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

Abstract

ObjectivesThe 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). MethodsThe 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. ResultsFrom 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. ConclusionMolecular 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).