Romain Varnier1, Olivia Le Saux2, Sylvie Chabaud3, Gwenaëlle Garin3, Emilie Sohier4, Qing Wang5, Sandrine Paindavoine6, David Pérol3, Christian Baudet4, Valéry Attignon5, Daniel Pissaloux7, Pierre Heudel2, Benoit You8, Cécile Leyronnas9, Olivier Collard10, Olivier Trédan2, Nathalie Bonnin11, Jérôme Long9, Jean-Philippe Jacquin10, Philippe A Cassier2, Olfa Derbel12, Gilles Freyer8, Alain Viari13, Jean-Yves Blay14, Isabelle Ray-Coquard15. 1. Medical Practices Evaluation Team - HESPER EA7425, Centre Léon Bérard, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France. 2. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 3. Department of Clinical Research, Centre Léon Bérard, Lyon, France. 4. Department of Translational Research, Centre Léon Bérard, Lyon, France; Synergie Lyon Cancer, Plateforme de Bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France. 5. Department of Translational Research, Centre Léon Bérard, Lyon, France. 6. Synergie Lyon Cancer, Plateforme de Bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France. 7. Université Claude Bernard Lyon 1, Lyon, France; Department of Biopathology, Centre Léon Bérard, Lyon, France. 8. Université Claude Bernard Lyon 1, Lyon, France; CITOHL, IC-HCL, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France. 9. Department of Medical Oncology, Institut Daniel Hollard, Grenoble, France. 10. Department of Medical Oncology, Institut Lucien Neuwirth, Saint-Priest-En-Jarez, France. 11. CITOHL, IC-HCL, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France. 12. Department of Medical Oncology, Centre Léon Bérard, Lyon, France; Department of Medical Oncology, Hôpital Privé Jean Mermoz, Lyon, France. 13. Synergie Lyon Cancer, Plateforme de Bioinformatique 'Gilles Thomas', Centre Léon Bérard, Lyon, France; INRIA Grenoble Rhône-Alpes, Montbonnot Saint-Martin, France. 14. Université Claude Bernard Lyon 1, Lyon, France; Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 15. Medical Practices Evaluation Team - HESPER EA7425, Centre Léon Bérard, Lyon, France; Université Claude Bernard Lyon 1, Lyon, France; Department of Medical Oncology, Centre Léon Bérard, Lyon, France. Electronic address: isabelle.ray-coquard@lyon.unicancer.fr.
Abstract
OBJECTIVES: The objectives of this study were to identify actionable genomic alterations in the gynaecological subpopulation of the ProfiLER programme and to report clinical efficacy of recommended targeted treatment (RTT). METHODS: The ProfiLER programme (NCT01774409) is a multicentric prospective trial aiming to implement molecular profiling in patients with advanced refractory cancers. In this programme, tumour DNA is analysed by targeted next-generation sequencing (69 genes) and by whole genome array comparative genomic hybridisation. Clinical cases and genomic profiles are presented in a dedicated molecular tumour board to guide treatment strategies. We report here an analysis of patients with gynaecological cancers included in this trial. RESULTS: From February 2013 to February 2017, 309 patients with gynaecologic cancer were included; 279 (90%) had sufficient quality, and 131 patients (42.4%) had at least one actionable genomic alteration in cancer cells. Four alterations were shared by at least 3% of the patients: 27 (9.7%) PIK3CA mutations, 15 (5.4%) KRAS mutations, 11 (3.9%) ERBB2 amplifications and 9 (3.2%) CDKN2A deletions. Forty-one treatments were initiated among 39 patients (12.6% of the screened population): 8 (20%) had a partial response, and other 10 (24%) had a stable disease. The median progression-free survival was 2.7 months. The median overall survival was 15.6 months for patients who received a RTT. CONCLUSION: Molecular profiling identified actionable alterations in 42.4% of patients with advanced refractory gynaecologic cancer, but only 12.6% were treated with a RTT. Among them, 46% derived clinical benefit (5.8% of the screened population).
OBJECTIVES: The objectives of this study were to identify actionable genomic alterations in the gynaecological subpopulation of the ProfiLER programme and to report clinical efficacy of recommended targeted treatment (RTT). METHODS: The ProfiLER programme (NCT01774409) is a multicentric prospective trial aiming to implement molecular profiling in patients with advanced refractory cancers. In this programme, tumour DNA is analysed by targeted next-generation sequencing (69 genes) and by whole genome array comparative genomic hybridisation. Clinical cases and genomic profiles are presented in a dedicated molecular tumour board to guide treatment strategies. We report here an analysis of patients with gynaecological cancers included in this trial. RESULTS: From February 2013 to February 2017, 309 patients with gynaecologic cancer were included; 279 (90%) had sufficient quality, and 131 patients (42.4%) had at least one actionable genomic alteration in cancer cells. Four alterations were shared by at least 3% of the patients: 27 (9.7%) PIK3CA mutations, 15 (5.4%) KRAS mutations, 11 (3.9%) ERBB2 amplifications and 9 (3.2%) CDKN2A deletions. Forty-one treatments were initiated among 39 patients (12.6% of the screened population): 8 (20%) had a partial response, and other 10 (24%) had a stable disease. The median progression-free survival was 2.7 months. The median overall survival was 15.6 months for patients who received a RTT. CONCLUSION: Molecular profiling identified actionable alterations in 42.4% of patients with advanced refractory gynaecologic cancer, but only 12.6% were treated with a RTT. Among them, 46% derived clinical benefit (5.8% of the screened population).