Abstract LB-171: Randomized phase II trial comparing therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer: Preliminary results of the feasibility of the SHIVA trial.
Authors: Tourneau Christophe Le , Scholl Suzy , Mitry Emmanuel , Isambert Nicolas , Tredan Olivier , Delord Jean-Pierre , Goncalves Antony , Campone Mario , Gavoille Celine , Servois Vincent , Mariani Odette , Vincent-Salomon Anne , Gentien David , Frio Thomas Rio , Servant Nicolas , Romejon Julien , Bieche Ivan , Delattre Olivier , Paoletti Xavier , Kamal Maud 
Published: August 2014

Abstract
Background
Two recent studies suggest that a histology-independent approach consisting in selecting molecularly targeted agents based on the molecular profile of patients' tumors improves patients' outcome [Von Hoff et al., 2010; Tsimberidou et al., 2012]. However, the lack of randomization versus standard of care in these studies did not allow drawing robust conclusions.
Methodology
The SHIVA trial is a multicentric randomized proof-of-concept phase II trial comparing molecularly targeted therapy based on tumor molecular profiling versus conventional therapy in patients with any type of refractory cancer. The primary endpoint is progression-free survival. The molecular profile performed on a mandatory biopsy includes the assessment of 1) hot spots mutations using the AmpliSeq cancer panel on Ion Torrent/PGM (Life Technologies), 2) gene copy number alterations using Cytoscan HD/Affymetrix, and 3) expression of estrogen, progesterone and androgen receptors by IHC. The algorithm used by a Molecular Biology Board (MBB) to guide treatment in the experimental arm is presented in the Table. .
Results
Between 10/2012 and 01/2013, 63 patients have been included in the study. Results of the feasibility study are available for the 53 first patients. Biopsy was performed in 50 out of 53 patients (94%). Complications occurred in 1 patient (2%). Median time between the biopsy and the MBB was 26 days [range: 14-42]. Mutations, gene copy number alterations and IHC profile were obtained in 32 (64%), 34 (68%) and 45 (90%) patients, respectively. A molecular abnormality leading to randomization was present in 21 patients (42%).
Conclusions
The establishment of a comprehensive tumor molecular profile is safe, feasible and compatible with clinical practice. A molecular abnormality matching with the approved drugs available in the trial was present in 42% of patients.
Algorithm to guide therapy in the experimental arm Molecular abnormalities Type of molecular abnormality Molecularly targeted agents KIT, ABL, RET Activating mutation or amplification Imatinib PI3KCA, AKT1 Activating mutation or amplification Everolimus AKT2,3, mTOR, RAPTOR, RICTOR Amplification Everolimus PTEN Inactivating mutation and LOH Everolimus STK11 Inactivating mutation and LOH Everolimus BRAF Activating mutation or amplification Vemurafenib PDGFRA/B, FLT-3 Activating mutation or amplification Sorafenib EGFR Activating mutation or amplification Erlotinib HER-2 Activating mutation or amplification Lapatinib + Trastuzumab SRC Activating mutation or amplification Dasatinib EPHA2, LCK, YES Amplification Dasatinib ER, PR Protein expression &gt;10% Tamoxifen (or letrozole if contra-indication) AR Protein expression &gt;10% Abiraterone
Citation Format: Christophe Le Tourneau, Suzy Scholl, Emmanuel Mitry, Nicolas Isambert, Olivier Tredan, Jean-Pierre Delord, Antony Goncalves, Mario Campone, Celine Gavoille, Vincent Servois, Odette Mariani, Anne Vincent-Salomon, David Gentien, Thomas Rio Frio, Nicolas Servant, Julien Romejon, Ivan Bieche, Olivier Delattre, Xavier Paoletti, Maud Kamal. Randomized phase II trial comparing therapy based on tumor molecular profiling versus conventional therapy in patients with refractory cancer: Preliminary results of the feasibility of the SHIVA trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-171. doi:10.1158/1538-7445.AM2013-LB-171