Clinical trialPhase 3Ovarian cancer

Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial

The Lancet Oncology · 2017295 patients (196 in the olaparib group and 99 in the placebo group)

Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, et al. The Lancet Oncology. 2017. 18:1274-1284

Study type: Clinical trial
Study name: SOLO2/ENGOT-Ov21
Phase: Phase 3
Design: International, multicentre, randomised, double-blind, placebo-controlled trial
Sample size: 295 patients (196 in the olaparib group and 99 in the placebo group)
Source: The Lancet Oncology · 2017
Trial registration: NCT01874353

In plain words

In this study, women with ovarian cancer that had come back, who had responded to platinum-containing chemotherapy and had a BRCA1 or BRCA2 gene mutation, were given olaparib tablets or placebo (dummy) tablets after finishing chemotherapy. The median time until the disease grew again was about 19.1 months with olaparib, compared with 5.5 months with placebo. Quality of life did not get worse with this drug. The most common important side effect was anaemia (low red blood cells), and other side effects were mostly mild and manageable.

Key results

19.1 months (95% CI 16.3 to 25.7) vs 5.5 months (5.2 to 5.8)

Median progression-free survival (investigator-assessed)

HR 0.30 (95% CI 0.22 to 0.41); P<0.0001

19% (38 of 195 patients) vs 2% (2 of 99 patients)

Grade ≥3 anaemia

Olaparib vs placebo

18% (35 patients) vs 8% (8 patients)

Serious adverse events

Olaparib vs placebo

Drugs in this study:Olaparib (Lynparza)

Dose and schedule cards

PARP inhibitor maintenance after response to platinum at recurrence (SOLO2)

Platinum-sensitive recurrence with complete or partial response to platinum-based chemotherapy; olaparib: germline or somatic BRCA mutation; niraparib: germline BRCA mutationCycle length: ContinuousOn the page “Ovarian cancer” · Platinum-sensitive recurrence

Platinum-sensitive recurrence with complete or partial response to platinum-based chemotherapy; olaparib: germline or somatic BRCA mutation; niraparib: germline BRCA mutation

Drug	Dose	Route	Schedule
One of the two
Olaparib	300 mg twice daily	Oral	Continuously
Niraparib	300 mg once daily	Oral	Continuously; start no later than 8 weeks after the last platinum dose

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

Monitoring and dose modification as in the first-line olaparib and niraparib rows. ESMO: continue the PARP inhibitor until progression or the start of the next treatment [I, A].

On the page “Ovarian cancer” · Platinum-sensitive recurrence

Maintenance in BRCA-mutated recurrent ovarian cancer (SOLO-2)

Complete or partial response to platinum chemotherapy; germline or somatic BRCACycle length: ContinuousOn the page “Olaparib (Lynparza)” · Standard dosing (FDA label)

Complete or partial response to 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 or unacceptable toxicity

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 group

Olaparib tablets 300 mg (two 150 mg tablets) twice daily, orally, as maintenance until radiological progression (RECIST, investigator-assessed) or for as long as the investigator judged it beneficial; dose reduction to 250 mg and then 200 mg twice daily was allowed. 196 patients were randomised (one patient was randomised in error and was not treated).

2Placebo group

Matching placebo tablets twice daily on the same schedule (99 patients).

Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT01874353 (treatment duration and dose reduction)

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 aged 18 years and older with relapsed, platinum-sensitive ovarian cancer with a BRCA1 or BRCA2 mutation who had received at least two prior lines of chemotherapy. Baseline ECOG performance status was 0 to 1, and the disease was histologically confirmed as high-grade serous or high-grade endometrioid cancer (including primary peritoneal or fallopian tube cancer).

Endpoints

Primary endpoint: investigator-assessed progression-free survival (PFS). Efficacy analyses were in the intention-to-treat (ITT) population and safety analyses in patients who received at least one dose of study treatment. Randomisation was 2:1, stratified by response to previous platinum-based chemotherapy (complete versus partial) and length of the platinum-free interval (6 to 12 months versus ≥12 months).

Safety and side effects

The most common grade 3 or higher adverse events: anaemia (38 [19%] of 195 patients in the olaparib group versus 2 [2%] of 99 in the placebo group), fatigue or asthenia (8 [4%] versus 2 [2%]) and neutropenia (10 [5%] versus 4 [4%]).

Serious adverse events occurred in 35 patients (18%) in the olaparib group and 8 patients (8%) in the placebo group. The most common were anaemia (7 patients, 4%), abdominal pain (3 patients, 2%) and intestinal obstruction (3 patients, 2%) in the olaparib group, and constipation (2 patients, 2%) and intestinal obstruction (2 patients, 2%) in the placebo group. One patient (1%) in the olaparib group had a treatment-related adverse event (acute myeloid leukaemia) with a fatal outcome.

Clinical significance and place in guidelines

This trial showed that maintenance therapy with olaparib tablets in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation significantly improves progression-free survival, without a detrimental effect on quality of life. Anaemia was the most important high-grade adverse event. Regulatory approval status and current guideline recommendations should be checked separately, as they are not mentioned in the abstract.

Limitations

The primary endpoint was investigator-assessed. This report is the primary analysis of an ongoing study, and overall survival results are not reported in the abstract. The results apply only to patients with BRCA1/2 mutations and platinum-sensitive high-grade serous or high-grade endometrioid cancer. The study was funded by AstraZeneca.

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.