11, p = 0.100) and in patient-related PS ≥ 1 (PFS HR 0.93, 95%CI: 0.31–2.83, p = 0.899; OS HR 1.22, 95%CI: 0.34–4.37, p = 0.760), but the difference was significant and clinically meaningful in the subgroup with cancer-related PS ≥ 1 (PFS HR = 0.32, 95%CI: 0.19–0.53, p < 0.001; OS HR = 0.26, 95%CI: 0.14–0.48, p < 0.001). Conclusions: In patients with dMMR/MSI-H mCRC, an extensive evaluation of clinical variables including PS may be implemented in the therapy decision-making.
KW - Colorectal cancer
KW - Immunotherapy
KW - Microsatellite instability
KW - Performance status
KW - Prognosis
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U2 - 10.1016/j.ejca.2022.05.044
DO - 10.1016/j.ejca.2022.05.044
M3 - Article
C2 - 35777274
AN - SCOPUS:85132936326
SN - 0959-8049
VL - 172
SP - 171
EP - 181
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -