Despite progresses in precision medicine, very few molecularly-targeted agents (MTA) are available for gynecologic cancer patients (pts). Objectives were to characterize tumor genomic alterations in the gynecological subpopulation of the ProfiLER program, to identify actionable alterations and to report clinical efficacy of MTA if used outside approved indications.
The ProfiLER program is a multicentric prospective trial to implement molecular profiling in pts with advanced disease. All potential pts with advanced gynecologic cancers were eligible. DNA extracted from either archival or fresh collected tumor samples was analyzed by targeted exon sequencing (NGS) of 59 cancer related genes and whole genome array comparative genomic hybridization (CGH). Genomic profiles were presented in a dedicated molecular tumor board (MTB) for recommendation of MTA when applicable.
Out of the 2184 included pts in the ProfiLER program, 242 pts with advanced gynecologic cancer were recruited from March 2013 to April 2016. For 211 (87%) pts (ovary, n = 136; cervix, n = 22; uterus, n = 45; others, n = 8), molecular analyses have been performed (median delay 2.8 months). 101 pts (48%) had at least one actionable alteration: PIK3CA (n = 23), KRAS (n = 10), ERRB2 (n = 9) and 50 other alterations. 109 MTA were recommended in 83 pts: PI3K/AKT/mTOR inhibitors (n = 46), sorafenib (n = 19), lapatinib (n = 7) and 17 other MTA (n = 37). 54 pts have not received MTA at the time of the analysis (poor PS or death, n = 25; stable disease, n = 15; no dedicated clinical trial, n = 7; other, n = 7). Currently, 29 pts initiated MTA. Partial response was reported for 8 pts (28%) and a stable disease at 3 months for 6 pts (21%). 12 pts (41%) progressed and 3 were non-evaluable. Median progression-free survival was 2.7 months (95% CI 1.9-5.4). Median overall survival was 64.8 months (38-101) for pts receiving MTA and 49.8 months (39-63) for pts not receiving MTA.
CGH and NGS identified actionable alterations on 48% of pts with gynecologic cancer and are feasible in routine practice. Nearly half of patients treated derived benefit from the recommended MTA, but these represent a minority of the whole screened population.
Clinical trial identification
Legal entity responsible for the study
Prof. Jean-Yves Blay, Centre Léon Bérard, Lyon (France)
Work funded by LYric (DGOS-INCa-4664). Aid granted by Bpifrance Financement abounded by European Community (E8983 – PREDICTIV).
O. Tredan: Honoraria, Consulting/Advisory, Travel funds: Lilly, Roche, Novartis, AstraZeneca, Pfizer, Celldex. P. Cassier: Research funding: Astrazeneca, Roche/Genentech, Novartis, Celgene, Blueprint, Lilly, Toray, MSD, Merck Serono, Transgene; Honoraria: Amgen, Astrazeneca, Elsalys. D. Perol: Corporate-sponsored research for Roche. All other authors have declared no conflicts of interest.