Search

6066 Background: Knowledge regarding HRD status is becoming crucial to guide maintenance strategies for patients with newly diagnosed OC. Unfortunately, for patients (pts) treated with neoadjuvant chemotherapy (NACT), HRD testing on small biopsies from diagnostic laparoscopies (Dx Lap) or interval debulking has a high failure rate. At relapse, biopsies may not be feasible. Aim: Evaluate the feasibility and usefulness of HRD testing on cfDNA from ascites Methods: Pts enrolled in a prospective biological study (OvBIOMark) consented to analysis of biological samples obtained as part of routine diagnosis. cfDNA was extracted from 1-2ml of double-centrifuged fresh ascites and subjected to 1) targeted NGS including the most common somatic mutations in high grade ovarian cancer ( TP53) to confirm presence of tumor cfDNA and 2) SNParray for copy number (CN) analyses to calculate a genomic instability score (GIS) for HRD. Results: Thirty four ascites samples were collected from 25 pts with suspected or confirmed OC. For 15/25 pts samples were obtained at Dx Lap, and for 10 pts samples were obtained at relapse. Seven pts underwent repeat ascitic drains during treatment or at relapse. 97% (33/34) of ascitic samples had detectable cfDNA (median = 980ng, range:80-5730ng) even when obtained during chemotherapy. A deleterious mutation was identified in 87% (29/33) of samples with high allelic frequencies (median allelic frequency, AF = 60%; 3.3-87%), confirming that most of detected cfDNA was tumoral. The most common mutation was a TP53m (86%; 25/29). We have performed CN analysis on cfDNA from ascites on 17 of these patients to evaluate their HRD status. Ten pts had a high GIS (HRD+), and 7 pts a low GIS (HRD-). The 4 pts with confirmed BRCAm included in this study had a high GIS on ascites. When available from the same patient, the CN profiles derived from ascites cfDNA and tumor sampling were superimposable. Conclusions: Ascites yields large amounts of cfDNA, which can be confirmed as tumoral based on TP53 mutation detection. CN analysis on ascitic cfDNA is feasible and can be used to detect the same HRD scar as tumor testing. Ascites is frequent at diagnosis, especially in pts with inoperable disease planned for NACT and could provide a useful alternative to tumor for HRD and BRCA testing.

647 Background: During the last decade, 10 agents have been approved for the treatment of patients (pts) with mccRCC, and guidelines have been developed up to 3L. The aim of the study is to describe the potential benefit of therapies beyond 3L in clinical practice Methods: Retrospective data analysis was performed using IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes beyond 3L in mccRCC. Kaplan Meier estimation was applied for progression free survival (PFS) and overall survival (OS) Results: Between 2005 and 2016, 825 (80%) pts had mccRCC and were treated with targeted therapies, of which 517 (63%) had 2L, 271 (33%) had 3L, 145 (18%) had 4L and 75 (9%) had 5L of therapy. Baseline characteristics and treatments are displayed in Table 1. With a median follow-up of 29 months (mo) (min: 20 max: 51), for patients receiving 4L, the median PFS is 5 mo (95%CI 4 – 6) and the median OS is 15.5 mo (95%CI 12 – 21). Pts with International Metastatic Renal Cell Cancer Database Consortium (IMDC) score favourable (18%), intermediate (59%), and poor risk (23%) at 4L initiation had a median OS of 24 mo (95%CI 11 – NR), 16 mo (95%CI 12.6 – 24), and 8 mo (95%CI 6 – 15), respectively (p < 0.0036). Partial response (PR) and stable disease (SD) were achieved in 13% and 56% of 122 evaluable pts. With a median follow-up of 16 mo (min: 13 max: 37) in 5L, the median PFS is 4.5 mo (95%CI 3 – 6) and the median OS is 19.5 mo (95%CI 11 - 28). Pts with a poor IMDC score risk at 5L initiation (33%) had a median OS of 7 mo (95%CI 3 – 10) (p < 0.0001). PR and SD were achieved in 16% and 52% of 55 evaluable pts in 5L Conclusions: The approved agents remain active as 4L or 5L options for mccRCC in pts who can reach this situation. Interestingly, both PFS and OS appear to be very similar in 4L and 5L as compared to 3L. Therefore, we believe that selected pts may derive benefit from these treatments beyond the barriers of regulatory or reimbursement approval [Table: see text]