LBA45 - Overall survival (OS) outcomes from NRG-GY004, a phase III study comparing single-agent olaparib or combination cediranib and olaparib to platinum (Plat) based chemotherapy in recurrent plat sensitive ovarian cancer (OvCa)

Background

In the NRG-GY004 (NCT02446600) primary analysis, neither olaparib (O) nor combined cediranib and olaparib (C+O) improved progression-free survival (PFS) compared to standard of care (SOC) plat therapy as treatment for relapsed plat sensitive ovca, although median PFS was longer in patients with gBRCAm (Liu et al., J Clin Oncol 2022). We now report the prespecified OS analysis.

Methods

Pts with plat sensitive high-grade serous or endometrioid, or BRCA-related, ovca were randomized 1:1:1 to SOC (carboplatin/paclitaxel; carboplatin/gemcitabine; or carboplatin/liposomal doxorubicin), O (300mg twice daily), or C+O (C 30mg daily + O 200mg twice daily), stratified by gBRCA status, PFI (6-12 vs >12 months), and prior anti-angiogenic therapy. OS was a secondary endpoint; analysis was specified to occur when at least 265 events had occurred cumulatively in the SOC and C+O arms.

Results

Between 4FEB2016 and 13NOV2017, 565 pts enrolled (187 SOC, 189 O, 189 C+O), and 528 pts initiated treatment (166 SOC, 183 O, 179 C+O). 23.7% of patients had gBRCAmt. Median follow-up was 66.5 months; 419 deaths had occurred. The hazard ratio (HR) for OS was 1.27 (95% CI 0.99-1.62, p = 0.06) between O and SOC and 1.12 (95% CI 0.87-1.43, p = 0.38) between C+O and SOC, with median OS of 32.7, 31.0, and 33.5 months for SOC, O, and C+O, respectively. In gBRCA pts, HR for OS was 1.39 (95% CI 0.80-2.42) for O vs SOC and 1.24 (95% CI 0.94-1.63) for C+O vs SOC, with median OS of 43.2, 41.3, and 44.8 mos for SOC, O, and C+O. In non-gBRCA pts, HR for these comparisons was 1.26 (95% CI 0.71-2.21) and 1.07 (0.82-1.40). 46 pts on SOC had non-protocol therapy before disease progression, including 36 pts receiving PARPi. 27.3% of pts on SOC, 7.9% on O, and 10.6% on C+O terminated OS follow-up early prior to death.

Conclusions

In NRG-GY004, neither O nor C+O improved OS compared to SOC as treatment for relapsed plat sensitive ovca. Hazard ratios for OS for both O and C+O exceeded 1 with wide 95% CIs that included 1. These findings must be interpreted with caution given the proportion of pts terminating follow-up early and the number of pts on the SOC arm who received off-protocol PARPi maintenance.

Clinical trial identification

NCT02446600.

Editorial acknowledgement

Legal entity responsible for the study

National Cancer Institute.

Funding

National Cancer Institute.

Disclosure

J.F. Liu: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Eisai, Genentech/Roche, GSK, Regeneron Pharmaceuticals, Zentalis; Financial Interests, Personal, Other, Consulting: Bristol-Myers Squibb; Financial Interests, Institutional, Local PI: 2X Oncology, Aravive, Arch Oncology, CytoMX Therapeutics, GSK, Impact Therapeutics, Regeneron, Zentalis; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Bristol-Myers Squibb, Clovis Oncology. U.A. Matulonis: Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Blueprint Medicines, Immunogen, Allarity, Boehringer Ingelheim, CureLab, GSK, Merck, NextCure, Novartis, Ovarian Cancer Research Alliance, Trillium; Financial Interests, Personal, Other, DSMB: Alkermes, Symphogen. E. Swisher: Financial Interests, Personal, Advisory Board: Ideaya; Financial Interests, Personal, Other, DSMB: Novartis; Financial Interests, Institutional, Other, Clinical trial support: GSK, Clovis Oncology, Plexxicon. N. Cloven: Financial Interests, Personal, Advisory Board: Toray Industries, GSK, Tarveda, Kartos, Zentalis, Umoja. C. Muller: Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Institutional, Research Funding: AstraZeneca, Genmab, VBL Therapeutics, Roche/Genentech, TapImmune, Linnaeus Therapeutics, Agenus, Incyte, Merck. R. Moore: Financial Interests, Personal, Other, Consulting: Fujirebio Diagnostics; Financial Interests, Personal, Research Funding: Angle plc. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, Travel Expense: Clovis; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. A.A. Secord: Financial Interests, Institutional, Local PI: AbbVie, Aravive, AstraZeneca, Clovis Oncology, Eisai, Ellipses Pharma, GSK, I-MAB Biopharma, Immunogen, Merck, OncoQuest, Roche/Genentech, Seagen Inc, VBL Therapeutics, National Cancer Trial Network; Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, OncoQuest; Non-Financial Interests, Personal, Steering Committee Member, AXLerate trial: Aravive; Non-Financial Interests, Personal, Steering Committee Member, AtTEnd trial: Hoffman-LaRoche; Non-Financial Interests, Personal, Steering Committee Member, OVAL trial: VBL Therapeutics; Non-Financial Interests, Personal, Steering Committee Member, FLORA-5 trial, QPT-ORE-004: CanariaBio. All other authors have declared no conflicts of interest.