Abstract 2953: Overall survival results of the single-institution molecular screening MOSCATO trial in hard-to-treat advanced cancers
Authors: Yolla El Dakdouki, Adrien Allorant, Loic Verlingue, Ludovic Lacroix, Etienne Rouleau, Nathalie Auger, Stefan Michiels, Thierry Debaere, Fabrice Andre, Gilles Vassal, Cecile Jovelet, Lambros Tselikas, Jean-Charles Soria, Antoine Hollebecque, Christophe Massard
Journal: Cancer Research (2018)

Abstract Background: MOSCATO 01 (NCT01566019) is a non-randomized single institution prospective clinical trial evaluating clinical benefit of integrating comprehensive molecular profiling into clinical practice to guide treatment in advanced cancers relapsing after standard therapies. The primary outcome of this trial has been previously published. We hereby evaluate the effect of having an actionable molecular alteration on overall survival (OS) in the adult patients (pts) included in MOSCATO 01 trial, and, among those with an actionable alteration, the effect of receiving a targeted therapy matched to a molecular alteration on OS. Methods: Survival data of pts who gave written consent to be included in MOSCATO 01 trial were used for this analysis. OS was defined from date of inclusion to death, or last visit at the institution. The Inverse Probability-of-Censoring Weighting method with a propensity score was used to estimate causal effects in a COX MODEL. For actionable alteration effect, propensity score included age, sex, Royal Marsden Hospital prognostic score. For targeted therapy effect, the same variables were used for propensity score and an additional landmark time was set at 2 months to take lead guarantee-time bias into account. Actionable molecular alterations were defined by a weekly molecular tutor board. Results: Between December 2011 and March 2016, among 1035 pts included in MOSCATO trial, 948 had a tumor biopsy. Of 843 pts where molecular portrait was successful, an actionable molecular alteration has been identified in 411 pts. Of the 411 pts with actionable molecular alteration, 199 received targeted therapy matched to the identified genomic alteration. At the cut-off date of June 2017, survival data was obtained for a total of 906 pts (396 out of 411 pts with an actionable alteration and 493 out of 624 pts without). After median follow-up of 9.2 months (4.7-20.4 months), 749 deaths were observed and median OS was 7.4 months. In the MOSCATO 01 trial, pts with an actionable molecular alteration had a significantly worse OS than pts without (HR=1.51 [1.38,1.64], p&amp;lt;0.001). Among pts with an actionable alteration, pts who received a matched targeted therapy did not have a significantly improved OS (HR=0.81 [0.65,1.01], p=0.06). Conclusion: In MOSCATO 01 trial, pts with an actionable target had significantly worse OS, while pts with a targeted treatment did not have a significantly better OS than those without. Randomized controlled trials are needed to evaluate whether customizing targeted therapy to pts with advanced tumors harboring actionable molecular alterations could improve OS. Citation Format: Yolla El Dakdouki, Adrien Allorant, Loic Verlingue, Ludovic Lacroix, Etienne Rouleau, Nathalie Auger, Stefan Michiels, Thierry Debaere, Fabrice Andre, Gilles Vassal, Cecile Jovelet, Lambros Tselikas, Jean-Charles Soria, Antoine Hollebecque, Christophe Massard. Overall survival results of the single-institution molecular screening MOSCATO trial in hard-to-treat advanced cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2953.