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Poster session 11

800P - Response to chemotherapy following PARP inhibition in UK ovarian cancer (OC) patients

Date

21 Oct 2023

Session

Poster session 11

Topics

Tumour Site

Ovarian Cancer

Presenters

Sarah Howlett

Citation

Annals of Oncology (2023) 34 (suppl_2): S507-S542. 10.1016/S0923-7534(23)01937-3

Authors

S. Howlett1, A.M. Berner2, K. Connolly3, A. Orosco Ttamina4, A. D'Angelo5, G. Gullick5, H.M.A. Abdallah6, J. Wood6, U. Mukherjee7, M. Azhar8, D. Lee9, P. Mahalingam10, L. Tookman10, L.H. Cossar11, R. Miller12, M. Hall13, S. Khalique14

Author affiliations

  • 1 Medical Oncology Department, Wexham Park Hospital, SL2 4HL - Slough/GB
  • 2 Barts Cancer Institute, London, Private Address - Dr. Alison Berner, EC1M 5PZ - London/GB
  • 3 Oncology, ECC - Edinburgh Cancer Centre - SCAN, EH4 2XU - Edinburgh/GB
  • 4 Oncology, St. Bartholomew's Hospital - Barts Health NHS Trust, EC1A 7BE - London/GB
  • 5 Oncology, Royal United Hospitals Bath - NHS Foundation trust, BA1 3NG - Bath/GB
  • 6 Oncology, University Hospitals of Leicester NHS Trust, LE1 5WW - Leicester/GB
  • 7 Oncology, UCLH - University College London Hospitals NHS Foundation Trust, NW1 2PG - London/GB
  • 8 Oncology, Leeds Cancer Centre, LS9 7LP - Leeds/GB
  • 9 Medical Oncology Department, Leeds Cancer Centre, LS9 7LP - Leeds/GB
  • 10 Medical Oncology Department, Imperial College London - Hammersmith Campus, W12 0NN - London/GB
  • 11 Medical Oncology, The Clatterbridge Cancer Centre - Liverpool, L7 8YA - Liverpool/GB
  • 12 Medical Oncology Department, UCLH - University College London Hospitals NHS Foundation Trust, NW1 2PG - London/GB
  • 13 Medical Oncology Dept., Mount Vernon Cancer Centre, HA6 2RN - Northwood/GB
  • 14 Oncology, Mount Vernon Cancer Centre, HA6 2RN - London/GB

Resources

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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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