LYNPARZA (olaparib)

LynparzaTM (olaparib) is a first‐in‐class PARP inhibitor (PARPi) that allows women with BRCA mutated (BRCAm) platinum‐sensitive relapsed high-grade serous ovarian cancer to extend progression‐free survival (PFS).1-3

About Study 19

BRCAm Sub-analysis

Patients with BRCAm platinum-sensitive relapsed ovarian cancer experience the greatest clinical benefit with Lynparza.2,3

A pre-planned subgroup retrospective analysis by BRCAm status identified patients with BRCAm ovarian cancer (n=136, 51%) as the subgroup that derived the greatest clinical benefit from Lynparza maintenance monotherapy.3

Retrospective analysis by BRCAm status identified patients with BRCAm ovarian cancer
Retrospective analysis by BRCAm status identified patients with BRCAm ovarian cancer

Adapted with permission from Ledermann.2

Patient Characteristics

Study 19 included BRCAm patients from various age groups and ECOG§§ performance status levels.3

BRCam patients from various age groups
BRCam patients from various age groups

Adapted with permission from Ledermann.3  

*ECOG: Eastern Cooperative Oncology Group.

§§Ancestry was self-reported.

  • Eligible patients were aged 18 years or older and had recurrent ovarian or fallopian tube cancer, or primary peritoneal cancer, with high-grade (grade 2 or 3) serous features or a serous component, which was platinum-sensitive (defined as no disease progression in the first 6 months after the last dose of the penultimate line of platinum-based chemotherapy).2
  • Patients entering the study had received two or more previous courses of platinum-based chemotherapy and were required to have shown an objective response (complete or partial response) according to Response Evaluation Criteria In Solid Tumors (RECIST) or Gynaecologic Cancer Intergroup criteria.2
Objective response to most recent platinum-based regimen
Objective response to most recent platinum-based regimen

Adapted with permission from Ledermann.3

Efficacy

Adding Lynparza to the treatment paradigm allows women living with BRCAm platinum-sensitive relapsed high-grade serous ovarian cancer to actively extend PFS.3

PFS

+6.9 MONTH IMPROVEMENT IN MEDIAN PFS OVER PLACEBO3

Maintenance treatment with Lynparza has demonstrated a significant benefit for BRCAm platinum-sensitive relapsed high-grade serous ovarian cancer patients, improving PFS by a median of 6.9 months vs placebo (HR 0.18; 95% CI 0.10-0.31; p<0.00001; median PFS 11.2 vs 4.3 months).3, 4

A comparison chart between Placebo and Lynparza
A comparison chart between Placebo and Lynparza

Adapted with permission.3

82% reduction in the risk of disease progression or death compared to placebo. (HR 0.18; 95% CI 0.10-0.31; p<0.00001; median PFS 11.2 vs 4.3 months).3, 4

A comparison chart between Placebo and Lynparza
A comparison chart between Placebo and Lynparza

Adapted with permission.3

TFST

Lynparza treatment compared to placebo
Lynparza treatment compared to placebo

For patients with BRCA mutation, Lynparza delays the need for subsequent treatment.4, 35

In patients with a BRCA mutation, Lynparza delayed the time from randomisation to start of first subsequent therapy or death (TFST)††, or when patients needed their next chemotherapy, by a median of 9.4 months (HR 0.32; 95% CI 0.22-0.48; p<0.0001; median 15.6 months vs 6.2 months).35

A comparison chart between Placebo and Lynparza about TSFT
A comparison chart between Placebo and Lynparza about TSFT

Adapted with permission from Ledermann.35

††An exploratory retrospective analysis.

TSST

A comparison chart between Placebo and Lynparza about TSST
A comparison chart between Placebo and Lynparza about TSST

In patients with a BRCA mutation, the time from randomisation to start of second subsequent therapy or death (TSST)‡‡ was 6.7 months longer for Lynparza treated patients vs placebo (HR 0.41; 95% CI 0.28-0.62; p<0.0001; median 22.0 months vs 15.3 months).35

‡‡An exploratory retrospective analysis.

Overall Survival(OS)

Overall survival was assessed as a secondary objective.3

  • There was no statistically significant difference in OS between the two arms in the BRCAm population.35
  • In the BRCAm population there was a numerical difference of a median of 4.7 months in favour of Lynparza (HR 0.62; 95% CI 0.41-0.94; p=0.025; median 34.9 months Lynparza vs 30.2 months placebo).35
A comparison chart between Placebo and Lynparza about OS
A comparison chart between Placebo and Lynparza about OS

Adapted with permission from Ledermann.35

Long term exposure to treatment

15% of patients with a BRCA mutation remain on Lynparza at 5 years vs. 2% of patients on placebo supporting the long-term benefit and tolerability of this treatment.35

At 5 years, 15% of patients with a BRCAm were still taking Lynparza
At 5 years, 15% of patients with a BRCAm were still taking Lynparza

Quality of Life (QOL)

Quality of Life (QOL) was similar whether patients were on Lynparza or placebo.3,4

No statistically significant differences were observed between Lynparza and placebo in patient reported symptoms or health-related quality of life (HRQoL) as measured by improvement and worsening rates in the FACT/NCCN ovarian symptom index (FOSI), trial outcome index (TOI) and functional analysis of cancer therapy–ovarian total score (FACT-O total). 3,4

Quality of life was similar whether patients were on Lynparza or placebo.
Quality of life was similar whether patients were on Lynparza or placebo.

Safety and Tolerability

The safety and tolerability of Lynparza are acceptable for oral maintenance treatment administration.4

The most common adverse events associated with Lynparza monotherapy for patients identified with BRCAm were nausea, fatigue and vomiting and were generally mild to moderate (grade 1 or 2) in severity.4 The most common Grade 3 and 4 adverse events reported for Lynparza vs placebo were fatigue (7% vs 2%) and anaemia (5% vs 2%), neutropenia (4% vs 2%) and vomiting (3% vs 0%).3, 4

Adverse events
Adverse events

Study Overview

Study 19 was a randomised, double-blind, placebo-controlled phase II clinical trial.2

In Study 19, Lynparza as maintenance treatment met the primary endpoint of improving PFS in the overall study population.2

Lynparza as maintenance treatment met the primary endpoint of improving PFS in the overall study population.
Lynparza as maintenance treatment met the primary endpoint of improving PFS in the overall study population.

A retrospective analysis was conducted on a pre-defined subgroup of patients with BRCA mutations. This is included 51% of patients N=136.3

**Platinum-sensitive defined by a relapse-free period of ~6 months following a response to the final dose of platinum-based chemotherapy treatment.