33O - PRIMA/ENGOT-OV26/GOG-3012 study: long-term conditional PFS

Background

Niraparib (nir) showed a blinded independent central review–assessed PFS benefit as a first-line (1L) maintenance therapy (MT) in the primary analysis of PRIMA (data cut 17 May 2019) across biomarker subgroups, including a substantial benefit in patients (pts) with homologous recombination–deficient (HRd) tumours. These results were the basis for approval of nir as MT after response to 1L platinum-based chemotherapy (CT). Here we report investigator-assessed (IA) cPFS (the probability of remaining alive and progression free beyond a specified landmark) in PRIMA.

Methods

This double-blind, placebo (PBO)-controlled phase 3 trial evaluated nir in pts with newly diagnosed, advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer (OC) at high risk for relapse after a complete or partial response (CR or PR) to 1L platinum-based CT. Stratification factors were best response to 1L CT regimen (CR/PR), receipt of neoadjuvant CT (yes/no), and homologous recombination deficiency status (HRd or HRp/HRnd) per the Myriad myChoice® CDx PLUS assay. Pts received nir or PBO once daily (2:1 ratio). IA cPFS was analysed for the HRd and intention-to-treat (ITT) populations, using the 17 Nov 2021 data cut.

Results

The median follow-up time was 3.5 y. The estimated PFS rate at 4 y was 38% for nir-treated pts and 17% for PBO-treated pts in the HRd population and 24% (nir) vs 14% (PBO) in the ITT population. The 2-y cPFS probabilities beyond the 1- and 2-y landmarks were higher in the nir arm than in the PBO arm (HRd: 1 y: 62% vs 50%, 2 y: 74% vs 60%; ITT: 1 y: 54% vs 46%, 2 y: 67% vs 64%). Safety was previously reported (González-Martín, et al. Ann Oncol. 2022;33[suppl 7]:S789).

Conclusions

A durable PFS benefit (nir vs PBO) was observed up to 4 y after randomisation in the ITT and HRd populations, as determined by IA. Pts free from disease progression or death at the 2-y landmark had a high probability of remaining free from progression or death at 4 y, supporting the use of nir as a 1L MT. Table: 33O

^a95% CI were not calculated at time points with <10 pts.

Clinical trial identification

NCT02655016.

Editorial acknowledgement

Writing and editorial support, funded by GSK (Waltham, MA, USA) and coordinated by Pru Roaf of GSK, was provided by Betsy C. Taylor, PhD, CMPP, Tafara T.R. Kunota, PhD, and Dena McWain of Ashfield MedComms, an Inizio company (Middletown, CT, USA).

Legal entity responsible for the study

GSK (Waltham, MA, USA).

Funding

GSK (Waltham, MA, USA).

Disclosure

A.J. Gonzalez Martin: Financial Interests, Personal, Funding, manuscript funding: GSK; Financial Interests, Institutional, Research Grant: GSK, Roche; Financial Interests, Personal, Other, Consulting fees: Alkermes, Amgen, Genmab, ImmunoGen, MacroGenics, Merck Sharp & Dohme, Novartis, Oncoinvent, Pfizer/Merck, Sotio, Sutro; Financial Interests, Personal, Other, Consulting fees, honoraria fees, support for attending meetings: AstraZeneca, GSK, PharmaMar, Roche; Financial Interests, Personal, Other, Consulting fees, honoraria fees: Clovis Oncology. B. Pothuri: Financial Interests, Institutional, Research Grant: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, GSK, I-mab, Incyte, Karyopharm, Merck, Mersana, Sutro, Toray; Financial Interests, Personal, Other, Consulting fees: AstraZeneca, GSK, Merck, SeaGen; Financial Interests, Personal, Other, support for attending meetings: GOG Partners; Financial Interests, Personal, Advisory Board: Arquer Diagnostics, Atossa, Deciphera, Eisai, Elevar Therapeutics, GOG Foundation, I-mab, Lilly, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray, VBL Therapeutics. I.B. Vergote: Financial Interests, Institutional, Sponsor/Funding, corporate sponsorship research: Amgen, Roche; Financial Interests, Institutional, Research Grant, contracted research: Genmab, Oncoinvent AS; Financial Interests, Institutional, Other, consulting fee payments: Amgen (Europe) GmbH, AstraZeneca, Carrick Therapeutics, Clovis Oncology Inc, Deciphera Pharmaceuticals, Elevar Therapeutics, F. Hoffmann–La Roche Ltd, Genmab, GSK, Immunogen Inc, Mersana, Millennium Pharmaceuticals, MSD, Novocure, Oncoinvent AS, Octimet Oncology, Sotio, Verastem Oncology, Zentalis; Financial Interests, Personal, Other, consulting fees: Deciphera Pharmaceuticals, Jazz Pharmaceuticals, Oncoinvent AS; Financial Interests, Personal, Other, honoraria payments: Agenus, Aksebio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, F. Hoffmann–La Roche Ltd, Genmab, GSK, Immunogen Inc, Jazz Pharmaceuticals, Karyopharm, MSD, Novartis, Novocure, Oncoinvent AS, Seagen, Sotio; Financial Interests, Institutional, Other, institutional travel support: Amgen, AstraZeneca, MSD, Roche, Tesaro; Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals (2021), Eisai, F. Hoffmann–La Roche Ltd, Genmab, GSK, Immunogen Inc, MSD, Novartis, Novocure, Seagen (2021), Sotio. W. Graybill: Financial Interests, Personal, Advisory Board: GSK; Financial Interests, Personal, Speaker’s Bureau: GSK. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zai Lab; Financial Interests, Personal, Other, Consulting: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zai Lab; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, GSK; Financial Interests, Institutional, Funding: Apexigen, AstraZeneca, Deciphera, GSK, Ultimovacs; Financial Interests, Personal, Member of the Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm. C. McCormick: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Immunogen, Clovis, Merck. D. Lorusso: Financial Interests, Personal, Other, consulting fees, honoraria: Amgen, MSD; Financial Interests, Personal, Other, consulting fees, honoraria, support for attending meetings and/or travel: AstraZeneca, Clovis Oncology, GSK, PharmaMar; Financial Interests, Personal, Other, consulting fees: Genmab, Immunogen, Seagen; Financial Interests, Personal, Other, support for attending meetings and/or travel: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, Merck Serono, MSD, Oncoinvest, PharmaMar, Seagen, Sutro; Non-Financial Interests, Personal, Member of the Board of Directors: GCIG; Financial Interests, Personal, Other, medical writing support: Clovis Oncology, GSK, MSD, PharmaMar; Financial Interests, Institutional, Funding, institutional funding for work in clinical trials: AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, Incyte, MSD, Novartis, PharmaMar, Roche, Seagen. G. Freyer: Financial Interests, Personal, Other, honoraria and consulting fees: GSK. F. Backes: Financial Interests, Personal, Other, personal fees: Agenus, AstraZeneca, CEC Oncolgoy, Clovis, Eisai, GSK, Immunogen, Merck, Myriad; Financial Interests, Personal, Research Grant: BeiGene, Clovis, Eisai, Immunogen, Merck, Natera. F. Heitz: Financial Interests, Personal, Other, honoraria: AstraZeneca, GSK, NovoCure, PhramaMar, Roche; Financial Interests, Personal, Advisory Board: NovoCure; Financial Interests, Personal, Leadership Role: AGO study group. A. Redondo Sanchez: Financial Interests, Institutional, Research Grant: Eisai, PharmaMar, Roche; Financial Interests, Personal, Other, honoraria: AstraZeneca, Clovis, Eisai, GSK, MSD, PharmaMar; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Eisai, GSK, MSD, PharmaMar; Financial Interests, Personal, Invited Speaker, travel support: AstraZeneca, GSK, PharmaMar. R. Moore: Financial Interests, Personal, Other, personal fees: Abcodia Inc, Fujirebio Diagnostics Inc, Humphries Pharmaceutical; Financial Interests, Institutional, Research Grant: Angle Plc. C. Vulsteke: Financial Interests, Personal, Other, medical writing support: GSK; Financial Interests, Personal, Invited Speaker, consulting fees: Atheneum Partners, Bristol Myers Squib, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme; Financial Interests, Personal, Other, travel support: Pfizer, Roche. R.E. O'Cearbhaill: Financial Interests, Personal, Advisory Board: Bayer, Carina Biotech, Fresenius Kabi, Tesaro/GSK, Regeneron, Seattle Genetics, R-Pharm, Immunogen; Financial Interests, Personal, Other, personal fees: GOG Foundation; Financial Interests, Personal, Other, travel fees: Hitech Health; Non-Financial Interests, Institutional, Research Grant: AstraZeneca/Merck; Financial Interests, Institutional, Research Grant: Atara Biotherapeutics/Bayer, Genentech, Genmab, GSK, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Regeneron, Sellas Life Sciences, StemcentRx, Syndax, TapImmune Inc, TCR2 Therapeutics. I. Malinowska: Financial Interests, Personal, Full or part-time Employment: GSK. L. Shtessel: Financial Interests, Personal, Full or part-time Employment: GSK. W. York: Financial Interests, Personal, Full or part-time Employment: GSK. B.J. Monk: Financial Interests, Personal, Other, consulting fees: Agenus, Akeso Biopharma, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novartis, Novocure, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, VBL; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, Tesaro/GSK.