Anti-angiogenic rechallenge combining bevacizumab and chemotherapy is efficient among relapse Ovarian Cancer (OC) patients (pts). However few data are available with tyrosine kinase inhibitors if progression during bevacizumab maintenance.
TAPAZ is a French randomized (2:1) phase II trial including recurrent OC pts during the first year of bevacizumab maintenance therapy in 1st or 2nd line, comparing weekly paclitaxel 65 mg/m2 with pazopanib 600 to 800 mg daily (PP arm) to weekly paclitaxel 80mg/m2 (P arm). Primary endpoint was Progression-Free-Survival (PFS). Main secondary endpoints were Overall Survival (OS), safety, pharmacokinetic, and Quality of Life (QoL).
116 pts were enrolled, 79 in PP and 37 in P arms. Median age was 65 y [42-85], relapse < 6months (mo) 70%, serous histology 88%, FIGO III/IV 98%. With a median follow-up of 12.8 mo [1-47], median PFS was 4.6 mo [3.9-6.1] in PP arm vs 5.5 mo [4.8-7.3] in P arm (p=0.6) and OS 13.5 vs 12.8 mo, respectively (p=0.77). Weekly median dose of Paclitaxel was 65 mg/m2 in PP arm and 80 mg/m2 in P arm. 14% of pts in PP arm received 800 mg of daily Pazopanib. 81% of pts in P arm stopped treatment because of progression vs 66% (p =0.09). G3/4 toxicities were more frequent in PP arm (87% vs 70%, p=0.03). Treatments discontinuation for toxicity was 47% in PP arm (including the 2 drugs in 19%) vs 12% in P arm (p<0.001). In PP arm, discontinuation was mainly due to digestive (31%), vascular (thrombosis, HBP) (28%) and hematologic (17%) disorders, with 3 sepsis and 2 toxic deaths (pulmonary embolism and digestive perforation). More significant deterioration of global QoL and diarrhea at 4 mo was reported in PP arm (mean change: -9 [-14; -3], p=0.003 and 11 [2-19], p=0.01, respectively). In PP arm, PFS and OS were not related to pazopanib plasma exposure at cycle 1 (p=0.7 and 0.5) but pts experiencing vomiting at cycle 1 had higher pazopanib exposure (p=0.01).
Addition of pazopanib to paclitaxel in recurrent OC pts progressing during bevacizumab maintenance is not superior to paclitaxel. It increases toxicity and compromises chemotherapy efficacy leading to more frequent early treatment discontinuations.
EudraCT 2014-003843-37; NCT02383251 (First posted: March 2015, Last Update: January 2020).
ARCAGY-GINECO.
ARCAGY-GINECO, Novartis.
F. Joly Lobbedez: Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Astellas; Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (institution), Advisory/Consultancy: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy: Clovis. M. Fabbro: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: GSK. D. Berton: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Travel/Accommodation/Expenses, ESMO: Pfizer; Travel/Accommodation/Expenses, ESCO: PharmaMar. A. Anota: Honoraria (self): Roche; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Sandoz; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Pfizer/Hospira; Travel/Accommodation/Expenses: Novartis. A. Puszkiel: Full/Part-time employment: Hospices Civils de Lyon, Groupement Hospitalier Sud. A. Floquet: Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: MSD; Travel/Accommodation/Expenses, Non-remunerated activity/ies: Roche. L. Bengrine Lefevre: Honoraria (institution), Full/Part-time employment: Centre Georges Francois Leclerc (hospital); Advisory/Consultancy: AstraZeneca. B. You: Honoraria (institution): HCL & Université de Lyon; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy: ECS Progastrin; Research grant/Funding (institution): Gineco. A. Lortholary: Honoraria (self): GSK; Honoraria (self): Roche; Honoraria (self): Novartis. D. Spaeth: Honoraria (self): Astra; Travel/Accommodation/Expenses: Pfizer. C. Abdeddaim: Advisory/Consultancy: GSK/Tesaro; Advisory/Consultancy: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck. M-C. Kaminsky-Forrett: Honoraria (self): Tesaro; Honoraria (self): AstraZeneca; Travel/Accommodation/Expenses: Merck. D. Petran: Travel/Accommodation/Expenses, Congrès, Réunions: Amgen; Travel/Accommodation/Expenses, Congrès, Réunions: Sandoz; Travel/Accommodation/Expenses, Congrès, Réunions: Pfizer; Travel/Accommodation/Expenses, Congrès, Réunions: Ipsen; Travel/Accommodation/Expenses, Congrès, Réunions: Roche; Travel/Accommodation/Expenses, Congrès, Réunions: BMS. P-E. Brachet: Advisory/Consultancy: BMS; Advisory/Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.
SOLO2 (ENGOT Ov-21; NCT01874353) demonstrated that maintenance olaparib (O) in patients (pts) with platinum-sensitive relapsed EOC and a
First subsequent treatment was analysed in pts who progressed according to RECIST1.1 in the O and placebo (P) arms. We conducted a post-hoc analysis of time to second progression (TTSP) calculated from the date of RECIST progression after O maintenance to next progression or death as a surrogate of first post-olaparib treatment progression-free survival.
106/195 (54%) and 80/99 (81%) pts had a RECIST progression in the O and P arms respectively. Pt baseline demographics were balanced between both arms
In this SOLO2 post-hoc comparison, some degree of resistance to standard subsequent platinum and non-platinum chemotherapy is noted in the O arm. However, the TTSP reduction being not at the expense of overall survival, it suggests that the earlier use of O remains optimal in this population. The best post O management should be studied in prospective manner.
NCT01874353.
AstraZeneca.
AstraZeneca.
J-S. Frenel: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BioCad; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis pharma SAS; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer Pharmaceuticals Israel; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Tesaro. D. Berton-Rigaud: Advisory/Consultancy, Board: AstraZeneca; Advisory/Consultancy, Board: Tesaro; Travel/Accommodation/Expenses, ESMO ASCO: Pfizer; Travel/Accommodation/Expenses, ESMO ASCO: PharmaMar. L. Vidal: Full/Part-time employment: Syneos Health ( CRO). P. Pautier: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: GSK. J.A. Ledermann: Honoraria (self), Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Artios; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Clovis Oncology; Advisory/Consultancy: Cristal Therapeutics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Tesaro; Speaker Bureau/Expert testimony: Tesaro/GSK; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): MSD Oncology. R.T. Penson: Honoraria (self), Advisory/Consultancy, Other Relationship: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Eisai Inc; Honoraria (self): Genentech/Roche; Honoraria (self), Advisory/Consultancy: Janssen Oncology (J & J); Honoraria (self), Advisory/Consultancy: Mersana Therapeutics, Inc.; Honoraria (self): Newlink Genetics; Honoraria (self), Advisory/Consultancy: Sutro Biopharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro Inc.; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Vascular Biogenics Ltd; Advisory/Consultancy: Amgen; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Care4ward; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Advisory/Consultancy: Merck; Research grant/Funding (institution): Array BioPharma; Research grant/Funding (institution): Cerulean Pharma; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Sanofi; Licensing/Royalties: Blackwell Publishing; Licensing/Royalties: BMJ; Licensing/Royalties: UpToDate. A.M. Oza: Honoraria (self): Intas; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Merck KGaA; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Immunovaccine; Non-remunerated activity/ies, Other Relationship: Clovis Oncology; Non-remunerated activity/ies, Other Relationship: Tesaro. J. Korach: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: MSD Oncology. S. Pignata: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Research grant/Funding (institution): MSD; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self): GSK; Honoraria (self): Clovis; Honoraria (self): PharmaMar; Honoraria (self): Incyte. N. Colombo: Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Roche/Genentech; Honoraria (self), Advisory/Consultancy: Tesaro; Advisory/Consultancy: BioCad; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: GSK; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Takeda. T-W. Park-Simon: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Lilly; Advisory/Consultancy: Daichi; Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: MS. K. Tamura: Research grant/Funding (self), Research grant/Funding (institution): Pfizer; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): MSD; Research grant/Funding (self): Chugai; Research grant/Funding (self): AstraZeneca. G.S. Sonke: Advisory/Consultancy, Research grant/Funding (institution): Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck Sharp & Dohme; Research grant/Funding (institution): Roche. A. Freimund: Licensing/Royalties, as CPI of the clinical trial, PRECISE, that is receiving study drug and part study funding: BeiGene Pharmaceuticals. C.K. Lee: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Takeda. E. Pujade-Lauraine: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self): GSK; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Incyte; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer/EMD; Advisory/Consultancy: Serono; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche. All other authors have declared no conflicts of interest.
Vel, a poly (ADP-ribose) polymerase inhibitor, is being evaluated for efficacy and safety in pts with newly diagnosed stage III or IV high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. We investigated the effect of Vel + chemotherapy followed by Vel maint on HRQoL in this population.
A phase III study (NCT02470585) examined efficacy of Vel (150 mg oral BID) plus carboplatin/paclitaxel (CP) for 6 cycles followed by maint with Vel 300/400 mg (
This analysis included 1069 pts (
Compared to CP alone, addition of Vel to CP followed by Vel maint showed smaller improvements in HRQoL scores from baseline. While early differences in TSE changes were noted, improvements were observed across both study arms in later cycles. TSW for HRQoL domains were similar across study arms. Thus, the addition of Vel to CP followed by Vel maint does not substantially affect HRQoL compared to CP alone.
NCT02470585.
Medical writing services, provided by Alan Saltzman of JK Associates, Inc., were funded by AbbVie.
AbbVie Inc.
AbbVie.
D. Cella: Advisory/Consultancy: AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Astellas; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: Pled Pharma; Advisory/Consultancy: Puma Biotechnology; Research grant/Funding (institution), Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: Astellas; Shareholder/Stockholder/Stock options: FACIT.org; Research grant/Funding (institution): Genentech. M. Bookman: Leadership role, Member, international protocol steering committee: AbbVie GOG3005; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Bayer; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer. K. Dahl Steffensen: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): AstraZeneca. R.L. Coleman: Research grant/Funding (institution): NCI-SPORE; Leadership role, Research grant/Funding (institution), Scientific Steering Committee: AstraZeneca; Leadership role, Research grant/Funding (institution), Scientific Steering Committee: Clovis; Leadership role, Research grant/Funding (institution), Scientific Steering Committee: Roche/Genentech; Research grant/Funding (institution): V-Foundation; Leadership role, Research grant/Funding (institution), Scientific Steering Committee: Janssen; Leadership role, Research grant/Funding (institution), Scientific Steering Committee: Merck; Research grant/Funding (institution): Novartis; Leadership role, Scientific Steering Committee: AbbVie; Leadership role, Scientific Steering Committee: Biomarin; Leadership role, Scientific Steering Committee: GamaMab; Leadership role, Scientific Steering Committee: Genmab; Leadership role, Scientific Steering Committee: Immunogen; Leadership role, Scientific Steering Committee: Pfizer; Leadership role, Scientific Steering Committee: Tesaro/GSK. M. Dinh, N. Khandelwal, K. Benjamin, R. Kamalakar, D. Sullivan: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. L. Floden, S. Hudgens: Full/Part-time employment: Clinical Outcomes Solutions.
Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that is approved for use in heavily pretreated pts and as maintenance treatment of pts with newly diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy (CT). Here we report PROs in pts receiving niraparib and placebo (PBO) in the PRIMA/ENGOT-OV26/GOG-3012 trial.
This double-blind, PBO-controlled, phase III study randomized 733 pts with newly diagnosed advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response (CR or PR) to first-line (1L) platinum-based CT. Pts received niraparib or PBO once daily for 36 months or until disease progression. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review. PROs, a secondary endpoint, were collected every 8 weeks for 56 weeks, then every 12 weeks thereafter while treatment was ongoing. Once a pt discontinued treatment, PRO evaluations were performed at the time of treatment discontinuation and then at 4, 8, 12, and 24 weeks (±1 week for each time point) after the end of treatment, regardless of the status of subsequent treatment. The validated PRO instruments utilized were FOSI, EQ-5D-5L, EORTC-QLQ-C30, and EORTC-QLQ-OV28.
Compliance rates were high for all of the PRO instruments used in the study. PRO analysis of the EORTC-QLQ-C30 and EORTC-QLQ-OV28 did not indicate a difference in health-related quality of life scores of pts treated with niraparib vs placebo. Mean scores between niraparib and placebo arms were similar at each time point. Overall, the health utility index showed a slight improvement trend in pts who received niraparib vs placebo.
Consistent with PRO results in the NOVA study, pts receiving niraparib in the PRIMA trial did not experience a decrease in quality of life compared with those receiving placebo.
NCT02655016.
Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Ashujit Tagde, PhD of GlaxoSmithKline, was provided by Eric Scocchera, PhD and Anne Cooper, MA of Ashfield Healthcare Communications (Middletown, CT, USA).
GlaxoSmithKline, Waltham, MA, USA.
GlaxoSmithKline, Waltham, MA, USA.
B. Pothuri: Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Tesaro; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology. D. Chase: Speaker Bureau/Expert testimony: Tesaro. F. Heitz: Non-remunerated activity/ies: NewOncology; Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy: Tesaro; Advisory/Consultancy: PharmaMar. R. Burger: Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Genentech; Advisory/Consultancy: Gradalis; Advisory/Consultancy: Janssen Research & Development; Advisory/Consultancy: Merck; Advisory/Consultancy: VBL Therapeutics. E. Guerra: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck Sharp & Dohme; Travel/Accommodation/Expenses: Baxter. J. Maenpaa: Honoraria (institution): Tesaro; Honoraria (institution): AstraZeneca; Honoraria (institution): Clovis; Honoraria (institution): Roche; Honoraria (institution): MSD; Honoraria (institution): OrionPharma. E. Bacqué: Full/Part-time employment: GlaxoSmithKline. Y. Li: Full/Part-time employment: GlaxoSmithKline. A. González Martín: Advisory/Consultancy, Non-remunerated activity/ies: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Tesaro; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy, Research grant/Funding (institution), Non-remunerated activity/ies: Roche Holding AG; Advisory/Consultancy: Merck & Co. Inc.; Advisory/Consultancy: Genmab; Advisory/Consultancy: Immunogen; Advisory/Consultancy: PharmaMar, S.A; Advisory/Consultancy: Oncoinvent AS. B.J. Monk: Advisory/Consultancy, Research grant/Funding (institution): Tesaro. All other authors have declared no conflicts of interest.
Newly diagnosed advanced OC pts are at high risk of relapse and 5-y survival is 30–50%. Delay of recurrence, prolonged survival and, for some patients, increased chance of cure are goals of treatment in this setting. In SOLO1 (NCT01844986; GOG-3004) pts with OC and a BRCAm who were in response after first-line platinum-based chemotherapy derived significant progression-free survival (PFS) benefit from maintenance olaparib vs placebo (pbo; median 41 months [m] f/u; median not reached vs 13.8 m; HR 0.30;
Pts received maintenance olaparib (tablets; 300 mg bid) or pbo for up to 2 y or until progression. PFS and recurrence-free survival (RFS) were investigator-assessed by modified RECIST v1.1. For pts in complete response (CR) at baseline, RFS was defined
260 pts were randomized to olaparib; 131 to pbo (median treatment duration 24.6 vs 13.9 m, respectively). After a median of 4.8 and 5.0 y of f/u, median PFS was 56 vs 14 m (Table). Among pts in CR at baseline, risk of disease recurrence or death was reduced by 63%. Additional secondary endpoints will be reported. *Pts had CR at baseline based on electronic case report form data.†Kaplan–Meier estimates. CI, confidence interval; HR, hazard ratio; NR, not reachedThe safety profile of olaparib was consistent with previous observations. No new cases of myelodysplastic syndrome or acute myeloid leukaemia were reported and incidence of new primary malignancies remained balanced between arms (olaparib, 7/260 [3%]; pbo, 5/130 [4%]).
PFS RFS* Olaparib N=260 Pbo N=131 Olaparib N=189 Pbo N=101 118 (45) 100 (76) 79 (42) 74 (73) 56.0 13.8 NR 15.3 0.33 (0.25–0.43) 0.37 (0.27–0.52) 87.7 51.4 91.0 58.0 73.6 34.6 77.2 39.0 60.1 26.9 64.0 28.9 52.3 21.5 55.2 23.0 48.3 20.5 51.9 21.8
For pts with a BRCAm and newly diagnosed advanced OC the benefit derived from 2 y of maintenance olaparib was sustained beyond the end of treatment and after 5 y almost half of pts were progression-free vs 20% with pbo. Over 50% of pts in CR after first-line platinum-based chemotherapy remained free from relapse 5 y later. 5-y f/u is the longest for any PARP inhibitor in this setting and no new safety signals were observed.
NCT01844986.
Medical writing assistance was provided by Elin Pyke, MChem, Mudskipper Business Limited, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
S. Banerjee: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. K.N. Moore: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Aravive; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (self): GSK/Tesaro; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Mersana; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy: Myriad; Advisory/Consultancy: Terveda; Advisory/Consultancy: VBL Therapeutics; Research grant/Funding (self): PTC Therapeutics; Research grant/Funding (self): Lilly. N. Colombo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Tesaro; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: PharmaMar; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Pfizer. A. Oaknin: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy: Genmab. M. Friedlander: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Beigene; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Advisory/Consultancy: Takeda; Non-remunerated activity/ies: AbbVie. A. Floquet: Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: MSD; Travel/Accommodation/Expenses, Non-remunerated activity/ies: Roche. A. Leary: Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Biocad; Advisory/Consultancy: Seattle Genetics. G.S. Sonke: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche. C. Gourley: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Nucana; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy: Foundation One; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Sierra Oncology; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Aprea. A. Oza: Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Clovis Oncology; Non-remunerated activity/ies: Tesaro. A. González Martín: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies, Principal investigator of PRIMA study sponsored by Tesaro: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer/Merck; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy, Speaker Bureau/Expert testimony: PharmaMar; Advisory/Consultancy: MSD; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Officer/Board of Directors, Chairman GEICO (Grupo Español Investigación Cáncer de Ovario): GEICO; Officer/Board of Directors, Chairman ENGOT (European Network for Gynecological Oncologic Trials): ENGOT. C. Aghajanian: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy: Eisai/Merck; Advisory/Consultancy: ImmunoGen, Inc.; Advisory/Consultancy: Mersana; Advisory/Consultancy: Roche; Advisory/Consultancy: Tesaro. W. Bradley: Advisory/Consultancy: Inovio. E. Holmes: Full/Part-time employment: AstraZeneca. E.S. Lowe: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. P. DiSilvestro: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro. All other authors have declared no conflicts of interest.
In the primary analysis of PAOLA-1/ENGOT-ov25 (NCT02477644), adding olaparib to maintenance bev after first-line platinum-based chemotherapy with bev led to a significant progression-free survival benefit in advanced HGOC pts (HR 0.59; 95% CI 0.49 -0.72) (Ray-Coquard et al.
Pts with newly diagnosed, FIGO stage III -IV HGOC in response after platinum-based chemotherapy plus bev randomized to olaparib tablets (300 mg bid for 24 months) + bev (15 mg/kg q3w for 15 months) or placebo + bev. PFS2 and time to second subsequent therapy or death (TSST) were key secondary endpoints (final PFS2 analysis planned for ≈53% data maturity or 1 year after primary analysis).
537 pts were randomized to olaparib + bev and 269 to placebo + bev with median PFS2 follow-up of 35.5 and 36.5 months, respectively (data cut-off 22 March 2020). Olaparib + bev provided a statistically significant reduction in the risk of second progression or death vs placebo + bev (ITT analysis; HR 0.78; 95% CI 0.64 -0.95; *tBRCAm and/or genomic instability. †Unstable due to lack of events. CI, confidence interval; ITT, intent to treat; HR, hazard ratio; HRD, homologous recombination deficiency; NR, not reached
PFS2 No. of events/no. of pts (%) Median, months HR (95% CI); Olaparib + bev Placebo + bev Olaparib + bev Placebo + bev ITT 260/537 (48) 164/269 (61) 36.5 32.6 0.78 (0.64–0.95); tBRCAm 41/157 (26) 36/80 (45) NR 45.0 0.53 (0.34–0.83) HRD positive* 85/255 (33) 70/132 (53) 50.3† 35.3 0.56 (0.41–0.77) HRD positive excluding tBRCAm 41/97 (42) 33/55 (60) 50.3† 30.1 0.60 (0.38–0.96) HRD negative 127/192 (66) 61/85 (72) 24.4 26.4 1.04 (0.77–1.42) HRD unknown 48/90 (53) 33/52 (63) 34.0 30.1 0.85 (0.55–1.33)
Adding maintenance olaparib to bev provided a benefit beyond first progression, with a substantial PFS2 benefit in tBRCAm and HRD-positive pts. The statistically significant improvement in PFS2 seen with olaparib + bev vs placebo + bev was supported by a similar TSST benefit.
NCT02477644.
Medical writing assistance was provided by Gillian Keating, MBChB, from Mudskipper Business Limited.
ARCAGY Research.
ARCAGY Research, AstraZeneca, Merck & Co., and F. Hoffmann-La Roche.
A. González Martín: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer/Merck; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pharmamar; Advisory/Consultancy: MSD; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Non-remunerated activity/ies, Principal investigator of PRIMA study: Tesaro; Leadership role, Chairman GEICO (Grupo Español Investigación Cáncer de Ovario): GEICO; Leadership role, Chairman ENGOT (European Network for Gynecological Oncologic Trials): ENGOT; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Tesaro/GSK; Advisory/Consultancy: Amgen; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Advisory/Consultancy: Novartis. F. Heitz: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca; Travel/Accommodation/Expenses: Tesaro; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self): Clovis. R. Berger: Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Merck; Travel/Accommodation/Expenses: Biocad; Travel/Accommodation/Expenses: Clovis; Travel/Accommodation/Expenses: Advaxis; Honoraria (self): AstraZeneca; Advisory/Consultancy: PharmaMar. K. Yonemori: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Taiho; Honoraria (self), Advisory/Consultancy: Eisai; Advisory/Consultancy: Takeda; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono. I. Vergote: Honoraria (institution): Advaxis; Honoraria (institution): Eisai; Honoraria (institution): MSD Belgium; Honoraria (institution): F. Hoffman-La Roche; Honoraria (institution): Millennium Pharmaceuticals; Honoraria (institution), Research grant/Funding (self): Oncoinvent; Honoraria (institution): Sotio; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution), Research grant/Funding (self), Travel/Accommodation/Expenses: Genmab; Honoraria (institution), Travel/Accommodation/Expenses: PharmaMar; Honoraria (institution), Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (institution), Travel/Accommodation/Expenses: Immunogen; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Stichting tegen Kanker. J. Maenpaa: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis; Advisory/Consultancy: MSD; Advisory/Consultancy: Orion Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro/GSK. C. Costan: Advisory/Consultancy: AstraZeneca. U. Canzler: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Lilly. C. Zamagni: Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Research grant/Funding (self): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: PharmaMar; Advisory/Consultancy, Travel/Accommodation/Expenses: Celgene; Research grant/Funding (self), Travel/Accommodation/Expenses: Pierre Fabre; Research grant/Funding (self), Travel/Accommodation/Expenses: Istituto Gentilli; Advisory/Consultancy: Eisai; Advisory/Consultancy: Lilly; Advisory/Consultancy: Amgen; Advisory/Consultancy: QuintilesIMS; Research grant/Funding (self): Takeda; Research grant/Funding (self): Teva; Research grant/Funding (self): Medivation; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Array BioPharma; Research grant/Funding (self): Morphotek; Research grant/Funding (self): Synthon; Research grant/Funding (self): Seattle Genetics. E.M. Guerra-Alia: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Tesaro; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: AstraZeneca; Travel/Accommodation/Expenses: Baxter. C.B. Levaché: Honoraria (institution): Genomic Health; Honoraria (institution): Novartis; Honoraria (institution): Pfizer; Honoraria (institution): Roche. F. Marmé: Honoraria (institution), Advisory/Consultancy: AstraZeneca; Honoraria (institution), Advisory/Consultancy: Roche; Honoraria (institution), Advisory/Consultancy: Clovis; Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (institution), Advisory/Consultancy: Tesaro; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: EIASI; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genomic Health; Honoraria (self), Advisory/Consultancy: Celgene; Advisory/Consultancy: CureVac; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy, Paid to institution: Immunomedics. E. Kalbacher: Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses: Leopharma. N. De Gregorio: Advisory/Consultancy: Roche; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: GSK. N. Dohollou: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Research grant/Funding (institution), serving as PI of a clinical trial: BMS; Research grant/Funding (institution), serving as PI of a clinical trial: Boehringer Ingelheim; Research grant/Funding (institution), serving as PI of a clinical trial: Genomic Health; Research grant/Funding (institution), serving as PI of a clinical trial: MSD; Research grant/Funding (institution), serving as PI of a clinical trial: Novartis. I.L. Ray-Coquard: Honoraria (self), Advisory/Consultancy: Abbvie; Honoraria (self), Advisory/Consultancy: Agenus; Honoraria (self), Advisory/Consultancy: Advaxis; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: PharmaMar; Honoraria (self), Advisory/Consultancy: Genmab; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Honoraria (institution), Research grant/Funding (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Travel/Accommodation/Expenses: GSK; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Mersena; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck Sereno; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: Clovis; Advisory/Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.