Clinical trialPhase 3Ovarian cancer

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

JCO · 2023391 patients (260 in the olaparib group and 131 in the placebo group)

DiSilvestro P, Banerjee S, Colombo N, Scambia G, Kim BG, Oaknin A, et al. JCO. 2023. 41:609-617

Study type: Clinical trial
Study name: SOLO1/GOG 3004
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled phase 3 trial; prespecified descriptive analysis of overall survival after 7 years of follow-up
Sample size: 391 patients (260 in the olaparib group and 131 in the placebo group)
Source: JCO · 2023
Trial registration: NCT01844986

In plain words

In this study, women with advanced ovarian cancer and a BRCA gene mutation who had responded well to chemotherapy received olaparib or a placebo (dummy pill) for up to 2 years. After about 7 years of follow-up, 67% of patients in the olaparib group were alive compared with 46.5% in the placebo group. The difference in survival was clinically striking, although under the statistical rule set in advance it was not declared "significant". No new safety problems were seen during the long follow-up.

Key results

0.55 (95% CI 0.40 to 0.76)

Hazard ratio for overall survival

P = 0.0004 (P < 0.0001 was required to declare statistical significance)

67.0% vs 46.5%

Alive at 7 years (Kaplan–Meier estimate)

Olaparib vs placebo

45.3% vs 20.6%

Alive and without first subsequent therapy at 7 years

Kaplan–Meier estimate

24.6 months vs 13.9 months

Median treatment duration

Olaparib vs placebo

88.9 months vs 87.4 months

Median follow-up

Olaparib vs placebo

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

1Maintenance olaparib (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.

Median treatment duration 24.6 months; 10.0% of patients continued treatment beyond 2 years.

2Placebo (131 patients)

Placebo tablets twice daily with the same schedule and discontinuation rules. Median treatment duration 13.9 months.

Source of the regimen details: Full text of the paper (JCO 2023, open access PMC9870219, Treatment section) and the abstract of the original NEJM 2018 paper (300 mg twice daily)

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 ovarian, primary peritoneal or fallopian tube cancer (FIGO stage III or IV, high-grade serous or endometrioid) with a BRCA1 and/or BRCA2 mutation who had a complete or partial clinical response after platinum-based chemotherapy; randomisation (2:1) within 8 weeks of the last chemotherapy dose, stratified by clinical response (complete or partial).

Endpoints

The endpoint examined in this report was overall survival (OS), a secondary endpoint, assessed in a prespecified descriptive analysis after 7 years of follow-up. The percentage of patients alive and without first subsequent therapy was also reported.

Safety and side effects

The safety profile at 7-year follow-up was consistent with previous reports: the most common adverse events were nausea, fatigue/asthenia, vomiting and anaemia; 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 (most common: anaemia 7.3% versus 0% and neutropenia 1.5% versus 0%). Overall, MDS/AML was reported in 4 patients (1.5%) in the olaparib group and 1 patient (0.8%) in the placebo group, and new primary malignancies in 14 patients (5.4%) versus 8 patients (6.2%). Adverse events were usually managed with dose interruption or reduction.

Clinical significance and place in guidelines

This analysis shows that maintenance olaparib in newly diagnosed BRCA-mutated advanced ovarian cancer is associated with a clinically meaningful improvement in overall survival and supports its use to achieve long-term remission. Because the overall survival difference was not statistically significant under the prespecified criterion, this finding should be interpreted with care. Approval status and current guideline recommendations should be checked separately.

Limitations

Overall survival was a secondary endpoint and its analysis was descriptive. The P value (0.0004) did not reach the prespecified threshold for statistical significance (below 0.0001). Detailed data on grade ≥3 adverse events are not given in the abstract.

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.