49MO - Updated progression-free survival (PFS) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) treated with rucaparib (RUC) in ATHENA-MONO

Background

RUC provided a sustained PFS benefit in pts with newly diagnosed advanced OC after first-line (1L) treatment in the ATHENA-MONO study (NCT03522246). We report updated PFS analyses (data cutoff 01 March 2024).

Methods

Pts with high-grade, FIGO stage III-IV OC with response to 1L treatment were randomized 4:1 to treatment with 600 mg BID RUC (N = 427) or placebo (PBO, N = 111) for up to 2 y. An exploratory analysis was done to evaluate updated investigator-assessed PFS (INV). It included the primary populations (homologous recombination deficiency [HRD] and intent to treat [ITT]), non-nested HRD subgroups, and low/high-risk pts according to FIGO stage/surgical outcome and surgery timing. For pts in complete response (CR) at baseline, recurrence-free survival was defined as time from randomization to disease recurrence (new lesions by imaging) or death.

Results

After a median of 4.0 and 3.5 y of follow-up, an additional 1.9 and 1.6 y of follow-up, respectively, median PFS was consistently longer or not reached (NR) in pts treated with RUC than with PBO in ITT populations as well as in the HRD subgroup and the non-nested HRD subgroups (Table). In the higher-risk subgroup 27.7% of RUC vs 8.6% of PBO-arm pts were progression-free at 4 y; in the lower-risk subgroup 41.9% vs 37.2% of pts, respectively, were progression free at this time point. Among pts in CR at baseline, risk of disease recurrence or death was reduced by 51%. The safety profile of RUC was consistent with that from the primary endpoint analysis (23 March 2022). Three new cases of myelodysplastic syndrome or acute myeloid leukemia were reported since the primary analysis; the incidence was the same in the RUC and PBO arms (<1%).Table: 49MO

LOH, loss of heterozygosity.

Conclusions

RUC maintained a clinically significant improvement in PFS with 4.0 y of follow-up in pts with newly diagnosed advanced OC in pts with both low and high risk of progression. No new safety signals were identified.

Clinical trial identification

NCT03522246.

Editorial acknowledgment

Medical writing support and editorial support funded by pharma& was provided by Gautam Bijur and Celia Nelson of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

pharma&.

Funding

pharma&.

Disclosure

R. Kristeleit: Financial Interests, Personal, Research Grant: Incyte; Financial Interests, Personal, Other, Honoraria/ Consultation Fees: Duke St Bio, Eisai, MSD, AstraZeneca, GSK, Clovis Oncology/pharma&, Basilea, Seattle Genetics, Tubulis, Shattuck Labs, Prokarium, Leucid, Celcuity, iTEOS; Financial Interests, Personal, Speaker’s Bureau: Eisai, MSD, AstraZeneca, GSK. D. O'Malley: Financial Interests, Personal, Advisory Role: Adaptimmune, Agenus, Arcus Biosciences, AstraZeneca, Atossa Therapeutics, BBI Healthcare, Celsion, Clovis Oncology, Corcept Therapeutics, DualityBio, Eisai, Elevar Therapeutics, Genelux, Genentech/Roche, GSK, GOGFoundation, Immunogen, Imvax, InxMed, Jazz Pharmaceuticals, Laekna Therapeutics, Merck, Mersana, Novartis, Novocure, Novocure, OncoC4, Onconova Therapeutics, Regeneron, Roche, Seagen, Sutro Biopharma, Takeda, Toray Industries, Umoja Biopharma, VBL Therapeutics, Verastem, Vincerx Pharma; Financial Interests, Personal, Funding: AbbVie, AbbVie/Stemcentrx, Acerta Pharma, Advaxis, Ajinomoto, Ajinomoto, Amgen, Arcus Biosciences, Array BioPharma, AstraZeneca, BBI Healthcare, BeiGene, Bristol Myers Squibb, Cerulean Pharma, Clovis Oncology, Deciphera, Eisai, EMD Serono, EMD Serono, Ergomed, Exelixis, Genentech/Roche, Genmab, GSK, Immunogen, Immunogen, Incyte, Iovance Biotherapeutics, Janssen Research & Development, Karyopharm Therapeutics, Leap Therapeutics, Ludwig Institute, Merck, Mersana, Novartis, NovoCure, OncoQuest, Pfizer, PharmaMar, Precision Therapeutics, Regeneron, Roche, Sanofi, Seagen, Sumitomo Dainippon Pharma Oncology, Inc., Sutro Biopharma, Tesaro, Tracon Pharma, Verastem. M. Lim: Financial Interests, Personal, Advisory Role: AstraZeneca, Boryung, CKD Pharm, Genexine, GI Innovation, Hospicare and Takeda; Financial Interests, Personal, Funding: AbbVie, Amgen, Astellas Pharma, BeiGene, Cellid, CKD Pharm, Clovis Oncology, Eisai, Genexine, GSK, Incyte, Incyte, Merck, MSD, OncoQuest, Pfizer and Roche. I. McNeish: Financial Interests, Personal, Advisory Board: Clovis Oncology, AstraZeneca, Epsila Bio, GSK/Tesaro, Roche, OncoC4, Theolytics, Scancell, BioNTech and Theolytics; Financial Interests, Personal, Funding: AstraZeneca. T.J. Herzog: Financial Interests, Personal, Leadership Role: GOG Foundation; Financial Interests, Personal, Advisory Role: Aravive; AstraZeneca; Caris MPI; Clovis Oncology; Eisai; Epsilogen; GSK; Johnson & Johnson; Merck; Mersana; Roche/Genentech; Seagen. T.N. Fehm: Financial Interests, Personal, Other, Honoraria: Amgen, Celgene, Daiichi Sankyo Pharmaceutical, Novartis, Pfizer and Roche; Financial Interests, Personal, Advisory Role: Amgen, Daiichi Sankyo Nordics, Novartis, Pfizer and Roche. R.L. Coleman: Financial Interests, Personal, Leadership Role: Onxeo; Financial Interests, Personal, Advisory Role: AbbVie; Agenus; Alkermes; Alkermes; AstraZeneca/MedImmune; Clovis Oncology; Eisai; Genentech/Roche; Genmab; GSK; GOG Foundation; Gradalis; Immunogen; Karyopharm Therapeutics; Merck; Merck; Novocure; OncoMed; OncXerna Therapeutics; Financial Interests, Personal, Ownership Interest: McKesson; Financial Interests, Personal, Funding: Amgen, AstraZeneca/MedImmune, Clovis Oncology, Immunogen, Lilly, Merck, Mirati Therapeutics, Pfizer, Regeneron and Roche/Genentech; Financial Interests, Personal, Other, Received Travel, Accommodations, Expenses: Array BioPharma, AstraZeneca/MedImmune, Clovis Oncology, Clovis Oncology, GOGFoundation, Merck, Research to Practice, Roche/Genentech, Sotio and Vaniam Group. T. Van Gorp: Financial Interests, Institutional, Advisory Role: AstraZeneca, BioNTech, Eisai, GSK, ImmunoGen/AbbVie, Incyte, Karyopharm, MSD/Merck, OncXerna Therapeutics, Seagen, Tubulis, Zentalis; Financial Interests, Institutional, Funding: Amgen, AstraZeneca and Roche; Financial Interests, Institutional, Other, Travel, Accommodations, Expenses: AstraZeneca, GSK, Immunogen, MSD/Merck and PharmaMar. Has served on speaker bureau with Eisai, GSK, ImmunoGen, MSD. All payments institutional.; Financial Interests, Institutional, Speaker’s Bureau: Eisai, GSK, ImmunoGen, MSD. A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca; has served on steering committees for Clovis Oncology, AstraZeneca (uncompensated), and Tesaro; Financial Interests, Personal, Advisory Role: AstraZeneca and GSK; Financial Interests, Personal, Principal Investigator: Clovis Oncology, AstraZeneca, and GSK. J. Buscema: Financial Interests, Personal, Funding: US Oncology Network; Financial Interests, Personal, Advisory Role: GSK. B. Gao: Financial Interests, Personal, Advisory Role: BeiGene, IMPAC Medical Systems, IMPAC Medical Systems and MSD. D. Lorusso: Financial Interests, Personal, Advisory Role: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Genmab, Amgen, Seattle Genetics, Immunogen, Merck Serono, Oncoinvest, Corcept Therapeutics, Sutro Biopharma; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis Oncology, GSK, MSD, PharmaMar; Financial Interests, Institutional, Funding, Research Funding: PharmaMar, Clovis Oncology, GSK, MSD, AstraZeneca, Genmab, Seattle Genetics, Immunogen, Incyte, Novartis, Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, PharmaMar, AstraZeneca, Clovis Oncology, GSK; Financial Interests, Personal, Other, uncompensated relationship: Gynecologic Cancer InterGroup. D. Shih: Financial Interests, Personal, Full or part-time Employment: pharma&. K. Fujiwara: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Daiichi Sankyo, Eisai, Genmab, Taiho Pharmaceutical, Takeda and Zeria Pharmaceutical; Financial Interests, Personal, Advisory Role: Eisai, Genmab, MSD, NanoCarrier, Seagen, Taiho Pharmaceutical and Takeda; Financial Interests, Personal, Funding, Research Funding: AstraZeneca, Genmab, MSD, Regeneron and Seagen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Genmab. B.J. Monk: Financial Interests, Personal, Other, Honoraria: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Bayer, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Serono/Merck, Genmab/Seattle Genetics, GOGFoundation, Gradalis, ImmunoGen, Iovance Biotherapeutics, Karyopharm Therapeutics, Macrogenics, Merck, M; Financial Interests, Personal, Advisory Role: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Bayer, Clovis Oncology, Eisai, Elevar Therapeutics, EMD Serono/Merck, Genmab/Seattle Genetics, GOGFoundation, Gradalis, Gradalis, ImmunoGen, Iovance Biotherapeutics, Karyopharm Therapeutics, Merck, Me; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis Oncology, Eisai, Merck, Roche/Genentech and Tesaro/GSK; Financial Interests, Personal, Funding, Research Funding: Advaxis, Amgen, Array BioPharma, AstraZeneca, Genentech, Immunogen, Janssen, Lilly, Morphotek, Novartis, Nucana, Pfizer, Regeneron and Tesaro. All other authors have declared no conflicts of interest.