Actionable molecular alterations in advanced gynaecologic malignancies: updated results from the ProfiLER programme

• Published in: European journal of cancer (1990) 2019-09, Vol.118, p.156-165
• Main Authors: Varnier, Romain, Le Saux, Olivia, Chabaud, Sylvie, Garin, Gwenaëlle, Sohier, Emilie, Wang, Qing, Paindavoine, Sandrine, Pérol, David, Baudet, Christian, Attignon, Valéry, Pissaloux, Daniel, Heudel, Pierre, You, Benoit, Leyronnas, Cécile, Collard, Olivier, Trédan, Olivier, Bonnin, Nathalie, Long, Jérôme, Jacquin, Jean-Philippe, Cassier, Philippe A., Derbel, Olfa, Freyer, Gilles, Viari, Alain, Blay, Jean-Yves, Ray-Coquard, Isabelle
• Format: Article
• Language: English
• Subjects: aCGH; Cancer; Deoxyribonucleic acid; DNA; DNA sequencing; ErbB-2 protein; Genomes; Gynaecologic cancer; Gynecology; Hybridization; Life Sciences; Molecular targeted agents; Mutation; Next-generation sequencing; Patients; Precision medicine; Survival; Tumors
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2019.06.017

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). 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. 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. 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). •Analysis of somatic genomic alterations was feasible in routine practice in gynecologic oncology.•Actionable genomic alterations were identified in 42.4% of patients with advanced relapsed gynecologic malignancies. Recommended targeted therapies were initiated by 12.6% of patients.•Out of the 41 RTT lines initiated, eight (20%) had a partial response and other ten (24%) had a stable disease.