Abstract 800P
Background
BRCA mutated recurrent platinum sensitive OC patients (pts) who received a maintenance poly-adenosine ribose phosphatase inhibitor (PARPi) show a lower-than-expected response to subsequent chemotherapy in retrospective trial analysis. What are real world outcomes for UK pts, including BRCA wild-type (WT)?.
Methods
Retrospective data analysis of OC pts who received subsequent chemotherapy following a PARPi (minimum 14 days) between 01/01/18-31/12/21 across 10 UK sites. Responses were evaluated by imaging/CA125 or clinical status, with DCR (defined as CR/PR or SD at first post-chemotherapy assessment, excluding pts with progression). Statistical tests used: Kaplan-Meier (OS and PFS) and Fisher’s Exact Test (DCR and ORR).
Results
311 OC patients: stage III (n = 180, 58%) and IV (n = 106, 34%). 21% were BRCA mutant (MT) (n = 64). PARPis included olaparib (n = 47, 15%), niraparib (n = 220, 71%) and rucaparib (n = 44, 14%), with median duration of use of 189 days (range 14-1351). First post-PARPi chemotherapy was platinum-based (PBC) in 72% (n = 223); 2nd line in 37% (n = 116), 3rd line 47% (n = 147), later line in 15% (n = 48). 234 pts had evaluable responses: ORR to first post-PARPi treatment was 28% for PBC, 27% for non-platinum chemotherapy (NPC) (non-significant, ns); DCR was 44% to PBC, 33% to NPC (ns), median PFS was 5.8 months (m) for PBC, 5.4 m for NPC (ns). Across the 311 pts, median OS was 17.4 m for PBC and 13.6m for NPC (HR 0.56, p = 0.001). Preliminary analysis shows no significant difference in duration of PARPi use, ORR, DCR, according to BRCA status. PFS/OS data will be presented with respect to number of lines and BRCA status. Limitations include retrospective non-trial based follow up. Table: 800P
Response to first post PARPi treatment in 227 pts with known BRCA status
Endpoint | First post PARPi treatment | |||||
Platinum based | Non-platinum based | |||||
BRCA MT | BRCA WT | BRCA MT | BRCA WT | |||
ORR (%) | 28 | 28 | OR = 0.99, p = 1 | 17 | 28 | OR = 0.53, p = 1 |
DCR (%) | 38 | 47 | OR = 0.70, p = 0.3 | 17 | 33 | OR = 0.41, p = 0.6 |
PFS (m) | 5.3 | 6.1 | HR = 0.84, p = 0.3 | 9.4 | 5.4 | HR = 1.0, p = 1 |
OS (m) | 18.0 | 17.2 | HR = 0.93, p = 0.7 | 15.6 | 13.1 | HR = 0.71, p = 0.4 |
Conclusions
UK OC patients show similar PFS, OS, ORR and DCR to subsequent treatment following maintenance PARPi irrespective of BRCA status.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
S. Howlett: Financial Interests, Personal, Invited Speaker: Merck. A.M. Berner: Financial Interests, Personal, Invited Speaker, Speak at non-promotional event in cancer genomics: Pfizer Oncology; Financial Interests, Personal, Invited Speaker, Recorded non-promotional video on genomics: Eisai. L. Tookman: Other, Personal, Advisory Board: AstraZeneca, Clovis Oncology; Financial Interests, Personal, Speaker, Consultant, Advisor: Tesaro; Financial Interests, Personal, Invited Speaker: Clovis Oncology, GSK, AstraZeneca, MSD. L.H. Cossar: Other, Personal, Advisory Board: Tesaro. R. Miller: Financial Interests, Personal, Advisory Board: GSK, AZD, Merck, Shionogi, Ellipses; Financial Interests, Personal, Invited Speaker: GSK, AZD, Clovis Oncology. M. Hall: Financial Interests, Personal, Advisory Board, Ad boards. speaker engagements: GSK; Financial Interests, Personal, Advisory Board, Ad boards: Amgen; Financial Interests, Personal, Advisory Board, Ad Boards: AZ; Financial Interests, Personal, Advisory Board, Ad Boards, speaker engagement: Clovis Oncology; Financial Interests, Institutional, Research Grant, Funding and drug for CeNtuRIOn clinical trial-Glasgow Clinical trials Unit: Clovis Oncology; Financial Interests, Institutional, Research Grant, Research funding and drugs for CeNtuRIOn clinical trial-Glasgow Clinical Trials Unit: BMS; Financial Interests, Institutional, Research Grant, Research Funding and drug for CoRinTh clinical trial-Cardiff clinical trials Unit: Merck. All other authors have declared no conflicts of interest.
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