Overall Survival With Maintenance Olaparib at a 7-Year Follow-Up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial

Abstract

Purpose: In SOLO1/GOG 3004 (ClinicalTrials.gov identifier: NCT01844986), maintenance therapy with the poly(ADP-ribose) polymerase inhibitor olaparib provided a sustained progression-free survival benefit in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation. We report overall survival (OS) after a 7-year follow-up, a clinically relevant time point and the longest follow-up for any poly(ADP-ribose) polymerase inhibitor in the first-line setting.

Methods: This double-blind phase III trial randomly assigned patients with newly diagnosed advanced ovarian cancer and a BRCA mutation in clinical response to platinum-based chemotherapy to maintenance olaparib (n = 260) or placebo (n = 131) for up to 2 years. A prespecified descriptive analysis of OS, a secondary end point, was conducted after a 7-year follow-up.

Results: The median duration of treatment was 24.6 months with olaparib and 13.9 months with placebo, and the median follow-up was 88.9 and 87.4 months, respectively. The hazard ratio for OS was 0.55 (95% CI, 0.40 to 0.76; P = .0004 [P < .0001 required to declare statistical significance]). At 7 years, 67.0% of olaparib patients versus 46.5% of placebo patients were alive, and 45.3% versus 20.6%, respectively, were alive and had not received a first subsequent treatment (Kaplan-Meier estimates). The incidence of myelodysplastic syndrome and acute myeloid leukemia remained low, and new primary malignancies remained balanced between treatment groups.

Conclusion: Results indicate a clinically meaningful, albeit not statistically significant according to prespecified criteria, improvement in OS with maintenance olaparib in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation and support the use of maintenance olaparib to achieve long-term remission in this setting; the potential for cure may also be enhanced. No new safety signals were observed during long-term follow-up.

Conflict of interest statement

Paul DiSilvestro

Consulting or Advisory Role: AstraZeneca, GlaxoSmithKline/Tesaro

Research Funding: Janssen Oncology (Inst), Tesaro (Inst), AstraZeneca (Inst), Genentech (Inst), AbbVie (Inst)

Susana Banerjee

Honoraria: AstraZeneca, GlaxoSmithKline, Clovis Oncology, Pfizer, Immunogen, MSD Oncology, Mersana, Roche, Takeda, Amgen

Consulting or Advisory Role: Amgen, GlaxoSmithKline, MSD Oncology, Mersana, AstraZeneca, Seattle Genetics, OncXerna Therapeutics, Shattuck Labs, Merck Serono, Immunogen

Research Funding: GlaxoSmithKline (Inst), AstraZeneca (Inst)

Nicoletta Colombo

Employment: Sarepta Therapeutics (I)

Honoraria: Roche/Genentech, AstraZeneca, Tesaro, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Pfizer, Mersana, Eisai, Advaxis, Nuvation Bio

Consulting or Advisory Role: Roche/Genentech, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Tesaro, GlaxoSmithKline, Immunogen, Pfizer, Mersana, Eisai, Advaxis, Nuvation Bio

Giovanni Scambia

Consulting or Advisory Role: Clovis Oncology, AstraZeneca, PharmaMar, Roche, Tesaro

Speakers' Bureau: Clovis Oncology, MSD

Ana Oaknin

Consulting or Advisory Role: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Immunogen, Genmab, Mersana, GSK, Deciphera, AGENUS, Corcept Therapeutics, Eisai, EMD Serono, F. Hoffmann-La Roche, Medison, Merck Sharp & Dohme, Novocure, prIME Oncology, Shattuck Labs, Sutro Biopharma, ITeos Therapeutics, Amgen

Research Funding: AbbVie (Inst), Ability Pharmaceuticals (Inst), Advaxis (Inst), Aeterna Zentaris (Inst), Aprea Therapeutics (Inst), Clovis Oncology Inc (Inst), Eisai (Inst), Roche (Inst), Regeneron (Inst), Agenus (Inst), AstraZeneca (Inst), BeiGene (Inst), Belgian Gynaecological Oncology Group (BGOG) (Inst), Bristol Myers Squibb International Corporation (BMS) (Inst), Corcept Therapeutics (Inst), Immunogen (Inst), Iovance Biotherapeutics (Inst), Lilly (Inst), Medimmune (Inst), Merck (Inst), Merck Sharp & Dohme (Inst), Mundipharma Research (Inst), /Inst), Seagen (Inst), Seattle Genetics (Inst), Sutro Biopharma (Inst), Tesaro (Inst), Verastem (Inst)

Travel, Accommodations, Expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche

Michael Friedlander

Honoraria: AstraZeneca, MSD, Lilly, Takeda, Novartis, GlaxoSmithKline

Consulting or Advisory Role: AstraZeneca, MSD, AbbVie, Lilly, Takeda, Novartis, GlaxoSmithKline, Eisai, Incyclix

Speakers' Bureau: AstraZeneca, ACT Genomics, GlaxoSmithKline

Research Funding: BeiGene (Inst), AstraZeneca (Inst), Novartis (Inst)

Travel, Accommodations, Expenses: AstraZeneca

Alla Lisyanskaya

Honoraria: Incuron (Inst), MSD (Inst), AstraZeneca (Inst), Regeneron (Inst), Roche (Inst)

Research Funding: Incuron, Roche, AstraZeneca, Regeneron, MSD

Anne Floquet

Honoraria: GlaxoSmithKline

Travel, Accommodations, Expenses: GlaxoSmithKline, PharmaMar, AstraZeneca

Alexandra Leary

Honoraria: Medscape

Consulting or Advisory Role: Clovis Oncology (Inst), AstraZeneca (Inst), Tesaro (Inst), MSD (Inst), GlaxoSmithKline (Inst), Merck Serono (Inst), Zentalis, PEGASCY, Blueprint Medicines (Inst)

Research Funding: Inivata (Inst), Sanofi (Inst)

Travel, Accommodations, Expenses: AstraZeneca, Tesaro

Gabe S. Sonke

Consulting or Advisory Role: Novartis (Inst), Seattle Genetics (Inst), Biovica (Inst)

Research Funding: Merck Sharp & Dohme (Inst), Agendia (Inst), AstraZeneca/Merck (Inst), Roche (Inst), Novartis (Inst)

Charlie Gourley

Honoraria: AstraZeneca, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Takeda

Consulting or Advisory Role: AstraZeneca, Cor2Ed, GlaxoSmithKline, MSD Oncology, Clovis Oncology

Research Funding: AstraZeneca (Inst), GlaxoSmithKline (Inst), MSD Oncology (Inst), Novartis (Inst), BerGenBio (Inst), MedAnnex (Inst)

Patents, Royalties, Other Intellectual Property: One patent issued and four pending for a gene expression signature to predict cancer sensitivity to antiangiogenic therapy (Inst)

Expert Testimony: Amgen

Amit Oza

Uncompensated Relationships: Ozmosis Research

Antonio González-Martín

Consulting or Advisory Role: Roche, Tesaro/GSK, Clovis Oncology, AstraZeneca, MSD, Genmab, Immunogen, Oncoinvent, Pfizer/EMD Serono, Amgen, Mersana, SOTIO, Sutro Biopharma, MacroGenics, Novartis, Alkermes, Hedera Dx, Novocure, Seattle Genetics, Takeda

Speakers' Bureau: Roche, AstraZeneca, Tesaro/GSK, PharmaMar, Clovis Oncology, MSD Oncology

Research Funding: Roche (Inst), Tesaro/GSK (Inst)

Travel, Accommodations, Expenses: Roche, AstraZeneca, PharmaMar, Tesaro/GSK, MSD Oncology

Carol Aghajanian

Consulting or Advisory Role: Eisai, AstraZeneca/Merck, Roche/Genentech, Repare Therapeutics

Research Funding: Genentech/Roche (Inst), AbbVie (Inst), Clovis Oncology (Inst), AstraZeneca (Inst)

William Bradley

Consulting or Advisory Role: Celsion, Inovio Pharmaceuticals

Travel, Accommodations, Expenses: Inovio Pharmaceuticals, Clovis Oncology

Cara Mathews

Research Funding: AstraZeneca (Inst), Tesaro/GSK (Inst), Syros Pharmaceuticals (Inst), Astellas Pharma (Inst), Seattle Genetics (Inst), Deciphera (Inst), Moderna Therapeutics (Inst), Regeneron (Inst), Roche/Genentech (Inst), Pfizer (Inst), Laekna Therapeutics (Inst), EMD Serono (Inst), Merck (Inst)

Joyce Liu

Consulting or Advisory Role: Clovis Oncology, Genentech/Roche, GlaxoSmithKline, Regeneron, AstraZeneca, Eisai

Research Funding: Genentech/Roche (Inst), AstraZeneca (Inst), Boston Biomedical (Inst), Acetylon Pharmaceuticals (Inst), Bristol Myers Squibb (Inst), Agenus (Inst), CytomX Therapeutics (Inst), Regeneron (Inst), Tesaro (Inst), Clovis Oncology (Inst), Surface Oncology (Inst), 2× Oncology (Inst), Vigeo Therapeutics (Inst), Aravive (Inst), Arch Oncology (Inst), Zentalis (Inst)

Uncompensated Relationships: Merck

John McNamara

Employment: AstraZeneca

Stock and Other Ownership Interests: AstraZeneca

Consulting or Advisory Role: AstraZeneca

Travel, Accommodations, Expenses: AstraZeneca

Elizabeth S. Lowe

Employment: AstraZeneca

Stock and Other Ownership Interests: AstraZeneca

Mei-Lin Ah-See

Employment: AstraZeneca

Stock and Other Ownership Interests: AstraZeneca

Consulting or Advisory Role: AstraZeneca (I), Bard1 Bioscience (I)

Research Funding: GRAIL (I), Johnson and Johnson (I)

Patents, Royalties, Other Intellectual Property: Progression of precancerous lesion predictor (I)

Kathleen N. Moore

Leadership: GOG Partners, NRG Oncology (Inst)

Honoraria: Research To Practice, Prime Oncology, Physicians' Education Resource, Great Debates and Updates

Consulting or Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, VBL Therapeutics, Merck, Aravive, Eisai, Mersana (Inst), Myriad Genetics, Alkermes (Inst), Blueprint Pharmaceuticals (Inst), GlaxoSmithKline/Tesaro (Inst), I-Mab (Inst), InxMed (Inst), Mereo BioPharma (Inst), OncXerna Therapeutics, Onconova Therapeutics, Mereo BioPharma, Novartis

Research Funding: PTC Therapeutics (Inst), Lilly (Inst), Merck (Inst), Tesaro (Inst), Genentech (Inst), Clovis Oncology (Inst), Lilly Foundation (Inst), Regeneron (Inst), Advaxis (Inst), Bristol Myers Squibb (Inst), Verastem (Inst), Novartis Pharmaceuticals UK Ltd (Inst), AstraZeneca (Inst), Agenus (Inst), Takeda (Inst), Forty Seven (Inst), Stem CentRx (Inst), Immunogen (Inst), Bayer (Inst), Novogen (Inst), AbbVie/Stemcentrx (Inst), Artios (Inst), Bolt Biotherapeutics (Inst), Amgen (Inst), Daiichi Sankyo/Lilly (Inst), Cyteir (Inst), Immunocore (Inst)

Patents, Royalties, Other Intellectual Property: UpToDate

Other Relationship: GOG Partners (Inst)

No other potential conflicts of interest were reported.

Figures

FIG 1.

CONSORT diagram of patients. AE, adverse event; DCO, data cutoff.

FIG 2.

Kaplan-Meier estimates of OS. HR, hazard ratio; NR, not reached; OS, overall survival.

FIG 3.

Kaplan-Meier estimates of (A) TFST and (B) TSST. HR, hazard ratio; TFST, time to first subsequent therapy or death; TSST, time to second subsequent therapy or death.