TY - JOUR
T1 - Association of the prognostic model iSEND with PD-1/L1 monotherapy outcome in non-small-cell lung cancer
AU - Park, Wungki
AU - Mezquita, Laura
AU - Okabe, Naoyuki
AU - Chae, Young Kwang
AU - Kwon, Deukwoo
AU - Saravia, Diana
AU - Auclin, Edouard
AU - Planchard, David
AU - Caramella, Caroline
AU - Ferrara, Roberto
AU - Agte, Sarita
AU - Oh, Michael
AU - Mudad, Raja
AU - Jahanzeb, Mohammad
AU - Suzuki, Hiroyuki
AU - Besse, Benjamin
AU - Lopes, Gilberto
N1 - Funding Information:
Competing interests: L.M. served for advisory board/educational sessions for Bristol-Myers Squibb, AstraZeneca and Roche diagnostics, during the conduct of the study and outside the submitted work. Y.C. received research funding from Abbvie, Bristol-Myers Squibb, Biodesix, Lexent Bio, Freenome, Honoraria/Advisory Boards from Roche/Genentech, AstraZeneca, Foundation Medicine, Counsyl, Neogenomics, Guardant Health, Boehringher Ingelheim, Biodesix, immuneoncia, Hanmi, Merck and Takeda during the conduct of the study and outside the submitted work. D.P. served for advisory board/educational sessions for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, priME Oncology, Peer CME and Roche, received honoraria for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME and Roche and Clinical trials research fund from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure and Daiichi Sankyo, and received support for Travel/Accommodations from AstraZeneca, Roche, Novartis, prIME Oncology and Pfizer during the conduct of the study and outside the submitted work. R.M. served for advisory board for AstraZeneca, Boehringher Ingelheim, Guardant health and Novartis outside the submitted work. M.J. received research funding from Lilly, Abbvie, Genentech, grants and other from Abbvie, Novartis, Genentech, and Ipsen during the conduct of the study and outside the submitted work. B.B. received research funding from Abbvie, AMGEN, AstraZeneca, BIOGEN, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, Pharma Mar, Sanofi, Spectrum Pharmaceuticals, Takeda and Tiziana Pharma during the conduct of the study and outside the submitted work. G.L. received research funding from Merck during the conduct of the study and outside the submitted work. The authors whose names are listed immediately below certify that they have no affiliations with or involvement in any organisation or entity with any financial interest. W.P., N.O., D.K., D.S., E.A., C.C., R.F., S.A., M.O. and H.S.
Funding Information:
Funding: Funding support by Sylvester Comprehensive Cancer Center Fund.
PY - 2020/2/4
Y1 - 2020/2/4
N2 - Background: Accessible biomarkers are needed for immunotherapy in advanced non-small-cell lung cancer (NSCLC). We previously described a multivariate risk prediction model, the iSEND, which categorises advanced NSCLC patients treated with nivolumab into Good, Intermediate or Poor groups. This model was developed by using only clinical and analytical variables (sex, ECOG-performance status, neutrophil-to-lymphocyte ratio [NLR] and post-treatment delta NLR). Methods: An international database of 439 patients who received post-platinum PD-1/L1 monotherapies was collected for validation. Performance of the iSEND to different PD-L1 groups was compared by using time-dependent positive predictive value (PPV) for their mortality events. Results: Median follow-up was 18.2 months (95% CI: 15.9–19.6). The overall survival of the iSEND Good (HR = 0.31, 95% CI: 0.22–0.43, p < 0.0001) was superior to the iSEND Poor. Time-dependent PPV for mortality of iSEND Poor was superior to PD-L1 = 0% group at 12 (75 vs. 53%, p = 0.01) and 18 months (85 vs. 46%, p = 0.03). However, female gender did not independently associate with better outcome in the validation cohort. Conclusion: The iSEND model is associated with the outcome of post-platinum PD-1/L1 monotherapy in advanced NSCLC patients. The iSEND Poor demonstrated a superior performance to PD-L1 = 0% in negative prognostication. Prospective investigation and modelling with other significant parameters in a larger cohort are warranted.
AB - Background: Accessible biomarkers are needed for immunotherapy in advanced non-small-cell lung cancer (NSCLC). We previously described a multivariate risk prediction model, the iSEND, which categorises advanced NSCLC patients treated with nivolumab into Good, Intermediate or Poor groups. This model was developed by using only clinical and analytical variables (sex, ECOG-performance status, neutrophil-to-lymphocyte ratio [NLR] and post-treatment delta NLR). Methods: An international database of 439 patients who received post-platinum PD-1/L1 monotherapies was collected for validation. Performance of the iSEND to different PD-L1 groups was compared by using time-dependent positive predictive value (PPV) for their mortality events. Results: Median follow-up was 18.2 months (95% CI: 15.9–19.6). The overall survival of the iSEND Good (HR = 0.31, 95% CI: 0.22–0.43, p < 0.0001) was superior to the iSEND Poor. Time-dependent PPV for mortality of iSEND Poor was superior to PD-L1 = 0% group at 12 (75 vs. 53%, p = 0.01) and 18 months (85 vs. 46%, p = 0.03). However, female gender did not independently associate with better outcome in the validation cohort. Conclusion: The iSEND model is associated with the outcome of post-platinum PD-1/L1 monotherapy in advanced NSCLC patients. The iSEND Poor demonstrated a superior performance to PD-L1 = 0% in negative prognostication. Prospective investigation and modelling with other significant parameters in a larger cohort are warranted.
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U2 - 10.1038/s41416-019-0643-y
DO - 10.1038/s41416-019-0643-y
M3 - Article
C2 - 31761899
AN - SCOPUS:85075422305
VL - 122
SP - 340
EP - 347
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 3
ER -