Multicenter Real-World Data of Subsequent Chemotherapy after Progression to PARP Inhibitors in a Maintenance Relapse Setting
Por:
Romeo, M, Gil-Martin, M, Gaba, L, Teruel, I, Taus, A, Fina, C, Masvidal, M, Murata, P, Fernandez-Plana, J, Martinez, A, Perez, C, Garcia, Y, Rodriguez, V, Cros, S, Parera, M, Zanui, M, Catot, S, Pardo, B, Plaja, A, Esteve, A and Barretina-Ginesta, MP
Publicada:
1 sep 2022
Resumen:
Simple Summary Since the irruption of PARPi in the therapeutic armamentarium for ovarian cancer, concerns regarding post-progression treatment outcomes have emerged, owing to known crossed-resistance mechanisms between PARPi and platinum. In this multicentric retrospective series of ovarian cancer patients, we evaluated chemotherapy results upon progression to maintenance with PARPi in the relapsed setting. We further selected the population of platinum-sensitive patients (according to the classical definition) retreated with platinum (n = 74). In this platinum-sensitive population, overall response rate and survival outcomes of platinum rechallenge after PARPi were similar to historical series of the prePARPi era. However, within this group, analysis according to BRCA status showed that BRCA mutant patients (n = 35) presented higher rates of progression and worse survival outcomes under subsequent platinum than BRCA wild type patients (n = 39), with statistically significant differences. This is the largest real-world data series of ovarian cancer patients treated with platinum rechallenge in the post-PARPi scenario. Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8-17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6-9.2), and median OS (mOS) of 20.6 months (95% CI 13.6-28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2-22.2] and 10.3 [IQR 7.4-14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5-8.6) versus 7.5 months (95% CI 6.5-10.1, p = 0.03), and 16.4 (95% CI 9.3-27.5) versus 24.2 months (95% CI 17.2-NR, p = 0.036), respectively.
Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.
Filiaciones:
:
Inst Invest Germans Trias I Pujol IGTP, Inst Catala Oncol Badalona, Med Oncol Dept, Badalona Appl Res Grp Oncol BARGO, Carretera Canyet S-N, Badalona 08916, Spain
Gil-Martin, M:
IDIBELL, Inst Catala Oncol Hospitalet, Med Oncol Dept, Hosp Duran I Reynals, Gran Via 199-203, Lhospitalet De Llobregat 08909, Spain
Gaba, L:
Hosp Clin Barcelona, Med Oncol Dept, IDIBAPS, Translat Genom & Targeted Therapies Solid Tumors, Carrer Villarroel 170, Barcelona 08036, Spain
:
Inst Invest Germans Trias I Pujol IGTP, Inst Catala Oncol Badalona, Med Oncol Dept, Badalona Appl Res Grp Oncol BARGO, Carretera Canyet S-N, Badalona 08916, Spain
Taus, A:
IMIM Hosp del Mar Med Res Inst, Hosp del Mar CIBERONC, Med Oncol Dept, Canc Res Program, Passeig Maritim 25-29, Barcelona 08003, Spain
Fina, C:
Girona Biomed Res Inst IdIBGi, Inst Catala Oncol Girona, Med Oncol Dept, Av Franca S-N, Girona 17007, Spain
Masvidal, M:
Hosp Univ Reus, Med Oncol Dept, Avda Josep Laporte 2, Reus 43204, Spain
Murata, P:
Hosp Arnau Vilanova, Med Oncol Dept, Av Alcalde Rovira Roure 80, Lleida 25198, Spain
Fernandez-Plana, J:
Hosp Univ Mutua Terrassa, Med Oncol Dept, Pl Dr Robert 5, Terrassa 08221, Spain
Martinez, A:
Hosp Quiron Dexeux, Med Oncol Dept, Sabino de Arana 5-19, Barcelona 08028, Spain
Perez, C:
Xarxa Sanitaria & Social Santa Tecla, Med Oncol Dept, C Rambla Vella 14-16 4, Tarragona 43003, Spain
Garcia, Y:
Univ Autonoma Barcelona, Med Oncol Dept, Hosp Univ Parc Tauli, Inst Invest & Innovacio Parc Tauli I3PT, Carrer Parc Tauli 1, Sabadell 08208, Spain
Rodriguez, V:
Hosp Verge de la Cinta, Med Oncol Dept, Carrer Esplanetes 44, Tortosa 43500, Spain
Cros, S:
Hosp Gen Granollers, Med Oncol Dept, Avda Francesc Ribas S-N, Granollers 08402, Spain
Parera, M:
Hosp Univ Vic, Med Oncol Dept, Carrer Francesc Pla El Vigata 1, Vic 08500, Spain
Zanui, M:
Hosp Mataro, Med Oncol Dept, Carretera Cirera 230, Mataro 08304, Spain
Catot, S:
Xarxa Assistencial Univ Manresa, Med Oncol Dept, ALTHAIA, Dr Joan Soler 1-3, Manresa 08243, Spain
Pardo, B:
IDIBELL, Inst Catala Oncol Hospitalet, Med Oncol Dept, Hosp Duran I Reynals, Gran Via 199-203, Lhospitalet De Llobregat 08909, Spain
Plaja, A:
Inst Invest Germans Trias I Pujol IGTP, Inst Catala Oncol Badalona, Med Oncol Dept, Badalona Appl Res Grp Oncol BARGO, Carretera Canyet S-N, Badalona 08916, Spain
:
Inst Invest Germans Trias I Pujol IGTP, Med Oncol Dept, Badalona Appl Res Grp Oncol BARGO, Oncol Data Analyt Program ODAP,Inst Catala Oncol, Carretera Canyet S-N, Badalona 08916, Spain
Barretina-Ginesta, MP:
Girona Biomed Res Inst IdIBGi, Inst Catala Oncol Girona, Med Oncol Dept, Av Franca S-N, Girona 17007, Spain
Green Published, gold
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