Abstract 530P
Background
Niraparib (nir) has shown PFS benefit as a first-line (1L) maintenance therapy (MT) in the PRIMA primary analysis (data cut 17 May 2019) in all subgroups regardless of biomarker status. These results were the basis for approval of nir as MT after response to 1L platinum-based chemo (CT). Here we report updated long-term efficacy and safety in the PRIMA study.
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) with 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 (NACT; yes/no), and homologous recombination deficiency (HRD) status (HRd/HRp/HRnd) per Myriad myChoice HRD test. Pts received nir or PBO QD (2:1 ratio). The primary endpoint of PFS by blinded independent central review was concordant with investigator assessment (INV). Updated (ad hoc) data are by INV, as of 17 Nov 2021.
Results
Of 733 randomized pts (nir, 487; PBO, 246), 373 (51%) were HRd (nir, 247; PBO, 126), and 249 (34%) were HRp (nir, 169; PBO, 80). Overall, 35% had stage IV disease, 67% received NACT, and 33% had a PR to 1L CT. As of 17 Nov 2021, median PFS follow-up time was 3.5 y. Nir-treated pts (HRd/HRp/overall) received continued PFS benefit vs PBO (Table). All subgroups showed a sustained and durable treatment effect. The most common grade ≥3 adverse events in the nir arm were thrombocytopenia (40%), anemia (32%), and neutropenia (21%). No related on-treatment deaths occurred. MDS/AML were reported at the same incidence in nir 6/484 (1.2%) and PBO 3/244 (1.2%) arms. OS remains immature at 41% for the overall population; 33% of PBO vs 9% of nir pts received subsequent PARPi. Table: 530P
| Primary efficacy analysis 17 May 2019 | Updated efficacy analysis (INV) 17 Nov 2021 | ||
| BICR | INV | ||
| Median PFS, mo | |||
| Overall Nir vs PBOHR (95% CI) p | 13.8 vs 8.20.62 (0.50–0.76)<0.0001 | 13.8 vs 8.20.63 (0.51–0.76)<0.0001 | 13.8 vs 8.20.66 (0.56–0.79)<0.0001 |
| HRd Nir vs PBOHR (95% CI) p | 21.9 vs 10.40.43 (0.31–0.59)<0.0001 | 21.9 vs 11.20.46 (0.34–0.63)<0.0001 | 24.5 vs 11.20.52 (0.40–0.68)<0.0001 |
| HRp Nir vs PBOHR (95% CI) p | 8.1 vs 5.40.68 (0.49–0.94)0.0203 | 8.3 vs 5.40.62 (0.45–0.85)0.0025 | 8.4 vs 5.40.65 (0.49–0.87)0.0038 |
| Estimated probability of no progressive disease or death for ≥4y | Overall Nir: 24%PBO: 14% HRd Nir: 38%PBO: 17% | ||
BICR, blinded independent central review; INV, investigator assessed.
Conclusions
Nir maintained clinically significant improvement in PFS with 3.5 y of follow-up in pts with newly diagnosed advanced OC at high risk of progression irrespective of HRD status. No new safety signals were identified.
Clinical trial identification
NCT02655016.
Editorial acknowledgement
Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Hasan Jamal, of GlaxoSmithKline, was provided by Nicole Renner, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA).
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline.
Disclosure
A.J. Gonzalez Martin: Financial Interests, Personal, Funding, Manuscript Funding: GSK; Financial Interests, Personal, Research Grant: GSK and Roche; Financial Interests, Personal, Other, Consulting Fees: Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, MacroGenics, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio, and Sutro; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis, GSK, PharmaMar, and Roche; Financial Interests, Personal, Other, Attended Meetings: from AstraZeneca, GSK, PharmaMar, and Roche. B. Pothuri: Financial Interests, Institutional, Research Grant: AstraZeneca, Celsion, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, Takeda Pharmaceuticals, Tesaro/GSK, and Clovis Oncology; Financial Interests, Personal, Other, Consulting Fees: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, and Tora; Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, Imab, Lily, Merck, Mersana, SeaGen, Sutro Biopharma, Tesaro/GSK, Toray, VBL Therapeutics; Financial Interests, Personal, Other, Leadership Fees: GOG Partners. I.B. Vergote: Financial Interests, Institutional, Sponsor/Funding, Corporate Sponsorship Research: Amgen and Roche ; Financial Interests, Personal, Other, Contracted Research: Genmab and Oncoinvent AS; Financial Interests, Personal and Institutional, Other, Institutional Consulting Fee Payment: 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 O; Financial Interests, Personal, Other, Consulting Fees: Deciphera Pharmaceuticals, Jazzpharma, Oncoinvent AS; honoraria payments from Agenus, Aksebio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, F. Hoffmann–La Roche Ltd, Genmab, GSK, Immunogen Inc, Jazzpharma, Karyopharm, MSD, Novartis; Financial Interests, Institutional, Funding, Travel Support: Amgen, AstraZeneca, MSD, Roche, and 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), and Sotio. W. Graybill: Financial Interests, Personal, Advisory Board: GlaxoSmithKline; Financial Interests, Personal, Invited Speaker: GlaxoSmithKline. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GlaxoSmithKline, Karyopharm, Merck, Roche, and Zai Lab; Financial Interests, Personal, Other, Consulting: AstraZeneca, Biocad, GlaxoSmithKline, Karyopharm, Merck, Roche, and Zai Lab; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca and GlaxoSmithKline; Financial Interests, Personal, Funding, Research Funding: Apexigen, AstraZeneca, Deciphera (trial chair), GlaxoSmithKline, and Ultimovacs; Financial Interests, Personal, Member of the Board of Directors: Karyopharm. C. Mccormick: Financial Interests, Personal, Other, Travel Support: AstraZeneca, Clovis, GSK, ImmunoGen, and Merck. D. Lorusso: Financial Interests, Personal, Other, Personal Fees: Amgen, AstraZeneca, Clovis Oncology, Genmab, Immunogen, Merck, and PharmaMar; Financial Interests, Personal, Research Grant: Merck and PharmaMar. G. Freyer: Financial Interests, Personal, Other, Personal Fees: AstraZeneca, Biogaran, Bristol-Myers Squibb, Clovis Oncology, MSD, Novartis, Pfizer Inc., Roche Holding AG, S.A.S, and Tesaro; Financial Interests, Personal, Research Grant: AstraZeneca, Mylan, and Roche Holding AG. F. Backes: Financial Interests, Personal, Other, Personal Fees: Agenus, CEC Oncology, Clovis, Eisai, Merck, and Tesaro; Financial Interests, Personal, Research Grant: Clovis, Eisai, Immunogen, and Merck. A. Redondo Sanchez: Financial Interests, Personal, Other, Institutional Grants: Eisai, PharmaMar, and Roche; Financial Interests, Personal, Other, Consulting Fees: Amgen, AstraZeneca, Clovis, GSK, PharmaMar, and Roche; Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Clovis, GSK, Novartis, PharmaMar, and Roche; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, PharmaMar, and Roche; Financial Interests, Personal, Other, Travel Support: AstraZeneca, GSK, Roche, and PharmaMar. R.G. Moore: Financial Interests, Personal, Other, Personal Fees: Abcodia Inc, Fujirebio Diagnostics Inc, and Humphries Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker, Institutional Grants: Angle Plc. C. Vulsteke: Financial Interests, Personal, Other, Consulting Fees: Atheneum Partners, Bristol Myers Squib, GSK, Janssen-Cilag, Leo-Pharma, Merck Sharp & Dohme, and Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, GSK, Janssen-Cilag, Leo Pharma, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel Support: Pfizer and Roche. R.E. O'Cearbhaill: Financial Interests, Personal, Advisory Board: with Bayer, Carina Biotech, Fresenius Kabi, GlaxoSmithKline, Regeneron, and Seattle Genetics; Financial Interests, Personal, Other, Personal Fees: GOG Foundation; Financial Interests, Personal, Other, Travel Fees: Hitech Health; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca/Merck, Atara Biotherapeutics/Bayer, Genentech, Genmab, GlaxoSmithKline, Gynecologic Oncology Group Foundation, Juno Therapeutics, Kite/Gilead, Ludwig Institute for Cancer Research, Regeneron, Sellas Life Sciences, StemcentRx, Syndax, TapImmune. I. Malinowska: Financial Interests, Personal, Other, Employee: GlaxoSmithKline. L. Shtessel: Financial Interests, Personal, Other, Employee: GlaxoSmithKline. N. Compton: Financial Interests, Personal, Other, Former Employee: GlaxoSmithKline; Financial Interests, Personal, Other, Consulting Fees: GlaxoSmithKline. B.J. Monk: Financial Interests, Personal, Other, Consulting Fees: Agenus, Akeso Bio, Amgen, Aravive, Bayer, Elevar, EMD Merck, Genmab/Seagen, GOGFoundation, Gradalis, ImmunoGen, Iovance, Karyopharm, Macrogenics, Mersana, Myriad, Novocure, Novartis, Pfizer, Puma, Regeneron, Sorrento, US Oncology Research, and VBL; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, Eisai, Merck, Roche/Genentech, and Tesaro/GSK. All other authors have declared no conflicts of interest.