RT Journal Article SR Electronic T1 Nomogram to predict the outcomes of patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP e003370 DO 10.1136/jitc-2021-003370 VO 9 IS 8 A1 Filippo Pietrantonio A1 Sara Lonardi A1 Francesca Corti A1 Gabriele Infante A1 Maria Elena Elez A1 Marwan Fakih A1 Priya Jayachandran A1 Aakash Tushar Shah A1 Massimiliano Salati A1 Elisabetta Fenocchio A1 Lisa Salvatore A1 Giuseppe Curigliano A1 Chiara Cremolini A1 Margherita Ambrosini A1 Javier Ros A1 Rossana Intini A1 Floriana Nappo A1 Silvia Damian A1 Federica Morano A1 Giovanni Fucà A1 Michael Overman A1 Rosalba Miceli YR 2021 UL http://jitc.bmj.com/content/9/8/e003370.abstract AB Background The efficacy of immune checkpoint inhibitors (ICIs) in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC) is unprecedented. A relevant proportion of subjects achieving durable disease control may be considered potentially ‘cured’, as opposed to patients experiencing primary ICI refractoriness or short-term clinical benefit. We developed and externally validated a nomogram to estimate the progression-free survival (PFS) and the time-independent event-free probability (EFP) in patients with MSI-high mCRC receiving ICIs.Methods The PFS and EFP were estimated using a cure model fitted on a developing set of 163 patients and validated on a set of 146 patients with MSI-high mCRC receiving anti-programmed death (ligand)1 (PD-(L)1) ± anticytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. A total of 23 putative prognostic factors were chosen and then selected using a random survival forest (RSF). The model performance in estimating PFS probability was evaluated by assessing calibration (internally—developing set and externally—validating set) and quantifying the discriminative ability (Harrell C index).Results RFS selected five variables: ICI type (anti-PD-(L)1 monotherapy vs anti-CTLA-4 combo), ECOG PS (0 vs >0), neutrophil-to-lymphocyte ratio (≤3 vs >3), platelet count, and prior treatment lines. As both in the developing and validation series most PFS events occurred within 12 months, this was chosen as cut-point for PFS prediction. The combination of the selected variables allowed estimation of the 12-month PFS (focused on patients with low chance of being cured) and the EFP (focused on patients likely to be event-free at a certain point of their follow-up). ICI type was significantly associated with disease control, as patients receiving the anti-CTLA-4-combination experienced the best outcomes. The calibration of PFS predictions was good both in the developing and validating sets. The median value of the EFP (46%) allowed segregation of two prognostic groups in both the developing (PFS HR=3.73, 95% CI 2.25 to 6.18; p<0.0001) and validating (PFS HR=1.86, 95% CI 1.07 to 3.23; p=0.0269) sets.Conclusions A nomogram based on five easily assessable variables including ICI treatment was built to estimate the outcomes of patients with MSI-high mCRC, with the potential to assist clinicians in their clinical practice. The web-based system ‘MSI mCRC Cure’ was released.Data are available upon reasonable request.