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- Jonathan A. Ledermann (London, United Kingdom)
- Alexandra Leary (Villejuif, France)
LBA29 - Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC)
- Isabelle L. Ray-Coquard (Lyon, France)
Abstract
Background
In the PAOLA-1/ENGOT-ov25 (NCT02477644) primary analysis, adding ola to maintenance bev after first-line (1L) platinum-based chemotherapy (PBC) + bev led to a significant progression-free survival (PFS) benefit in AOC (HR 0.59, 95% CI 0.49–0.72;
Methods
Pts with high-grade AOC, in response after PBC + bev, were randomized 2:1 to ola tablets (300 mg bid; up to 24 months [mo]) + bev (15 mg/kg q3w; 15 mo total) or placebo [pbo] + bev. OS (intent-to-treat [ITT] population) was a key secondary endpoint, with analysis planned for 3 years (y) after the primary analysis as part of hierarchical testing.
Results
537 pts were randomized to ola + bev and 269 to pbo + bev (median follow-up 61.7 and 61.9 mo, respectively; OS data maturity: 55.3%). Median OS in the ITT population was 56.5 mo with ola + bev vs 51.6 mo with pbo + bev (HR 0.92, 95% CI 0.76–1.12; *tBRCAm status by central labs; HRD status by Myriad myChoice HRD Plus §Preplanned exploratory analysis
No. of events/no. of pts (%) 5 y OS rate, % (95% CI) Ola + bev Pbo + bev Ola + bev Pbo + bev 288/537 (53.6) 158/269 (58.7) 47.3 41.5 0.92 (0.76–1.12) 93/255 (36.5) 69/132 (52.3) 65.5 48.4 0.62 (0.45–0.85) 48/157 (30.6) 37/80 (46.3) 73.2 53.8 0.60 (0.39–0.93) 44/97 (45.4) 32/55 (58.2) 54.7 44.2 0.71 (0.45–1.13) 195/282 (69.1) 89/137 (65.0) 30.6 34.9 1.14 (0.89–1.48) 140/192 (72.9) 58/85 (68.2) 25.7 32.3 1.19 (0.88–1.63)
Conclusions
Despite a high proportion of pts in the control arm receiving a PARP inhibitor post-progression, ola + bev provided a clinically meaningful improvement in OS for 1L HRD+ pts with and without a tBRCAm, confirming ola + bev as standard of care in this setting.
Clinical trial identification
NCT02477644.
Editorial acknowledgement
Medical writing assistance was provided by Rachel Dodd, PhD, at Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
ARCAGY Research.
Funding
ARCAGY Research, AstraZeneca, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and F. Hoffmann-La Roche.
Disclosure
I.L. Ray-Coquard: Financial Interests, Personal, Other, Honoraria: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Financial Interests, Institutional, Other, Honoraria: GSK, MSD, Roche and BMS; Financial Interests, Personal, Advisory Role: AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Financial Interests, Personal, Research Grant: MSD, Roche and BMS; Financial Interests, Institutional, Research Grant: MSD, Roche, BMS, Novartis, AstraZeneca and Merck Sereno; Financial Interests, Personal, Other, Travel: Roche, AstraZeneca and GSK. A. Leary: Financial Interests, Personal, Advisory Board: Zentalis; Financial Interests, Personal, Invited Speaker, Educational: GSK, Medscape, Onko+; Financial Interests, Institutional, Other, Steering committee: MSD; Financial Interests, Institutional, Advisory Board: GSK, AZ, Clovis, Ability Pharma, MSD, Tesaro, Merck Serono, Apmonia, Blueprint; Financial Interests, Institutional, Invited Speaker, Educational: Kephren publishing; Financial Interests, Institutional, Other, Consultancy: Orion; Financial Interests, Institutional, Invited Speaker: Tesaro, AZ, Clovis; Financial Interests, Personal, Other, Consultancy: GLG; Financial Interests, Institutional, Research Grant, PI translational research: ARCAGY-GINECO, Sanofi, AZ; Financial Interests, Institutional, Funding, CI clinical trial: AZ; Financial Interests, Institutional, Research Grant, Int CI clinical trial: OSE immuno; Financial Interests, Institutional, Funding, PI clinical trial: Agenus, BMS, Iovance, GSK; Financial Interests, Institutional, Funding, PI 5 clinical trials: Roche; Financial Interests, Institutional, Funding, PI 2 clinical trials: AZ; Financial Interests, Institutional, Funding, PI 3 clinical trials and steering committee: MSD; Non-Financial Interests, Institutional, Academic research project: Owkin, LXRepair; Non-Financial Interests, Personal, Proprietary Information, IDMC member: Clovis; Non-Financial Interests, Personal, Proprietary Information, IDMC chair: Pfizer. S. Pignata: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Merck Sharp & Dohme, Pfizer, Tesaro, Clovis Oncology, and PharmaMar. A.J. Gonzalez Martin: Financial Interests, Personal, Advisory Role: Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Merck Sharp & Dohme, macrogenmics, Novartis, Oncoinvent, Pfizer/Merck, PharmaMar, Roche, Sotio, and Sutro; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, PharmaMar, Roche, GSK, and Clovis; Financial Interests, Personal, Research Grant: Roche, and TESARO; Financial Interests, Personal, Other, Travel expenses: AstraZeneca, PharmaMar Roche, and TESARO. G. Bogner: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche and GSK; Financial Interests, Personal, Sponsor/Funding, Medical conferences: AstraZeneca, Roche and GSK. I.B. Vergote: Financial Interests, Personal, Other, Consulting/advidory: Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Seagen, Sotio; Financial Interests, Institutional, Research Grant: Oncoinvent AS, Amgen, Roche; Financial Interests, Personal, Other, Travel/accommodation: Karyopharm. N. Colombo: Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, Tesaro and PharmaMar; Financial Interests, Personal, Advisory Role: Roche/Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Takeda, Tesaro, BioCad and GSK. J. Maenpaa: Financial Interests, Personal, Other, Honoraria: AstraZeneca and GSK. F. Selle: Financial Interests, Personal, Other, Honoraria: AstraZeneca, GSK Tesaro, MSD, Sandoz (Novartis), and Clovis Oncology; Financial Interests, Institutional, Funding: Roche, GSK Tesaro, AstraZeneca, Immunogen, MSD, Incyte, and Agenus. B. Schmalfeldt: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Funding: Roche, AstraZeneca, Tesaro, Clovis, GSK, MSD; Financial Interests, Personal, Other, Travel/accommodation: Roche, AstraZeneca, Tesaro. G. Scambia: Financial Interests, Personal, Research Grant: MSD Italia S.r.l.; Financial Interests, Personal, Other, Consulting: Johnson & Johnson, and TESARO Bio Italy S.r.l; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology Italy Srl and MSD Italia Srl. E.M. Guerra Alia: Financial Interests, Personal, Advisory Role: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Other, Travel/accommodation: Roche, Tesaro: A GSK Company and Baxter. C. Lefeuvre-Plesse: Financial Interests, Personal, Other, Honoraria: Pfizer, AstraZeneca, Roche, Daiichi-Sankyo; Financial Interests, Personal, Other, Travel/accommodation: Roche, Novartis, Pfizer, Pierre Fabre. A. Belau: Financial Interests, Personal, Other, Honoraria: Roche, AstraZeneca, Clovis, MSD, Daiichi Sankyo Company, Lilly, Seagen; Financial Interests, Personal, Advisory Role: Pfizer, Roche, AstraZeneca, MSD, Lilly, Daiichi Sankyo Company, Seagen; Financial Interests, Personal, Other, Travel/accommodation: Roche, AstraZeneca, Daiichi Sankyo Company . A. lortholary: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD and Tesaro; Financial Interests, Personal, Invited Speaker, Honoraria: Clovis Oncology, and Roche; Financial Interests, Personal, Other, Participation in medical congress: Novartis, Pfizer, MSD, Lilly and Roche. E. Pujade-Lauraine: Financial Interests, Personal, Invited Speaker: AstraZeneca, Tesaro, and Roche, Clovis Oncology, Incyte, and Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Tesaro, and Roche; Financial Interests, Personal, Other, Travel: AstraZeneca, Tesaro, and Roche; Financial Interests, Personal, Full or part-time Employment: ARCAGY Research. P. Harter: Financial Interests, Personal, Other, Honoraria: straZeneca, Roche, Clovis Oncology, Stryker, MSD Oncology, Zai Lab, Lilly, Sotio, Esai, GlaxoSmithKline; Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Tesaro, Merck, GlaxoSmithKline, Clovis Oncology, Immunogen; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Genmab, GlaxoSmithKline, Immunogen, and Colvis Oncology. All other authors have declared no conflicts of interest.
517O - Overall survival (OS) at 7-year (y) follow-up (f/u) in patients (pts) with newly diagnosed advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) who received maintenance olaparib in the SOLO1/GOG-3004 trial
- Paul DiSilvestro (Providence, United States of America)
Abstract
Background
In the Phase III SOLO1/GOG-3004 trial (NCT01844986), maintenance olaparib provided sustained benefit beyond the end of treatment in pts with newly diagnosed advanced OC and a BRCAm. At 5-y f/u, median progression-free survival was 56.0 months [m] with olaparib vs 13.8m with placebo (pbo) (HR 0.33; 95% CI 0.25–0.43); 48% vs 21% of pts, respectively, were progression-free (KM estimates) (Banerjee
Methods
Pts who were in response to first-line platinum-based chemotherapy received maintenance olaparib tablets 300 mg bid or pbo for up to 2y or until progression. A descriptive analysis of OS, a secondary endpoint, was performed 7y after the last pt was randomized; prespecified final analysis of OS is planned at 60% data maturity.
Results
260 pts were randomized to olaparib and 131 to pbo (median treatment duration 24.6 vs 13.9m, respectively). At OS data maturity of 38.1% (data cut-off 7 Mar 2022), median OS was not reached in olaparib pts vs 75.2m in pbo pts, with an OS HR of 0.55 (95% CI 0.40–0.76; unadjusted for crossover; 44.3% of pbo pts received a PARP inhibitor in a subsequent line of therapy) (Table). At 7y, 45.3% of olaparib pts vs 20.6% of pbo pts were alive and had still not received a first subsequent treatment (KM estimates). The incidence of MDS/AML remained low and new primary malignancies remained balanced between arms (Table). *
Olaparib Pbo OS N=260 N=131 Median f/u, m 88.9 87.4 Events, n (%) 84 (32.3) 65 (49.6) Median OS, m NR 75.2 HR (95% CI) 0.55 (0.40–0.76) 0.0004* 7-y OS rate,† % 67.0 46.5 MDS/AML 4 (1.5) 1 (0.8) New primary malignancies 14 (5.4) 8 (6.2) Pneumonitis 5 (1.9) 0
Conclusions
2y of maintenance olaparib provided a clinically meaningful improvement in OS over pbo in pts with newly diagnosed advanced OC and a BRCAm. At 7y, 67.0% of olaparib pts vs 46.5% of pbo pts were alive; no new safety signals were detected. These data provide the longest f/u for any PARP inhibitor in this setting and support use of maintenance olaparib to achieve long-term remission and enhance the potential for cure.
Clinical trial identification
NCT01844986.
Editorial acknowledgement
Medical writing assistance was provided by Gillian Keating, MBChB, of Cence, funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
AstraZeneca.
Funding
This study was funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
S. Banerjee: Financial Interests, Institutional, Research Grant: AstraZeneca, GSK, Tesaro; Financial Interests, Personal, Funding, Personal and consulting fees: AstraZeneca, GSK, Amgen, Pfizer; Financial Interests, Personal, Funding, Consulting fees: Epsilogen, Genmab, ImmunoGen, Mersana, MSD, Merck Serono, Oncxerna, Roche; Non-Financial Interests, Personal, Advisory Board, Unpaid: Epsilogen; Financial Interests, Personal, Funding, Personal fees: Tesaro, Clovis Oncology, Takeda; Financial Interests, Personal, Funding, Travel: Nucana; Non-Financial Interests, Personal, Member, Director of Membership: unpaid: European Society of Medical Oncology . N. Colombo: Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Financial Interests, Personal, Funding, Personal and consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Merck Sharp & Dohme, Tesaro; Financial Interests, Personal, Funding, Consulting fees: Biocad, Roche, PharmaMar, ImmunoGen, Mersana, Oncxerna, Pfizer; Financial Interests, Personal, Funding, Personal fees: Novartis. G. Scambia: Financial Interests, Institutional, Research Grant: MSD Italia S.r.l.; Financial Interests, Personal, Funding, Consulting fees: Johnson & Johnson, Tesaro; Financial Interests, Personal, Speaker’s Bureau: Clovis Oncology. A. Oaknin: Financial Interests, Institutional, Research Grant: AbbVie Deutschland, Abililty Pharmaceuticals, Advaxis Inc, Aeterna Zentaris, Amgen SA, Aprea Therapeutics AB, Bristol Myers Squibb, Clovis Oncology Inc, Eisai Ltd, F, F. Hoffmann-La Roche Ltd, ImmunoGen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc., PharmaMar SA, Regeneron Pharmaceuticals, Tesaro; Financial Interests, Personal, Funding, Personal fees: Clovis Oncology Inc, Deciphera Pharmarceutia, Genmab, GSK, ImmunoGen, Mersana Therapeutic, Sutro; Financial Interests, Personal, Funding, Personal and travel fees: PharmaMar, AstraZeneca, Roche. M.L. Friedlander: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, GSK, Lilly, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, BeiGene; Financial Interests, Personal, Funding, Travel fees: AstraZeneca; Financial Interests, Personal, Funding, Personal lecture fees: GSK, Act Genomics; Financial Interests, Personal, Member: MSD, AGITG IDMSC; Financial Interests, Personal, Funding, Consulting fees: AbbVie. A. Floquet: Financial Interests, Personal, Funding, Travel fees: AstraZeneca. A. Leary: Financial Interests, Institutional, Research Grant: AstraZeneca, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, Ability Pharma, Biocad, Clovis Oncology, GSK , Medscape, Merck Serono, MSD, Touch Congress, Zentalis, ARIEL4 , TROPHIMMUNE; Financial Interests, Personal, Funding, Travel fees: AstraZeneca, Clovis Oncology, GSK, Roche; Financial Interests, Personal, Funding, Consulting fees: Seattle Genetics. G.S. Sonke: Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Roche; Financial Interests, Institutional, Funding, Consulting fees: Biovica, Seagen. C. Gourley: Financial Interests, Institutional, Research Grant: AstraZeneca, BergenBio, Clovis Oncology, GSK, Medannexin, MSD, Novartis, Nucana, Aprea, Tesaro; Financial Interests, Personal, Funding, Consulting fees: AstraZeneca, GSK, MSD, Tesaro; Financial Interests, Personal, Funding, Lecture fees: AstraZeneca, Clovis Oncology, GSK, MSD, Nucana, Tesaro, Chugai, Roche, Takeda, Cor2Ed; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, Nucana, Tesaro, Chugai, Roche; Financial Interests, Personal, Member: Scottish Medicines Consortium. A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca. A.J. Gonzalez Martin: Financial Interests, Institutional, Research Grant: GSK, Roche; Financial Interests, Personal, Funding, Consulting fees: GSK, Roche, Alkermes, Amgen, AstraZeneca, Clovis Oncology, Genmab, Immunogen, Mersana, MSD, Oncoinvent, PharmaMar, Sotio, Takeda; Financial Interests, Personal, Funding, Personal and travel fees: GSK, Roche, AstraZeneca, MSD, PharmaMar; Financial Interests, Personal, Funding, Personal fees: Clovis Oncology; Financial Interests, Personal, Member of the Board of Directors: GEICO, ENGOT. C. Aghajanian: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, Roche/Genentech, Blueprint Medicine; Financial Interests, Institutional, Research Grant: AbbVie, AstraZeneca, Clovis Oncology, Genentech; Financial Interests, Personal, Member of the Board of Directors: GOGFoundation, NRG Oncology. C. Mathews: Financial Interests, Institutional, Research Grant: Syros, Deciphera, Astellas Pharma, GSK/Tesaro, Seattle Genetics, EMD Serono, Merck, Regeneron, Moderna, AstraZeneca, Laekna. J. McNamara: Financial Interests, Institutional, Full or part-time Employment, Stocks: AstraZeneca. E. Lowe: Financial Interests, Institutional, Full or part-time Employment, Stocks: AstraZeneca. K.N. Moore: Financial Interests, Personal, Research Grant, Contracts for ovarian cancer investigator-initiated trials: Genentech/Roche, Lilly Pharmaceuticals, PTC Therapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Funding, Consulting fees: IMab; Financial Interests, Institutional, Funding, Payment for educational content: Onc Live, Physician Education Resource (PER), PRIME Oncology, Research to Practice; Financial Interests, Institutional, Advisory Board: Alkemeres, Aravive, Blueprint Pharmaceuticals, Eisai, Genentech/Roche, ImmunoGen, Mersana, Mereo, VBL Therapeutics; Financial Interests, Personal, Member, Participation on a data safety monitoring board: Incyte; Financial Interests, Institutional, Member, Associate Director: GOG partners; Financial Interests, Institutional, Member, Committee chair: NRG Ovarian Cancer. All other authors have declared no conflicts of interest.
518O - Overall survival results from ARIEL4: A phase III study assessing rucaparib vs chemotherapy in patients with advanced, relapsed ovarian carcinoma and a deleterious BRCA1/2 mutation
- Amit M. Oza (Toronto, Canada)
Abstract
Background
In the primary analysis of ARIEL4 (NCT02855944), rucaparib significantly improved progression-free survival (PFS) vs standard-of-care chemotherapy (CT) in patients (pts) with relapsed, heavily pretreated,
Methods
Pts were randomised 2:1 to oral rucaparib 600 mg BID or CT. In the CT group, pts with progression-free interval (PFI) ≥1 to <6 months (platinum resistant) or ≥6 to <12 months (partially platinum sensitive) received weekly paclitaxel; pts with PFI ≥12 months (fully platinum sensitive) received investigator’s choice of platinum-based CT (single-agent platinum or platinum doublet). Pts in the CT group could cross over to receive rucaparib upon confirmed radiographic progression per RECIST. OS was a standalone secondary endpoint; PFS2 was an exploratory endpoint.
Results
At data cutoff, 14/233 (6%) pts in the rucaparib group and 0/116 in the CT group were ongoing on assigned study treatment. Following progression on CT, 80 (69%) pts crossed over to receive rucaparib; overall, 313/349 (90%) pts received rucaparib from randomisation or after crossover. Death events have occurred in 244 (70%) pts. Efficacy endpoints are presented in the Table. Rucaparib safety was consistent with previous reports. HR, hazard ratio; NA, not analysed. *Data cutoff: 30 Sep 2020; †Data cutoff: 10 Apr 2022.
n PFS HR (95% CI)* PFS2 HR (95% CI)† Median OS, mo† OS HR (95% CI)† Rucaparib 233 0.665 (0.516–0.858); 0.860 (0.674–1.098) 19.4 1.313 (0.999–1.725) CT 116 25.4 Rucaparib 233 NA NA 19.4 0.423 (0.276–0.650) CT 36 9.1 Rucaparib 233 NA NA 19.4 1.059 (0.688–1.630) CT 116 26.2 Rucaparib 113 0.502 (0.343–0.733); 0.737 (0.512–1.060) 29.4 1.071 (0.709–1.618) CT 57 27.6 Rucaparib 120 0.821 (0.583–1.155); 0.968 (0.697–1.344) 14.2 1.511 (1.053–2.170) CT 59 22.2
Conclusions
PFS2 was not significantly different for pts in the rucaparib or CT groups. In the ITT population, the secondary endpoint of OS favoured CT. Amongst patients with platinum-sensitive disease, OS was similar between the treatment groups; the difference in the ITT population was driven by the platinum-resistant subgroup. OS was confounded by the high rate of crossover, raising important questions about the optimal sequencing of PARP inhibitors in advanced disease.
Clinical trial identification
NCT02855944 August 4, 2016.
Editorial acknowledgement
Medical writing and editorial support were funded by Clovis Oncology, Inc. and provided by Shelly Lim and Kathleen Blake of Ashfield MedComms, an Ashfield Health company.
Legal entity responsible for the study
Clovis Oncology, Inc.
Funding
Clovis Oncology, Inc.
Disclosure
A.M. Oza: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Clovis Oncology, Inc., GlaxoSmithKline. A.A. Fedenko: Financial Interests, Personal, Invited Speaker: MSD, Amgen; Financial Interests, Personal, Advisory Board: Novartis. A.C. de Melo: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Merck Sharp and Dohme, Novartis, Sanofi; Financial Interests, Institutional, Invited Speaker: Regeneron Pharmaceuticals, Novartis, Merck Sharp and Dohme, GlaxoSmithKline, F. Hoffmann-La Roche, Clovis Oncology, Inc., Bristol-Myers Squibb, AstraZeneca, Amgen. Y. Shparik: Financial Interests, Personal, Other, honoraria: AstraZeneca, Merck Sharp & Dohme; Financial Interests, Other, honoraria: Roche. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, ImmunoGen, Genmab, Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding accdemic trial: MSD, Clovis Oncology, PharmaMar; Financial Interests, Institutional, Funding, Grant for founding acamemic trial: GSK; Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Invited Speaker, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche; Non-Financial Interests, Member, Board of Directors: GCIG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. B. Maćkowiak-Matejczyk: Financial Interests, Personal, Invited Speaker, honoraria: AstraZeneca, GlaxoSmithKline, Roche; Financial Interests, Personal, Advisory Board: Seagen , GlaxoSmithKline; Financial Interests, Personal and Institutional, Funding: Clovis Oncology, Inc., AstraZeneca AB, AstraZeneca Pharma Poland sp zoo, MERSANA Therapeutics, MSD Polska Sp zoo, Parexel International Limited, Quiniles Eastern Holdings, Regeneron Pharmaceuticals, Roche Polska sp zoo, Seagen, Tesaro, Tesaro Bio Netherlands BV. D. Thomas: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K.K. LIN: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. K. McLachlan: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. S. Goble: Financial Interests, Personal, Full or part-time Employment: Clovis Oncology, Inc.; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Inc. R. Kristeleit: Financial Interests, Personal, Advisory Board: GSK, Eisai, Basilea Pharmaceutica, iTEOS, Clovis Oncology, Shattuck Labs, AstraZeneca, Regeneron; Financial Interests, Personal, Invited Speaker: GSK, Zydus Cadila, Clovis Oncology, AstraZeneca, GSK; Financial Interests, Personal, Expert Testimony: Amgen; Financial Interests, Personal, Other, Membert of Oncology and Haematology Expert Advisory Group: Commission on Human Medicines; Financial Interests, Institutional, Invited Speaker: GSK, Clovis Oncology, Clovis Oncology, Eisai, InCyte, AstraZeneca, MSD, Roche, BerGenBio, Allarity, IoVance, Artios, Regeneron; Financial Interests, Institutional, Research Grant: MSD. All other authors have declared no conflicts of interest.
Invited Discussant LBA29, 517O and 518O
- Jonathan A. Ledermann (London, United Kingdom)
Q&A
LBA30 - Phase III ATALANTE/ov29 trial: Atezolizumab (Atz) versus placebo with platinum-based chemotherapy (Cx) plus bevacizumab (bev) in patients (pts) with platinum-sensitive relapse (PSR) of epithelial ovarian cancer (OC)
- Jean Emmanuel Kurtz (Strasbourg, France)
Abstract
Background
Standard Cx for PSROC (> 6 months after last platinum dose) includes carboplatin plus pegylated liposomal doxorubicin (CbD) or gemcitabine (CbG) or paclitaxel (CbP) with or without bev. ATALANTE/ENGOT-ov29 (NCT02891824) is the first Phase III trial to evaluate Atz with Cx and bev for pts with PSROC.
Methods
Eligible pts had PSROC and ≤2 prior lines of Cx. Pts were randomised 2:1 to Atz (1200 mg, d1, q3w or 800 mg, d1&15, q4w with CbD up to 24 months [m]) or placebo (Pbo) with Cx at investigator-choice (CbD/CbG/CbP, 6 cycles) plus bev (15 mg/kg, d1, q3w or 10 mg/kg, d1&15, q4w), stratified by platinum-free interval, PD-L1 status on biopsy at study entry and Cx cohort. The co-primary endpoints are investigator-assessed progression-free survival (PFS) in the intent-to-treat (ITT) and PD-L1-positive (≥1% IC per tumour area) pts. Type I error was set at 0.025.
Results
From 10/2016 to 09/2019, 614 pts were randomized to Atz (n=410) or Pbo (n=204). Pts characteristics were balanced; Cx: CbD (63%), CbG (29%), CbP (8%), 1 (74%) or 2 (26%) prior lines, prior bev (62%). PD-L1 status was positive, negative, unknown in 38%, 49% and 13% of pts. Median follow-up was 36 m. The median PFS in the ITT pts was 13.5 and 11.2 m for the Atz and Pbo arms (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99;
Conclusions
The ATALANTE trial evaluating the addition of Atz to standard therapy of PSROC pts did not meet its PFS co-primary endpoints in the ITT and PD-L1-positive pts. Encouraging OS data warrant further analyses with longer follow-up. Further research on ATALANTE biopsy samples is warranted to better decipher the immunological landscape of PSROC.
Clinical trial identification
2015-005471-24.
Editorial acknowledgement
Jennifer Kelly, Medi-Kelsey Limited.
Legal entity responsible for the study
ARCAGY-GINECO.
Funding
F. Hoffmann - La Roche Ltd.
Disclosure
J.E. Kurtz: Financial Interests, Personal, Advisory Board: Tesaro, Merck Serono, Clovis, AstraZeneca, GSK; Financial Interests, Personal, Other, Travel expenditure: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Invited Speaker: Astra Zeneca, GSK, Bristol Myers Squib; Non-Financial Interests, Principal Investigator: Roche; Other, Immediate member family employed by Merck Sharp Dohme: Merck Sharp Dohme. E. Pujade-Lauraine: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, GSK; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, GSK; Financial Interests, Personal, Writing Engagements: Astra Zeneca, GSK; Financial Interests, Personal, Other, IDMC: INCYTE; Non-Financial Interests, Institutional, Full or part-time Employment: ARCAGY-GINECO; Non-Financial Interests, Institutional, Other, CEO: ARCAGY-Research. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, Immunogen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: AbbVie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, Immunogen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research ( via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). M.J. Rodrigues: Financial Interests, Personal, Invited Speaker: ASTRA ZENECA, GlaxoSmithKline, Merck Sharp and Dohme, Immunocore; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb, Merck Sharp and Dohme, Daiichi Sankyo; Non-Financial Interests, Invited Speaker: Société Française du Cancer. N. de Gregorio: Financial Interests, Personal, Other, Travel expenses: ASTRA ZENECA; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Myriad, GSK, MSD, Clovis, PharmaMar; Non-Financial Interests, Other: AGO Study group, Organkommission Ovar. J. Martinez-Garcia: Financial Interests, Personal, Advisory Board: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar; Financial Interests, Personal, Invited Speaker: Clovis Oncology, GSK-Tesaro, PharmaMar; Financial Interests, Personal, Other, Travel/accommodation/expenses for meeting: GSK-Tesaro, PharmaMar. P. Pautier: Financial Interests, Personal, Advisory Board, 2015, 2022: PharmaMar; Financial Interests, Institutional, Advisory Board, 2020: Roche, Clovis; Financial Interests, Institutional, Advisory Board, 2021: AstraZeneca; Financial Interests, Personal, Advisory Board, 2019-2020: AstraZeneca; Financial Interests, Institutional, Advisory Board: GSK; Financial Interests, Personal, Advisory Board, 2018-2019: Roche; Financial Interests, Institutional, Expert Testimony, 2022: MSD. M.A. Mouret Reynier: Financial Interests, Personal, Other, Board participations and symposiums: Pfizer, Roche, Myriad, Astra-Zeneca, MSD, Lilly, Novartis, Eisai; Financial Interests, Institutional, Other, Clinical Trials: BMS, AbbVie, Roche, Novartis, MSD, Astra-Zeneca. F. Selle: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK-Tesaro, MSD, Sandoz (Novartis), Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Roche, GSK-Tesaro, ASTRA ZENECA, Immunogen, MSD, Incyte, Agenus. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, ipsen, BMS, Bayer, Esai; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Astellas; Financial Interests, Institutional, Invited Speaker: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Other, Other, travel: MSD, GSK. E. Bultot Boissier: Financial Interests, Personal, Invited Speaker: AstraZeneca; Non-Financial Interests, Other, ESMO Member: ESMO. A. Floquet: Financial Interests, Personal, Other, Consultancy: GSK; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Clovis Oncology; Financial Interests, Invited Speaker, French coordinator - DUO Trial: AstraZeneca; Financial Interests, Invited Speaker, French coordinator- MIRASOL Trial: Immunogen. P. Heudel: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Seagen; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: AstraZeneca. F. Heitz: Financial Interests, Personal, Invited Speaker: Amedes, Clovis; Financial Interests, Personal, Advisory Board: AstraZeneca, NovoCure, PharmaMar, Roche; Financial Interests, Institutional, Other, Trial Chair: Newoncology. All other authors have declared no conflicts of interest.
LBA31 - Randomized phase III trial of maintenance chemotherapy with tegafur-uracil versus observation following concurrent chemoradiotherapy for locally advanced cervical cancer, GOTIC-002 LUFT trial
- Keiichi Fujiwara (Saitama, Japan)
Abstract
Background
Maintenance chemotherapy with oral tegafur-uracil (UFT) after surgery was shown to prolong survival in lung, breast, gastric and colon cancer. Aim of this trial is to elucidate the efficacy of maintenance chemotherapy using UFT following concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer.
Methods
Eligible patients (pts) are those with FIGO (2008) stage Ib2 -IVa cervical cancer, who have squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma. Pts must have completed curative treatment of CCRT with a response of CR or PR. Pts were randomized to observation only (Arm O) or UFT maintenance cohort (Arm UFT) with 1:1 ratio. Dose of oral UFT was 400 mg /day for pts with body surface area (BSA)≥ 1.25 m2 and 300 mg/day for pts with BSA < 1.25 m2. Pts received UFT for 2 years without interruption unless disease progression or unacceptable toxicities happened. Primary endpoint was PFS and secondary endpoints included OS, safety and QOL. Significant level was 0.05 (one-side).
Results
Enrollment started in 2010 and completed in 2018. A total of 351 pts from 55 institutions in Japan were randomized either to Arm O (178 pts) or Arm UFT (173 pts). Safety data was analyzed in 176 pts in Arm O and 168 pts in Arm UFT. Pts characteristics were well balanced between two arms. Most of pts were stage IIb or IIIb, and received CCRT using weekly cisplatin. Median PFS did not reach for both arms. Five-year PFS rates were 61.3% (90%CI: 54.8-67.1) for Arm O and 62.0% (90%CI: 55.4-67.8) for Arm UFT (p=0.634). Hazard ratio (HR) of PFS for Arm UFT vs. Arm O was 0.92 (90%CI: 0.69-1.22). Five-year OS rates were 77.6% (90%CI: 71.8-82.4) for Arm O and 76.1% (90%CI: 70.1-81.1) for Arm UFT (p=0.869). HR of OS for Arm UFT vs. Arm O was 1.04 (90%CI: 0.73-1.47). All grade adverse events (AEs) occurred significantly more in Arm UFT (93.5%) than Arm O (73.9%) (Odds ratio = 5.05, 95%CI: 2.51, 10.15) but most of them were grade 1 or 2. Incidence of AEs ≥ grade 3 were 15.9% in Arm O and 22.6% in Arm UFT.
Conclusions
Maintenance chemotherapy using UFT for 2 years after definitive chemoradiation therapy for locally advanced cervical cancer was well tolerated. However, it did not improve either PFS or OS.
Clinical trial identification
jRCTs031180174.
Legal entity responsible for the study
Gynecologic Oncology Trial and Investigation Consortium (GOTIC).
Funding
Taiho Pharmaceutical CO., Ltd.
Disclosure
K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda, Regenerone, Zeria; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai. All other authors have declared no conflicts of interest.
Invited Discussant LBA30 and LBA31
- Mansoor Raza Mirza (Copenhagen, Denmark)
Q&A
- All Speakers (Lugano, Switzerland)