51P - Efficacy and safety by time to maintenance therapy treatment initiation in PRIMA/ENGOT-OV26/GOG-3012

Background

To help delay cancer recurrence, maintenance treatment (MT) with PARP inhibitors is recommended in patients (pts) with advanced ovarian cancer (OC) that responded to 1L platinum-based chemotherapy (PBCT). Because PARP inhibitors, including niraparib, are associated with early hematologic adverse events, understanding when to initiate MT after 1L PBCT to best optimize safety and efficacy is vital.

Methods

In the phase 3 PRIMA study, eligible pts had newly diagnosed advanced epithelial OC that responded to 1L PBCT. Pts were randomized 2:1 to receive either niraparib (nir) or placebo (PBO) MT within 12 wks after completion of the last dose of 1L PBCT. This post hoc analysis grouped pts by time from end of 1L PBCT to randomization (<8 vs ≥8 wks) and evaluated investigator-assessed progression-free survival (PFS) and safety outcomes (17 Nov 2021 clinical cutoff date; median follow-up, 3.5 years).

Results

Overall, 356 pts (nir, 236; PBO, 120) were randomized <8 wks after 1L PBCT and 377 pts (nir, 251; PBO, 126) were randomized ≥8 wks after 1L PBCT. Median time from the end of 1L PBCT to randomization (range): <8 wks subgroup, nir, 6.1 wks (0.3–7.9 wks) and PBO, 5.7 wks (1.1–7.9 wks); ≥8 wks subgroup, nir, 10.6 wks (8.0–28.0 wks) and PBO, 10.8 wks (8.0–26.14 wks). The PFS benefit of nir was similar in pts randomized <8 wks and ≥8 wks after the end of 1L PBCT (Table). The percentages of pts who experienced any-grade treatment-emergent adverse events (TEAEs) were similar across subgroups in both treatment arms (Table). In the nir arm, the percentages of pts who experienced TEAEs leading to dose interruptions and reductions were slightly higher in pts randomized <8 wks than in pts randomized ≥8 wks after the end 1L PBCT.Table: 51P

^aEfficacy evaluable pts. ^bSafety evaluable pts. 1L, first-line; nir, niraparib; PBCT, platinum-based chemotherapy; PBO, placebo; PFS, progression-free survival; pts, patients; TEAE, treatment-emergent adverse event.

Conclusions

Within the allowable 12-wk interval, efficacy and safety outcomes were generally similar regardless of time to MT initiation in PRIMA. Pt safety should be considered when beginning nir MT soon after 1L PBCT to allow for recovery from chemotherapy-induced myelosuppression.

Clinical trial identification

NCT02655016.

Editorial acknowledgment

Writing and editorial support, funded by GSK (Waltham, MA, USA) and coordinated by Hasan Jamal, MSc, of GSK, was provided by Betsy C. Taylor, PhD, CMPP and Kathleen Blake, PhD, of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

GSK.

Funding

This study (NCT02655016) was sponsored by GSK, Waltham, MA, USA.

Disclosure

C.A. Haslund: Financial Interests, Personal, Other, Honoraria for lectures: AstraZeneca, BMS, GSK; Financial Interests, Personal, Advisory Board: GSK. L.J. Willmott: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, Immunogen, Merck, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca, Immunogen, Seagen. N. Cloven: Financial Interests, Personal, Advisory Board: Aadii, GSK, Kartos 2022, Novita pharmaceuticals 2023, Tarveda Therapeutics, Toray, Umoja 2022, Zentalis. H.F.M. Van den Bulck: Non-Financial Interests, Personal, Other, attending a meeting: MSD; Financial Interests, Personal, Advisory Board: Bayer. R.G. Moore: Financial Interests, Institutional, Other, Grants: Angle Plc; Financial Interests, Institutional, Other, Grant: Fujirebio Diagnostics; Financial Interests, Personal, Other: Fujirebio Diagnostics. R.E. O'Cearbhaill: Financial Interests, Institutional, Other, research support: NIH/NCI Cancer Center Support Grant (P30 CA008748); Financial Interests, Personal, Other, support grants: ArsenalBio, AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GSK, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Lyell Therapeutics, OnCusp Therapeutics, Regeneron, Sellas Life Sciences, Stemcentrx, Syndax, TapImmune, TCR2 Therapeutics; Financial Interests, Personal, Advisory Board: Bayer, Carina Biotech, Immunogen, Miltenyi, Loxo, Regeneron, R-Pharm, Seattle Genetics, Tesaro/GSK; Financial Interests, Personal, Other, personal fees: GOG Foundation; Financial Interests, Personal, Other, travel fees: Hitech Health; Non-Financial Interests, Personal, Other, steering committee member: DUO-O (olaparib) and PRIMA and Moonstone (niraparib) studies. F. Selle: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Clovis, GSK, MSD, Roche, PharmaMar; Financial Interests, Personal, Other, Travel support: AstraZeneca, GSK, MSD, Roche, PharmaMar. B. Pothuri: Financial Interests, Institutional, Other, Grant support: AstraZeneca, Celsion, Clovis Oncology, Duality Bio, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Seagen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, VBL Therapeutics; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, BioNtech, Clovis Oncology, Eisai, GOG Foundation, Lilly, Merck, Mersana, SeaGen, Sutro Biopharma, Tesaro/GSK, Onconova, Toray; Financial Interests, Personal, Other, Travel support: GSK, BioNtech. P. Harter: Financial Interests, Personal, Advisory Board, Value includes honoraria for lectures: AstraZeneca; Financial Interests, Personal, Advisory Board, includes honoraria for lectures: GSK, Roche, MSD; Financial Interests, Personal, Invited Speaker: Amgen, Stryker, Zailab, Eisai, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Clovis, Immunogen, Novartis, Mersana, Miltenyi; Financial Interests, Personal, Other, IDMC member: Sotio; Financial Interests, Personal, Expert Testimony: Exscientia; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Roche, GSK, Genmab, Immunogen; Financial Interests, Institutional, Funding: Seagen, Clovis; Financial Interests, Institutional, Other, Co-investigator: Novartis; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Other, Personal, Other, Travel support for conference: AstraZeneca. S. Ghamande: Financial Interests, Institutional, Other, Trial: Georgia Cancer Center; Financial Interests, Personal, Speaker’s Bureau, and Consulting: GSK, Eisai. P. Disilvestro: Financial Interests, Personal, Other: AstraZeneca, GSK, Immunogen; Financial Interests, Personal, Other, Travel support: AstraZeneca; Other, Personal, Other, leadership roles: GOG Foundation Board of Directors, NRG Oncology Board of Directors. M.P. Barretina Ginesta: Financial Interests, Personal, Other, consulting, educational activities, or advisory role fees: AstraZeneca, Clovis Oncology, Eisai, GSK, MSD, PharmaMar, Roche; Financial Interests, Personal, Other, Travel support: AstraZeneca, GSK, MSD, PharmaMar, Roche. A. Koliadi: Financial Interests, Personal, Other, consulting fees: Eisai, GSK. I. Malinowska, W. York: Financial Interests, Personal, Full or part-time Employment: GSK. A. González-Martín: Financial Interests, Personal, Other, fees for different educational or advisory-related activities: Alkermes, Amgen, AstraZeneca, Clovis, Eisai, Genmab, GSK, Hedera Dx, Immunogen, Illumina, Karyopharm, Mersana, MSD, Novartis, Novocure, Oncoinvent, PharmaMar, Regeneron, Roche, Seagen; Financial Interests, Personal, Invited Speaker: Sotio, Sutro, Takeda, Tubulis. B.J. Monk: Financial Interests, Personal, Other, consulting fees: Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOGFoundation, Gradalis, ImmunoGen, Iovance, Karyopharm, MacroGenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL; Financial Interests, Personal, Speaker’s Bureau, speakers’ bureau honoraria: AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, Tesaro/GSK. All other authors have declared no conflicts of interest.