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Final overall survival (OS) results from the phase III PAOLA1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)

Autores: Nagao, S.; Harter, P.; Leary, A.; Cropet, C.; Pignata, S.; Fujiwara, K.; González Martín, Antonio; Bogner, G.; Vergote, I.; Colombo, N.; Maenpaa, J.; Selle, F.; Schmalfeldt, B.; Scambia, G.; Guerra-Alia, E. M.; Lefeuvre-Plesse, C.; Belau, A.; Lortholary, A.; Gropp-Meier, M.; Pujade-Lauraine, E.; Ray-Coquard, I.
Título de la revista: ANNALS OF ONCOLOGY
ISSN: 0923-7534
Volumen: 33
Número: SUPPL 9
Páginas: S1503 - S1504
Fecha de publicación: 2022
Background In the PAOLA-1/ENGOT-ov25 (NCT02477644) primary analysis, adding ola to maintenance bev after first-line (1L) platinum-based chemotherapy (PBC) + bev led to a significant progression-free survival (PFS) benefit in AOC (HR 0.59, 95% CI 0.49¿0.72; P<0.001), particularly in pts with homologous recombination deficiency (HRD+; BRCA1/2 mutation [BRCAm] and/or genomic instability; Ray-Coquard et al NEJM 2019). Here, we report the prespecified final OS analysis. Methods Pts with high-grade AOC, in response after PBC + bev, were randomized 2:1 to ola tablets (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; 15 mo total) or placebo [pbo] + bev. OS (intent-to-treat [ITT] population) was a key secondary endpoint, with analysis planned for 3 years after the primary analysis as part of hierarchical testing. Results 537 pts were randomized to ola + bev and 269 to pbo + bev (median follow-up 61.7 and 61.9 mo, respectively; OS data maturity: 55.3%). Median OS in the ITT population was 56.5 mo with ola + bev vs 51.6 mo with pbo + bev (HR 0.92, 95% CI 0.76¿1.12; P=0.4118; OS at 5 y, 47.3 vs 41.5%). In HRD+ pts, OS was prolonged with ola + bev (HR 0.62, 95% CI 0.45¿0.85; OS at 5 y, 65.5 vs 48.4%), with benefit in HRD+ pts with or without a tumour BRCAm (tBRCAm; Table). No benefit was seen in HRD- pts (HR 1.19, 95% CI 0.88¿1.63). Subsequent PARP inhibitor therapy was received by 105 (19.6%) ola + bev pts vs 123 (45.7%) pbo + bev pts. Myelodysplastic syndrome, acute myeloid leukaemia and aplastic anaemia incidence, and new primary malignancy incidence, was respectively: ola + bev, 9 pts [1.6%] and 22 pts [4.1%]; pbo + bev, 6 pts [2.2%]) and 8 pts [2.9%]). Table: 176O. Conclusions Despite a high proportion of pts in the control arm receiving a PARP inhibitor post-progression, ola + bev provided a clinically meaningful improvement in OS for 1L HRD+ pts with and without a tBRCAm, confirming ola + bev as standard of care in this setting. Clinical trial identification NCT02477644.