Abstract 423: Pooled analysis of matching score and patient outcome in I-PREDICT and WINTHER studies
Authors: David Casadevall, Michal Marczyk, Xavier Monzonis, Lajos Pusztai, Joan Albanell
Journal: Cancer Research (2021)

Abstract Introduction: Comprehensive genomic profiling (CGP) of tumors is available at many specialized cancer centers, potentially allowing oncologists to individualize patient therapy based on tumor molecular features. However, clinicians still lack a systematic approach to deal with the wealth of information provided by CGP. The proportion of plausible drug-matched alterations over the total number of alterations detected by CGP (Matching Score, MS) has been postulated to predict the likelihood of patient benefit. We performed a systematic analysis of MS and its association with the outcome of patients treated according to tumor DNA alterations within two recent precision oncology trials. Materials and Methods: We downloaded the supplementary data from WINTHER (NCT01856296) and I-PREDICT (NCT02534675) studies. We included patients who received treatment for one or more single-gene alterations, excluding eight patients that received immunotherapy due to high tumor mutational burden, PD-L1 positivity or microsatellite instability. We used MS cut-offs of 0.25 (as in WINTHER) and 0.5 (as in I-PREDICT) and also MS as a continuous variable to study its association with clinical variables such as age, sex, tumor type, and number of previous treatment lines (Kruskall-Wallis and Wilcoxon-rank tests), as well as disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) (Cox proportional hazards models). Results: The pooled analysis included 144 patients. Median age was 60 years (range 21-86) and 64% had received ≥ 2 lines of therapy. Most patients had colorectal (37%), lung (14%), or breast (11%) tumors, and 58% were treated with 2 or more drugs. MS was not associated with any clinical variable nor with DCR. MS &amp;gt; 0.25 (n=98; 68%) was associated with longer PFS (median 3.5 vs. 1.9 months, HR [95%CI]: 0.60 [0.41-0.87]) but not with OS. In contrast, MS &amp;gt; 0.5 (n=41; 28%) was associated with longer OS (median 14.1 vs. 6.5 months, HR [95%CI]: 0.50 [0.29-0.54]) but not with PFS. As a continuous variable, increasing MS values were associated with better OS (HR [95% CI]: 0.43 [0.20-0.95]) and with a non-significant trend towards better PFS (HR [95% CI]: 0.54 [0.21-1.05]). In a multivariable model adjusted for Age and study, PFS/OS probabilities improved consistently with increasing MS values from 0 to 0.5. With MS values &amp;gt; 0.5, OS probabilities kept increasing while PFS probabilities plateaued. Conclusions: The significant and consistent relationship between MS and OS (in contrast with PFS) may be explained by patients with higher MS values having more targeted therapies available for successive treatment lines, although we cannot exclude the existence of other confounding prognostic variables. We note that, as better drugs are developed and new knowledge is incorporated into the clinic, the value of CGP will probably increase over time, improving the number of patients with actionable alterations and their outcome. Citation Format: David Casadevall, Michal Marczyk, Xavier Monzonis, Lajos Pusztai, Joan Albanell. Pooled analysis of matching score and patient outcome in I-PREDICT and WINTHER studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 423.