Abstract 845P
Background
70% of pts with HGOC relapse within 3 years after debulking surgery (DS) and platinum doublet chemotherapy (CT). No currently used biomarkers or imaging studies can predict outcome following treatment. TP53m are identified in most pts with HGOC.
Methods
Pts with HGOC, enrolled in a prospective study (NCT03010124) consented to analysis of biological samples obtained throughout the disease course. ctDNA was extracted from 1-5ml of double-centrifuged plasma and analyzed using InVisionSeqTM to detect the presence of SNVs, indels and CNAs in 37 cancer-related genes, including TP53m.
Results
195 samples from 38 pts were collected at various time points during the disease course: at diagnosis, during CT, after DS or at relapse. A genomic alteration in ctDNA was identified in 134/195 (69%) samples. For 22 pts with a sample from initial diagnosis or relapse, ctDNA was detected in 14/14 pts (100%) and in 7/8 pts (88%) respectively. A sample was available immediately after DS in 13 pts. Pts with detectable ctDNA had a median progression free survival (PFS) 17.5 vs 26.4 months for pts with undetectable ctDNA: HR 2.83 (95%CI, 0.6 -12.9). Longitudinal ctDNA samples were available for 19 pts. For 10/19 pts, TP53m allelic frequency (AF) increased, or a new TP53m appeared: 6 during neo-adjuvant CT, among them 3 failed to have DS, 4 at relapse. The detection of a new TP53m or an increase in AF preceded biological and radiological relapse by a median of 5.2 (-0.4-22.2) and 6.2 months (1.1-21.2) respectively and was significantly associated with worse outcome as compared to its decrease or disappearance: PFS 8 versus 20.4 months, HR 3.71 (CI 95% 1.2-11.42) (p=0.02) and OS 29 versus 54.6 months, HR 1,38 (CI95% 0.38-4.9).
Conclusions
The detection of TP53m in ctDNA after DS is significantly associated with poor outcome. The increase in AF or appearance of a new TP53m during neoadjuvant CT may predict failure to achieve complete DS. ctDNA preceded biological or radiological relapse by at least 6 months. In HGOC pts, TP53m in ctDNA could be used as an early surrogate marker of treatment failure, can help identify pts who should benefit from maintenance treatment or escalation to eliminate minimal residual disease.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Inivata.
Disclosure
K. Howarth, C. Morris: Shareholder/Stockholder/Stock options, Full/Part-time employment: Inivata. P. Pautier: Advisory/Consultancy: Roche, AstraZeneca, Tesaro, Clovis and Genentech; Research grant/Funding (institution): PharmaMar; Travel/Accommodation/Expenses: Roche, AstraZeneca and Tesaro. E. Colomba-Blameble: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Sanofi, GSK; Travel/Accommodation/Expenses: Novartis. A. Leary: Honoraria (self): Medscape; Advisory/Consultancy: AZ, Clovis, GSK, Biocad, ability pharma, Merck Serono, Tesaro, MSD, Seattle Genetics, Gamamabs, Gritstone; Research grant/Funding (self): Inivata, Sanofi; Travel/Accommodation/Expenses: AZ, Roche, Clovis, Tesaro. All other authors have declared no conflicts of interest.