Abstract CT153: A multicenter, prospective trial in progress exploring the association between low level of genomic alteration and exceptional and unexpected response to targeted therapies in patients with solid tumors
Authors: Saux Olivia Le , Italiano Antoine , Spaeth Dominique , Heudel Pierre , Filleron Thomas , Albiges Laurence , Bachelot Thomas , Gonçalves Anthony , Pierga Jean-Yves , Barlesi Fabrice , Boige Valérie , Lebbé Céleste , Mortier Laurent , Frenel Jean Sébastien , Tredan Olivier , Jimenez Marta , Legrand François , Ferte Charles 
Published: August 2018

Abstract
Background: Most targeted therapies in cancer have reached approval based on clinical studies performed in unselected patients. Small subsets of patients present exceptional responses (ER), which could be driven by a low level of genomic alterations in genes identified as causally implicated in cancer.
Methods: This is an exploratory, multicenter, prospective trial conducted in adult patients with advanced solid cancers (breast cancer, lung adenocarcinoma or squamous cell carcinoma, colorectal cancer, ovarian cancer, renal clear cell cancer, skin cutaneous melanoma) having presented an ER to an approved antineoplastic targeted therapy will be included. ER is defined using the definition chosen by the NCI which combines the three criteria: - complete or partial response, - lasting &gt; 6 months, - and not expected in &gt; 10% of the patients in this drug - organ situation ER will be reviewed each month by the Response Confirmation Committee composed of the study coordinators and at least one expert of each organ. The primary objective is to identify whether tumors characterized by a low level of genomic alterations are associated with ER. A low level of genomic alteration is defined by the presence of less than the 5th quantile of genomic alterations to be expected in the given tumor type. For each tumor type, it is desired to test the null hypothesis H0: π=0.05 against the one-sided alternative hypothesis π&gt;0.05. For each of six cohorts, a sample size of 44 patients is necessary to achieve 80% power at π=15 with a one-sided level 5% test.
Results: As of January 2018, 152 patients were screened in 31 French centers. Forty-seven patients were included in the study (23 patients with breast cancer, 11 patients with kidney carcinoma, 5 with melanoma, 4 with lung cancer, 3 with colorectal cancer and 1 ovarian cancer). The 5 most frequent drugs were: sunitinib, everolimus, bevacizumab, trastuzumab and pazopanib. The EXPRESS study is still recruiting. Study completion date is estimated to be in August 2019.
Conclusion The identification of molecular traits associated with ER might serve the development of predictive classifiers for precision medicine. This study also represents a unique opportunity to better understand cancer biology.
Citation Format: Olivia Le Saux, Antoine Italiano, Dominique Spaeth, Pierre Heudel, Thomas Filleron, Laurence Albiges, Thomas Bachelot, Anthony Gonçalves, Jean-Yves Pierga, Fabrice Barlesi, Valérie Boige, Céleste Lebbé, Laurent Mortier, Jean Sébastien Frenel, Olivier Tredan, Marta Jimenez, François Legrand, Charles Ferte. A multicenter, prospective trial in progress exploring the association between low level of genomic alteration and exceptional and unexpected response to targeted therapies in patients with solid tumors [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 CT153.