4050 - DEMo: a prospective evaluation of a prognostic clinico-molecular composite score in NSCLC patients treated with immunotherapy.

Background

The DiMaio (D), EPSILoN (E) and plasma microRNA signature classifier (MSC), are 3 diverse clinico-biochemical and molecular scores able to independently predict prognosis in advanced non-small cell lung cancer (aNSCLC) patients (pts) treated with immunotherapy (IO). By assessing the ability of each test a combined score (SC) called DEMo was developed. The study aims to prospectively evaluate the prognostic value of DEMo in aNSCLC pts treated with IO.

Methods

We included in the analyses 166 aNSCLC pts treated in 1L (n = 47) and further-lines (n = 119) with IO at Istituto Nazionale Tumori of Milan. For all pts we obtained complete necessary data for both clinical SC: D (sex, histology, ECOG-PS stage, uses of platinum-based therapy at 1L and response to 1L) and E (ECOG-PS, Smoke, Liver, LDH, NL-ratio). MSC was prospectively evaluated in plasma samples collected at baseline IO and the risk level was assessed. Endpoints were median overall survival (mOS), progression-free survival (mPFS) and overall response rate (ORR). Kaplan-Meier and Cox model were used to generate survival curves and multivariate analyses, respectively.

Results

In multivariate analysis adjusted for age, sex, smoke and ECOG-PS each score remain independently significant for both PFS (D: HR = 1.99, CI95% 1.21–3.03, p = 0.007; E: HR = 1.87 CI95% 1.12 – 3.10, p = 0.016; MSC: HR = 1.56, CI95% 1.03–2.37, p = 0.0370) and OS (D: HR = 3.12, CI95% 1.80–5.41, p = 0.0001; E: HR = 2.21, CI95% 1.28–3.79, p = 0.0041; MSC: HR = 2.03, CI95% 1.30–3.17, p = 0.0019). DEMo separated patients in 4-risk groups (gr) based on the presence of 3–2–1–0 poor prognostic SC. Strata had 0%–7%–20%–46% 18 months (mo) PFS (p < 0.0001) and 0%–23%–44%–78% 18 mo OS (p < 0.0001). We further combined DEMo gr 3/2 and 0/1 for multivariate analysis: mPFS and mOS for gr 3/2 vs 0/1 were 2.1 vs 6.4 mo (HR = 2.06, CI95% 1.26–3.36, p = 0.0038) and 4.1 vs 20.3 mo (HR 3.17, CI95% 1.91–5.24, p < 0.0001). The ORR was 2.9 (CI95% 1.4–6.0) fold higher for gr 0/1 compare to 3/2 (p = 0.0034).

Conclusions

We created a composite clinic-molecular combined biomarker classifier able to better predict prognosis compared to each single SC and to select patients who less likely benefit from IO. DEMo could be a useful tool to guide choices in aNSCLC.

Clinical trial identification

The authors.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale Tumori of Milan, Italy.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.