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Multicenter Study
. 2024 Sep;9(9):103694.
doi: 10.1016/j.esmoop.2024.103694. Epub 2024 Sep 3.

Efficacy of chemotherapy after progression during or following PARPi exposure in ovarian cancer

A Xu-Vuillard  1 , C Guerin-Charbonnel  2 , F Bocquet  3 , S Cheeseman  4 , P M Kubelac  5 , M Zenatri  6 , G Hall  4 , P Achimas-Cadariu  7 , B Hanvic  8 , H Fenton  9 , A-M-L Sturz-Lazăr  10 , P Augereau  11 , I Ray-Coquard  8 , A Leary  12 , J-S Frenel  13
Affiliations
Multicenter Study

Efficacy of chemotherapy after progression during or following PARPi exposure in ovarian cancer

A Xu-Vuillard et al. ESMO Open. 2024 Sep.

Abstract

Background: Poly(ADP-ribose) polymerase inhibitors (PARPis) improved advanced ovarian cancer treatment. Most patients progress during or following PARPi exposure, however, with concerns about sensitivity of subsequent chemotherapy.

Patients and methods: In this international cohort study, we evaluated the efficacy of a subsequent chemotherapy following PARPi exposure in high-grade ovarian carcinoma patients. Endpoints included progression-free survival (PFS), overall survival and a multivariable Cox model was built to identify factors influencing PFS.

Results: We included 291 patients from four international centers treated between January 2002 and December 2021. The median number of previous chemotherapy was 1 (1.0-7.0), the median duration of PARPi exposure was 6.5 months (0.2-54.3 months). PARPi was used in first line in 14.1% patients. Most progressions occurred under PARPi exposure (89.1%). A BRCA pathogenic variant was identified in 130 patients (44.7%), absent in 157 patients (54.0%), and undocumented in 4 patients (1.4%). Platinum-based CT (PBC) and non-PBC were administered as subsequent treatments in, respectively, 182 patients (62.5%) and 109 patients (37.5%). Multivariable analyses showed that platinum-free interval (PFI) >6 months [adjusted hazards ratio (HR), 0.52; 95% confidence interval (CI) 0.39-0.70] and type of initial surgery (adjusted HR, 1.41; 95% CI 1.07-1.87; interval or closing surgery versus primary surgery) were associated with PFS, independent of BRCA status or line of therapy (≥2 versus 1). In patients with a PFI >6 months, PBC was numerically associated with the best PFS (adjusted HR, 0.68; 95% CI 0.46-1.01).

Conclusion: This is the largest real-world study assessing the efficacy of subsequent chemotherapy in patients progressing during PARPi exposure. The patients have poor outcomes. PBC is the best option in patients progressing on PARPi and eligible for PBC rechallenge (PFI >6 months).

Keywords: BRCA; PARPi; advanced ovarian cancer; platinum-based chemotherapy.

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Figures

Figure 1
Figure 1
Kaplan–Meier curves for PFS based on chemotherapy received after PARPi (A), BRCA status (B), platinum-free interval (C), and type of initial surgery (D). PARPi, Poly(ADP-ribose) polymerase inhibitor; PFI, platinum-free interval; PFS, progression-free survival.
Figure 2
Figure 2
Kaplan–Meier curves for OS based on chemotherapy received after PARPi (A), BRCA status (B), platinum-free interval (C), and type of initial surgery (D). OS, overall survival; PARPi, poly(ADP-ribose) polymerase inhibitor; PFI, platinum-free interval.
See this image and copyright information in PMC

References

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