Clinical trialPhase 3Ovarian cancer

Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer

N Engl J Med · 2018391 patients

Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, et al. N Engl J Med. 2018. 379:2495-2505

A newer report of this study has been published: 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 (2023)

Study type: Clinical trial
Study name: SOLO-1 (GOG 3004)
Phase: Phase 3
Design: Randomised, double-blind, international, placebo-controlled trial (2:1 ratio)
Sample size: 391 patients
Source: N Engl J Med · 2018
Trial registration: NCT01844986

In plain words

In women with advanced ovarian cancer and a BRCA gene mutation, taking olaparib tablets for two years after finishing chemotherapy greatly reduced the chance of the disease coming back. After seven years, 67% of women in the olaparib group were alive (compared with 46.5%), and almost half of them had not yet needed any further treatment; this means that for some patients there is a real chance of long-term remission.

Key results

HR 0.30

Risk of progression or death

95% CI 0.23–0.41; P<0.001; median follow-up 41 months

60% vs 27%

Free of progression at 3 years

Kaplan–Meier estimate

67.0% vs 46.5%

Alive at 7 years

Overall survival HR 0.55 (95% CI 0.40–0.76); P=0.0004 (the prespecified significance threshold of P<0.0001 was not met); JCO 2023

45.3% vs 20.6%

Alive and without subsequent therapy at 7 years

JCO 2023

Drugs in this study:Olaparib (Lynparza)

Dose and schedule cards

Olaparib maintenance (SOLO-1)

BRCA mutation (germline or somatic), advanced disease, with complete or partial response to first-line platinum-based chemotherapyCycle length: ContinuousOn the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

BRCA mutation (germline or somatic), advanced disease, with complete or partial response to first-line platinum-based chemotherapy

Drug	Dose	Route	Schedule
Olaparib	300 mg twice daily (tablets)	Oral	Continuously

Cycle length: Continuous
Duration: Until progression, unacceptable toxicity or 2 years; complete response at 2 years: stop; residual disease at 2 years: continuation at the physician’s discretion

Dose modification: 250 mg, then 200 mg twice daily; CrCl 31 to 50 mL/min: 200 mg twice daily; avoid strong or moderate CYP3A inhibitors (if unavoidable, 100 or 150 mg twice daily). Monitoring: start after haematologic toxicity from chemotherapy has recovered to grade 1 or lower; complete blood count at baseline and monthly; prolonged cytopenia: evaluate for MDS/AML.

On the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

First-line maintenance in BRCA-mutated advanced ovarian cancer (SOLO-1)

Ovarian, fallopian tube or primary peritoneal cancer; complete or partial response to first-line platinum chemotherapy; germline or somatic BRCACycle length: ContinuousOn the page “Olaparib (Lynparza)” · Standard dosing (FDA label)

Ovarian, fallopian tube or primary peritoneal cancer; complete or partial response to first-line platinum chemotherapy; germline or somatic BRCA

Drug	Dose	Route	Schedule
Continuous
Olaparib	300 mg	Oral (with or without food)	Twice daily (about every 12 hours)

Cycle length: Continuous
Duration: Until progression, unacceptable toxicity or completion of 2 years; stop at 2 years with a complete response; with residual disease, continuing beyond 2 years at the physician's discretion

On the page “Olaparib (Lynparza)” · Standard dosing (FDA label)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Olaparib (260 patients)

Olaparib tablets 300 mg twice daily, orally, continuously; started within 8 weeks of the last chemotherapy dose. Treatment continued for up to 2 years or until radiological progression (modified RECIST 1.1); patients with no evidence of disease at 2 years stopped treatment, and patients with evidence of disease could continue in a blinded manner. Crossover between arms was not allowed.

2Placebo (131 patients)

Placebo tablets twice daily with the same schedule and discontinuation rules.

Source of the regimen details: Abstract of the paper (300 mg tablets twice daily) and full text of the 7-year analysis, JCO 2023 (PMC9870219; start within 8 weeks, maximum 2 years and discontinuation rules)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with newly diagnosed advanced (FIGO stage III or IV) ovarian, primary peritoneal or fallopian tube cancer of high-grade serous or endometrioid histology, with a BRCA1 and/or BRCA2 mutation (388 with a germline mutation and 2 with a centrally confirmed somatic mutation), who had a complete or partial clinical response after platinum-based chemotherapy.

Endpoints

Primary outcome: progression-free survival (investigator-assessed). Secondary: overall survival (prespecified descriptive analysis after 7 years), time to subsequent therapy, safety.

Safety and side effects

Adverse events were consistent with the known toxicity of olaparib. At 7-year follow-up, the most common adverse events were nausea, fatigue/asthenia, vomiting and anaemia, and anaemia was the most common grade 3 or higher event. Serious adverse events occurred in 21.2% of the olaparib group and 13.8% of the placebo group. Myelodysplastic syndrome/acute myeloid leukaemia was reported in 4 patients (1.5%) in the olaparib group and 1 patient (0.8%) in the placebo group.

Clinical significance and place in guidelines

SOLO-1 established first-line maintenance therapy with a PARP inhibitor. The FDA approved olaparib in December 2018 for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer. The 7-year analysis (DiSilvestro et al., JCO 2023) showed a clinically meaningful improvement in overall survival (although it was not declared significant under the prespecified statistical criterion). The ESMO guideline (and the 2025 Pan-Asian version) recommends 2 years of olaparib for BRCA1/2-mutated tumours at level [I, A]. BRCA testing is recommended for all patients with high-grade non-mucinous ovarian cancer at diagnosis.

Limitations

Only patients with a BRCA mutation were enrolled; overall survival was a secondary outcome and its analysis was descriptive; patients without a response to platinum were not enrolled.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.