The oncology landscape is rapidly evolving towards more personalized treatment with the use of molecular-driven therapies. Thus, genomic information has become an integral component of clinical decision-making. This study aims to analyze tumor tissue samples of high-grade serous ovarian cancer (HGSOC) to understand if genomic changes in gene mutation frequencies between primary and relapsing tumors occur and can influence the detection of actionable gene alterations.
A retrospective study approved by local Ethics Committee was conducted on OC patients treated at Fondazione Policlinico Universitario A. Gemelli, IRCCS. All subjects provided informed written consent for genetic analysis and study participation. FFPE specimens were analyzed by Foundation One® CDx, which applies NGS across 324 genes known to be drivers of solid tumors, by sequencing the coding regions of 309 cancer-related genes plus introns from 36 genes. Z-test was used to analyze the mutation frequencies between primary and relapsing tumors.
261 patients underwent Foundation Medicine testing. Out of 216 HGSOC, 151 tests were performed on primary lesion, 43 at 1st/2nd recurrence, and 22 at >3 recurrences. Statistically significant changes in BRCA1-2 frequencies were found between primitive lesions and recurrence (p=0.0013). A lower frequency in TP53 (p=0.0013) and a higher frequency of NF1 (p=0.028) and TERC (p=0.027) mutations were shown in tissue collected at recurrence compared to primary lesion. Selective chemotherapy pressure and natural enrichment of better prognosis patients at recurrence may explain the discrepancies between primary and secondary tumors.
These data suggest the opportunity to re-characterize the molecular profiling of the tumors at the time of recurrence to identify potentially actionable alterations to guide treatment.
The authors.
Has not received any funding.
V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline; Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company); Financial Interests, Institutional, Invited Speaker, ‘IsoMSLN’ in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic; Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca; Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.; Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG; Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd.; Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, GenMab; Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Personal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest.