Abstract 748P
Background
PARPi maintenance improves progression-free survival (PFS) and PFS to subsequent (ssq) CT in relapsed HGSEOC patients (p). Potential crossed PARPi/Pt resistance casts doubts on the benefit from ssq Pt after PARPi progression.
Methods
We recruited p receiving CT as the ssq line after progression to PARPi maintenance for relapsed HGSOEC, and at least 1 RECIST evaluation (cutoff 15 APR 2021). Endpoints: objective response rate (ORR), median PFS (mPFS) and median overall survival (mOS) (months, [mo]) to ssq Pt. Association to BRCA status, prior CT lines (2 vs ≥3), and best response to prior Pt (complete response [CR] vs partial or stabilization [PR/SD]) were explored (multivariate logistic regression and Cox regression models for ORR and survival, respectively).
Results
104p were identified (42 BRCA, 3 BRIP1, 3 RAD51, 2 CDK12, and 1 CHEK2 mutated), of which 59.6% were in their 3rd line. CR/PR/SD as best response to prior Pt were observed in 18.3%, 75.0%, and 6.7% p, respectively. Overall, 82 ssq Pt treatments were administered (79.3% CT-based doublets), 5 of them < 6 mo after the last cycle of prior Pt (excluded from the analysis*). For ssq Pt, ORR was 41.6%, and mPFS/OS were 6.6 (95%CI 5.1-8.3) / 20.6 (95%CI 14-28.4) mo, respectively. CR to prior Pt was a clinically relevant predictor of longer PFS (HR 1.82, 95%CI 0.9-3.68, p 0.094). The table shows results according to Pt-free interval (PFI) and ssq non-Pt subgroup. Findings were validated excluding 7p with SD to prior Pt. Table: 748P
| ssq CT (n=99*) | Non-Pt N=22 (%) | Pt, PFI 6-12 N=40 (%) | Pt, PFI>12 N=37 (%) | p |
| BRCAmut | 4 (18.2) | 12 (30.8) | 22 (62.9) | 0.004 |
| 2 prior CT lines (vs ≥3) | 14 (63.6) | 23 (57.5) | 22 (59.5) | 0.895 |
| CR as best response to prior Pt (vs PR/SD) | 2 (9.1) | 4 (10.0) | 13 (35.1) | 0.011 |
| Best response | 0.621 | |||
| CR | 0 (0.0) | 2 (5.0) | 4 (10.8) | |
| PR | 8 (36.4) | 12 (30.0) | 14 (37.8) | |
| SD | 5 (22.7) | 13 (32.5) | 7 (18.9) | |
| Progression | 9 (40.9) | 13 (32.5) | 12 (32.4) | |
| mPFS (mo, 95%CI) (events 86) | 4.8 (3.8-7.3) | 6.3 (4.5-8.8) | 7.1 (5.9-10.8) | 0.222 |
| mOS (mo, 95%CI) (events 52) | 10.7 (9.1-NA) | 16.6 (13-NA) | 26.6 (12-NA) | 0.037 |
Conclusions
Outcomes of ssq Pt compares favourably to data of late lines from historical prePARPi series. PFI to ssq CT stratifies p regarding their OS, but not PFS and ORR of ssq Pt.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Romeo Marin: Financial Interests, Personal, Expert Testimony, Educational purposes: MSD; Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Institutional, Invited Speaker: Tesaro; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: IMNG. M. Gil-Martin: Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Pharmama; Financial Interests, Personal, Sponsor/Funding: Roche, Pharmamar, MSD. L. Gaba Garcia: Financial Interests, Personal, Advisory Board: GSK, MSD, Clovis Oncology, AstraZeneca; Financial Interests, Personal, Advisory Board: PharmaMar; Financial Interests, Personal, Invited Speaker: GSK, MSD, Clovis Oncology, AstraZeneca. C. Fina: Financial Interests, Personal, Funding: GSK. Á. Taus: Financial Interests, Personal, Funding: BMS, AstraZeneca; GSK, MSD; Roche, Pfizer, Boehringer-Ingelheim. Y. García: Financial Interests, Personal, Invited Speaker: Roche, GSK-Tesaro, AstraZeneca and Clovis; Financial Interests, Personal, Advisory Board: Roche, GSK-Tesaro, AstraZeneca and Clovis. S. Cros Costa: Financial Interests, Institutional, Principal Investigator: Pfizer, Janssen; Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca; Roche, GSK, BMS, Merck, Janssen. B. Pardo Búrdalo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Clovis, GSK. M. Barretina-Ginesta: Financial Interests, Personal, Advisory Board: GSK, MSD, AstraZeneca, Clovis Oncology, Roche; Financial Interests, Personal, Speaker’s Bureau: GSK, MSD, AStra Zeneca, Roche, Pharmamar, Clovis Oncology. All other authors have declared no conflicts of interest.