Abstract 817P
Background
The CLIO trial (NCT02822157) randomized patients with relapsed ovarian cancer to Olaparib monotherapy (OLA) versus chemotherapy (CT) (ASCO 2019; SGO 2020). Here, we report the results of Olaparib monotherapy in relation to homologous recombination deficiency (HRD).
Methods
Patients with recurrent measurable disease and ≥1 prior line of chemotherapy were randomized 2:1 to OLA (300 mg tablets, BID) or CT. Patients with platin-sensitive ovarian cancer (PSOC) and a BRCA mutation known at randomization were excluded. Patients randomized to CT crossed over to OLA upon progression. FFPE samples of the primary tumor were used for somatic homologous recombination repair (HRR) mutational (MUT) analysis using the SureMASTR HRR assay and for HRD scarring analysis using an amplicon-based sequencing assay targeting ∼ 5000 SNPs genome-wide. HRR and HRD assays were developed by Agilent Technologies (Niel, Belgium) in close collaboration with the Leuven University. Both assays are for Research Use Only and not for use in diagnostic procedures.
Results
160 patients were randomized to OLA (n=107) or CT (n=53). Of the CT group, 44 patients crossed over to OLA at progression. Ultimately, 151 patients were treated with OLA (median follow-up 28.2 months). Median prior lines was 3 (range 1–9). ORR according to platin-sensitivity and detected HRR-MUT are presented in the table. Median progression-free survival (PFS) was 4.8 months; 7.6 and 2.8 months for PSOC and PROC (platin-resistant) respectively (HR 0.53, 95%CI: 0.36-0.78); 7.4 and 2.9 months for HRR-MUT and HRR-nonMUT respectively (HR 0.68, 95%CI; 0.43-1.09). Table: 817P
Response rates according to platin sensitivity and HRR-MUT
| All patients | Platin-resistant | Platin-sensitive | |
| All patients | 32/151 (21%) | 14/105 (13%) | 18/46 (39%) |
| BRCA mutated | 9/21 (43%) | 5/16 (31%) | 4/5 (80%) |
| BRCA wild type | 23/130 (18%) | 9/89 (10%) | 14/41 (34%) |
| HRR mutated | 9/27 (33%) | 5/21 (24%) | 4/6 (67%) |
| HRR wild type | 23/124 (19%) | 9/84 (11%) | 14/40 (35%) |
| BRCA1 | 8/18 (44%) | 4/13 (31%) | 4/5 (80%) |
| BRCA2 | 1/3 (33%) | 1/3 (33%) | - |
| BRIP1 | 0/3 (0%) | 0/2 (0%) | 0/1 (0%) |
| RAD51C | 0/2 (0%) | 0/2 (0%) | - |
| RAD51D | 0/1 (0%) | 0/1 (0%) | - |
Conclusions
OLA monotherapy showed an interesting efficacy in PSOC and PROC patients, also without the presence of HRR gene mutations. HRD scarring analysis performed by our group will be presented at the meeting.
Clinical trial identification
NCT02822157; July 4, 2016.
Editorial acknowledgement
Legal entity responsible for the study
Belgium and Luxembourg Gynaecological Oncology Group (BGOG).
Funding
AstraZeneca.
Disclosure
C. De Vogelaere, L. Heyrman, D. Goossens: Full/Part-time employment: Agilent Technologies. D. Lambrechts: Advisory/Consultancy: AstraZeneca. I.B. Vergote: Advisory/Consultancy: Advaxis, Eisai, MSD Belgium, Roche NV, Genmab, F. Hoffmann-La Roche Ltd, PharmaMar, Millennium Pharmaceuticals, Clovis Oncology, AstraZeneca NV, Tesaro, Oncoinvent AS, Immunogen, Sotio; Research grant/Funding (institution), Contracted Research (via KU Leuven): Oncoinvent AS, Genmab; Research grant/Funding (institution), Corporate-sponsored research: Amgen, Roche, Stichting Tegen Kanker; Travel/Accommodation/Expenses: Takeda Oncology, PharmaMar, Genmab, Roche, AstraZeneca, Tesaro, Clovis, Immunogen. All other authors have declared no conflicts of interest.