Association of combination tumor texture and vessel tortuosity with progression free survival across PD-L1 subgroups in durvalumab treated non-small cell lung cancer (NSCLC): Blinded validation results from CP1108.

8600 Background: Immunotherapy (IO) has shown a durable response with minimal toxicity in the treatment of metastatic NSCLC. However, only 30-50% of these patients (pts) actually respond. Despite initial optimism surrounding PD-L1 expression as a potential biomarker, IO provides benefit across PD-L1 low (<25%) and high (≥25%) status. This highlights a critical need for more effective biomarkers to guide treatment decisions. Here, we present blinded validation results of a CT-based biomarker of change in quantitative vessel tortuosity (1) (Δ-QVT) and texture radiomics (2) (Δ-Rad) between baseline (B) and 6 weeks post-treatment (TP1) for predicting response, overall survival (OS) and progression free survival (PFS) in CP1108 (NCT01693562). Methods: CT scans at B and TP1 were retrospectively analyzed from two studies (a) a multi-center training set (S tr , N=110) of metastatic NSCLC pts treated with first line IO and (b) a blinded NSCLC cohort of N = 151 pts treated with Durvalumab in CP1108 study (S v ). In S v , N=75 pts were PD-L1 high (S v + ) whereas N=65 pts were PD-L1 low (S v - ). An in-house MATLAB based algorithm was used to extract intra-tumoral, peri-tumoral texture and QVT features from up to two largest measurable tumors in each CT. A classifier (M Combo ) was trained on S tr to predict best overall response defined as per the RECIST v1.1 criteria using combination of Δ-QVT and Δ-Rad features. Area under the receiver operating characteristic (AUC) was used to evaluate M Combo against RECIST response whereas univariable and multivariable Cox regression models with log-rank test, hazard ratio (HR) with confidence interval (CI) and concordance index (C-index) were used to study the association of M Combo with OS and PFS in S v , S v + , and S v - . Results: M Combo predicted objective response with an AUC of 0.78 in S v and was statistically significantly associated with PFS (Table) in S v , S v + , and S v - . M Combo was associated with OS in S v , S v + , but not in S v - . Multivariable analysis with PD-L1 status, histological subtype, ECOG status, liver metastasis, line of therapy and sex showed independent association of M Combo across OS and PFS. Conclusions: Our results indicate that combination of radiomics and vessel tortuosity biomarker from CT is independently prognostic of response and PFS across PD-L1 levels. Prospective validation of this biomarker is needed. 1. Alilou et al. Sci Adv 2022. 2. Khorrami et al. Cancer Immunol Res 2020. Table: see text