Integrating clinical and biological prognostic biomarkers in patients with advanced NSCLC treated with immunotherapy: the DEMo score system.

BACKGROUND

Several biomarkers have been separately described to select patients for immunotherapy (IO), but few studies integrate these markers. Di Maio, EPSILoN and the plasma microRNA signature classifier (MSC), are three different clinico, biochemical and molecular markers able to independently predict prognosis in non-small cell lung cancer (NSCLC).

METHODS

Complete data such as sex, histology, ECOG-PS, stage, smoking status, presence of liver metastasis, LDH and neutrophils-to-lymphocyte ratio were collected to generate Di Maio and EPSILoN. The MSC risk level was prospectively assessed in plasma samples collected at baseline IO. The 3 markers were integrated into the DEMo score system prospectively tested in a cohort of 200 advanced NSCLC patients treated with IO. Endpoints were overall survival (OS), progression-free survival (PFS) and overall response rate (ORR).

RESULTS

DEMo separated patients in 7-risk groups whose median OS had a trend ranging from 29.7 to 1.5 months (P<0.0001). When comparing patients with the lowest (n=29) and the highest (n=35) DEMo scores ORR was 45% and 3%, respectively (P<0.0001). Considering the 53 PD-L1 ≥50% patients, DEMo identified a group of 13 (25%) patients who benefit less from IO in terms of both OS (HR: 8.81; 95% CI: 2.87-20.01) and PFS (HR: 6.82; 95% CI: 2.57-18.10). Twelve out of 111 (11%) patients who most benefit from IO according to OS (HR: 0.21; 95% CI: 0.07-0.62) and PFS (HR: 0.28; 95% CI: 0.12-0.65) were identified by DEMo in the PD-L1 <50% group.

CONCLUSIONS

The DEMo prognostic score system stratified NSCLC patients treated with IO better than each single marker. The proper use of DEMo according to PD-L1 could improve selection in IO regimens.

Informations de copyright

2020 Translational Lung Cancer Research. All rights reserved.

Déclaration de conflit d'intérêts

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-231). AP reports grants from Italian Association for Cancer Research during the conduct of the study; personal fees from Roche, AstraZeneca and BMS outside the submitted work; in addition, AP has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. CP reports grants from Italian Association for Cancer Research during the conduct of the study; personal fees from BMS and MSD outside the submitted work; in addition, CP has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. GLR reports grants from Italian Association for Cancer Research during the conduct of the study; personal fees from BMS, MSD and AstraZeneca outside the submitted work; in addition, GLR has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. DS reports grants from Italian Association for Cancer Research during the conduct of the study; personal fees from BMS, AstraZeneca and Boehringer Ingelheim outside the submitted work; in addition, DS has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. RF reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, RF has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. GG reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, GG has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. ADT reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, ADT has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. GV reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, GV has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. MB reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, Marta B has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. RL reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, RL has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. BT reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, BT has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. FT reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, FT has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. VT has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. GS reports grants from Italian Association for Cancer Research during the conduct of the study; in addition, GS has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. MCG reports grants from Italian Association for Cancer Research during the conduct of the study; personal fees from Roche, AstraZeneca, BMS, MSD, International GmbH, Boehringer Ingelheim Italia S.P.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche and Takeda outside the submitted work; in addition, MCG has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. Mattia B reports grants from Italian Ministry of Health during the conduct of the study; in addition, Mattia B has a patent IT1406672 licensed to Gensignia LS, a patent IT1403685 licensed to Gensignia LS, and a patent IT1406866 licensed to Gensignia LS. The other author has no conflicts of interest to declare.