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REVIEW IMPORTANT SAFETY INFORMATION BELOW.
Survival matters to them
Choose a PARPi with clinically meaningful PFS and OS* in HRD-positive†‡ aOC1 after response to 1L platinum-based chemotherapy
*Results for PFS and OS may vary.
mPFS
3.1 YEARS
Primary endpoint
Progression-free survival:
HR=0.33 (95% CI: 0.25–0.45)
3.1 years (37.2 months) median PFS with LYNPARZA + bevacizumab and ~1.5 years (17.7 months) with bevacizumab + placebo
mOS
~6.3 YEARS
Key secondary endpoint
Overall survival:
HR=0.62 (95% CI: 0.45–0.85)
~6.3 years (75.2 months) median OS with LYNPARZA + bevacizumab and ~4.8 years (57.3 months) with bevacizumab + placebo
See 5-year PFS results
Data based upon a prespecified exploratory subgroup analysis, which was not controlled for Type 1 error. HRD status was not a stratification factor in PAOLA-1.
Not an actual patient.
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SEE THE STUDY DESIGN AND ADDITIONAL EFFICACY DATA, AND REVIEW IMPORTANT SAFETY INFORMATION FOR LYNPARZA.
A phase 3 trial evaluating LYNPARZA + bevacizumab vs an active comparator (bevacizumab + placebo) in advanced ovarian cancer1-5
†Select patients for this indication based on an FDA-approved companion diagnostic for LYNPARZA.1
‡Including BRCA mutation (as determined by Myriad MyChoice® CDx) and other causes of HRD. HRD positive is defined as either a tBRCA mutation and/or an HRD score ≥42 by Myriad MyChoice® CDx.3
FDA approval was based on a prespecified exploratory HRD-positive subgroup.
Clinically significant PFS1,2
3.1 years (37.2 months) mPFS with LYNPARZA + bevacizumab vs
~1.5 years (17.7 months) mPFS with bevacizumab + placebo1,2,5
67%
risk reduction of disease progression or death;
HR=0.33 (95% CI: 0.25–0.45)
§Bevacizumab was administered for a total of up to 15 months, including the period given with chemotherapy and given as maintenance.1
||LYNPARZA was continued for up to 2 years or until progression of the underlying disease or unacceptable toxicity. Patients, who in the opinion of the treating physician could derive further benefit from continuous treatment, could be treated beyond 2 years.1
¶Patients with a complete response should stop treatment at 2 years. Patients with evidence of disease at 2 years can remain on therapy at physician discretion. In PAOLA-1, it was unknown how many HRD-positive patients remained on therapy longer than 2 years; therefore, results should be interpreted with caution.1
Data based upon a prespecified exploratory subgroup analysis, which was not controlled for Type 1 error. HRD status was not a stratification factor in PAOLA-1. This trial was not designed to assess a statistical difference between treatment groups at 2 years.
HRD-positive subgroup (n=387)
Events, n (%): 87/255 (34) with LYNPARZA + bevacizumab and 92/132 (70) with bevacizumab + placebo.
ITT population (n=806)
Statistically significant improvement in PFS was observed for LYNPARZA + bevacizumab compared with bevacizumab + placebo.
HRD-negative subgroup (n=277)
Results from an exploratory analysis in this subgroup (HR=1.00 [95% CI: 0.75–1.34]) indicated that the clinical benefit was primarily attributed to the results seen in the HRD-positive subgroup.
Additional subgroup analyses:
In HRD-positive, non-BRCAm patients, median PFS in the LYNPARZA + bevacizumab arm was 28.1 months, and median PFS in the bevacizumab + placebo arm was 16.6 months. HR=0.43 (95% CI: 0.28–0.66 [prespecified exploratory analysis])
In BRCAm patients, median PFS in the LYNPARZA + bevacizumab arm was 37.2 months, and median PFS in the bevacizumab + placebo arm was 21.7 months. HR=0.31 (95% CI: 0.20–0.47 [stratified subgroup])
There was insufficient evidence to suggest differential efficacy between the 2 groups.
Overall survival data
Secondary endpoint: Prespecified exploratory analysis of OS in the HRD-positive subgroup
~6.3 years (75.2 months) mOS with LYNPARZA + bevacizumab vs
~4.8 years (57.3 months) with bevacizumab + placebo1,4
~1.5 years longer mOS with LYNPARZA + bevacizumab
38%
reduction in risk of death (HR=0.62 [95% CI: 0.45–0.85]) with LYNPARZA
+ bevacizumab vs established maintenance bevacizumab + placebo
§Bevacizumab was administered for a total of up to 15 months, including the period given with chemotherapy and given as maintenance.1
||LYNPARZA was continued for up to 2 years or until progression of the underlying disease or unacceptable toxicity. Patients, who in the opinion of the treating physician could derive further benefit from continuous treatment, could be treated beyond 2 years.1
¶Patients with a complete response should stop treatment at 2 years. Patients with evidence of disease at 2 years can remain on therapy at physician discretion. In PAOLA-1, it was unknown how many HRD-positive patients remained on therapy longer than 2 years; therefore, results should be interpreted with caution.1
Data based upon a prespecified exploratory subgroup analysis, which was not controlled for Type 1 error. HRD status was not a stratification factor in PAOLA-1. The analysis is based on Kaplan–Meier estimates and is descriptive only. This trial was not designed to assess a statistical difference between treatment groups at 5 years.
HRD-positive subgroup (n=387)
Events, n (%): 93/255 (36) with LYNPARZA + bevacizumab and 69/132 (52) with bevacizumab + placebo.
ITT population (n=806)
Statistical significance in OS was not reached for LYNPARZA + bevacizumab compared with bevacizumab + placebo.
HRD-negative subgroup (n=277)
Results from an exploratory analysis in this subgroup (HR=1.18 [95% CI: 0.87–1.60]) indicated that the clinical benefit was primarily attributed to the results seen in the HRD-positive subgroup.
Additional prespecified exploratory OS subgroup analyses:
HRD-positive, non-BRCAm patients: HR=0.71 (95% CI: 0.45–1.13)
BRCAm patients: HR=0.60 (95% CI: 0.39–0.93)
There was insufficient evidence to suggest differential efficacy between the 2 groups.
BRCAm status was determined by central labs; HRD status was determined by Myriad MyChoice® HRD Plus.
LONG-TERM PFS data
Post hoc 5-year follow-up analysis of PFS
3.9 years (46.8 months) mPFS with LYNPARZA + bevacizumab
~1.5 years (17.6 months) mPFS with bevacizumab + placebo
59%
risk reduction of disease progression or death;
HR=0.41 (95% CI: 0.32–0.54)
~1 in 2 patients were living progression-free at 5 years: ~46% with LYNPARZA + bevacizumab and ~19% with bevacizumab + placebo1,2,4
Median PFS follow-up time (post hoc follow-up analysis): Efficacy and safety were assessed with long-term follow-up of 5 years after the last patient was randomized (5.1 years for LYNPARZA + bevacizumab and 5.2 years for bevacizumab + placebo); DCO: March 22, 2022.4
The 5-year follow-up analysis of PFS was conducted at the same time point as the OS analysis.4
§Bevacizumab was administered for a total of up to 15 months, including the period given with chemotherapy and given as maintenance.1
||LYNPARZA was continued for up to 2 years or until progression of the underlying disease or unacceptable toxicity. Patients, who in the opinion of the treating physician could derive further benefit from continuous treatment, could be treated beyond 2 years.1
¶Patients with a complete response should stop treatment at 2 years. Patients with evidence of disease at 2 years can remain on therapy at physician discretion. In PAOLA-1, it was unknown how many HRD-positive patients remained on therapy longer than 2 years; therefore, results should be interpreted with caution.1
Data based upon a post hoc analysis of a prespecified exploratory subgroup, which was not controlled for Type 1 error. This analysis is based on Kaplan–Meier estimates and is descriptive only. HRD status was not a stratification factor in PAOLA-1. This trial was not designed to assess a statistical difference between treatment groups at 5 years.
HRD-positive subgroup (n=387)
Events, n (%): 136/255 (53) events with LYNPARZA + bevacizumab and 104/132 (79) events with bevacizumab + placebo.
PFS by clinical risk
In a post hoc exploratory subgroup analysis of PFS by clinical risk for relapse in HRD-positive patients6
mPFS in lower-risk HRD-positive patients: NR with LYNPARZA + bevacizumab and ~1.8 years with bevacizumab + placebo6
Lower-risk patients:
- FIGO stage III and no residual disease following primary debulking
| LYNPARZA + bevacizumab (n=78) |
Bevacizumab + placebo (n=43) |
|
|---|---|---|
| Median PFS (mo) | NR | 22.1 |
| HR=0.15 (95% CI: 0.07–0.30) | ||
Data based upon a post hoc analysis of an exploratory subgroup, which was not controlled for Type 1 error. This analysis is based on Kaplan–Meier estimates and is descriptive only. This trial was not designed to assess a statistical difference between these treatment groups at 2 years. There is no clinical consensus on the definitions of lower vs higher risk.
There was insufficient evidence to suggest differential efficacy between the 2 groups.2,5
Lower Risk
In HRD-positive, non-BRCAm patients, median PFS in the LYNPARZA + bevacizumab arm was 39.3 months* and 23.4 months in the bevacizumab + placebo arm. HR=0.19 (95% CI: 0.06–0.55 [exploratory analysis])6
In BRCAm patients, median PFS in the LYNPARZA + bevacizumab arm was NR and 22.2 months in the bevacizumab + placebo arm. HR=0.11 (95% CI: 0.03–0.31 [exploratory analysis])6
mPFS in higher-risk HRD-positive patients: 3 years with LYNPARZA + bevacizumab and ~1.3 years with bevacizumab + placebo6
Higher-risk patients:
- FIGO stage IV
- FIGO stage III and residual disease following primary debulking
- FIGO stage III patients with interval surgery
| LYNPARZA + bevacizumab (n=177) |
Bevacizumab + placebo (n=89) |
|
|---|---|---|
| Median PFS (mo) | 36.0* | 16.0 |
| HR=0.39 (95% CI: 0.28–0.54) | ||
Higher Risk
In HRD-positive, non-BRCAm, median PFS in the LYNPARZA + bevacizumab arm was 20.3 months and 15.4 months in the bevacizumab + placebo arm. HR=0.51 (95% CI: 0.31–0.83 [exploratory analysis])6
In BRCAm patients, median PFS in the LYNPARZA + bevacizumab arm was 36.0 months* and 19.4 months in the bevacizumab + placebo arm. HR=0.37 (95% CI: 0.23–0.59 [exploratory analysis])6
Data based upon a post hoc analysis of an exploratory subgroup, which was not controlled for Type 1 error. This analysis is based on Kaplan–Meier estimates and is descriptive only. This trial was not designed to assess a statistical difference between these treatment groups at 2 years. There is no clinical consensus on the definitions of lower vs higher risk.
There was insufficient evidence to suggest differential efficacy between the 2 groups.2,5
There is no official clinical consensus on what is considered lower vs higher risk. Data are based on post hoc exploratory subgroup analyses in 2 clinical subgroups (lower risk and higher risk), including biomarker status. Neither HRD status nor risk factor was a stratification factor in PAOLA-1.2,5
*Unstable median due to lack of events.5
Overall survival by clinical risk
Post hoc exploratory subgroup analysis of OS by clinical risk in HRD-positive patients7
Lower-risk patients: Overall survival with LYNPARZA + bevacizumab and bevacizumab + placebo
| LYNPARZA + bevacizumab (n=78) |
bevacizumab + placebo (n=43) |
|
|---|---|---|
| Events, n (%) | 11 (14) | 16 (37) |
| Median OS (mo) | NR | NR |
| 5-year OS rate, % | 88 | 61 |
| HR=0.31 (95% CI: 0.14–0.66) | ||
| LYNPARZA + bevacizumab (n=78) |
bevacizumab + placebo (n=43) |
|
|---|---|---|
| Events, n (%) | 11 (14) | 16 (37) |
| Median OS (mo) | NR | NR |
| 5-year OS rate, % | 88 | 61 |
| HR=0.31 (95% CI: 0.14–0.66) | ||
Patients receiving a PARP inhibitor during any subsequent treatment: 14% in the LYNPARZA arm and 40% in the placebo arm.7
Higher-risk patients: Overall survival with LYNPARZA + bevacizumab and bevacizumab + placebo
| LYNPARZA + bevacizumab (n=177) |
Bevacizumab + placebo (n=89) |
|
|---|---|---|
| Events, n (%) | 82 (46) | 23 (60) |
| Median OS (mo) | 67.0* | 54.0 |
| 5-year OS rate, % | 55 | 42 |
| HR=0.70 (95% CI: 0.50–1.00) | ||
| LYNPARZA + bevacizumab (n=177) |
Bevacizumab + placebo (n=89) |
|
|---|---|---|
| Events, n (%) | 82 (46) | 23 (60) |
| Median OS (mo) | 67.0* | 54.0 |
| 5-year OS rate, % | 55 | 42 |
| HR=0.70 (95% CI: 0.50–1.00) | ||
Patients receiving a PARP inhibitor during any subsequent treatment: 19% in the LYNPARZA arm and 56% in the placebo arm.7
This analysis is based on Kaplan–Meier estimates and is descriptive only. This trial was not designed to assess a statistical difference between these treatment groups at 5 years.
There was insufficient evidence to suggest differential overall survival between the 2 groups.2,5
There is no official clinical consensus on what is considered lower vs higher risk. Data are based on post hoc exploratory subgroup analyses in 2 clinical subgroups (lower risk and higher risk), including biomarker status. Neither HRD status nor risk factor was a stratification factor in PAOLA-1, and analysis was not controlled for Type 1 error.2,5
*Unstable median due to lack of events.7
PAOLA-1 TRIAL DESIGN
PAOLA-1 is the first phase 3 trial to investigate a PARP inhibitor combination regimen against an active and established maintenance therapy: bevacizumab1,8-11
PAOLA-1 studied LYNPARZA + bevacizumab vs an active comparator (bevacizumab + placebo) in advanced ovarian cancer1,2,4,5
*Patients continued bevacizumab in the maintenance setting and started treatment with LYNPARZA after a minimum of 3 weeks and up to a maximum of 9 weeks following completion of their last dose of chemotherapy.
†BRCA mutation status was determined by local laboratories.
||Investigator-assessed PFS evaluated according to RECIST, version 1.1.
¶More endpoints than those noted here were studied in PAOLA-1. Not all results from these endpoints are detailed on this site.1
This study did not implement a prespecified crossover study design.
HRD TESTING
Test for HRD at diagnosis to help identify patients who may be eligible for LYNPARZA + bevacizumab1,12
Approximately half of the patients in the PAOLA-1 trial were HRD positive2
- All trial participants were retrospectively evaluated for HRD using the Myriad MyChoice® CDx1*
- HRD positive was defined as BRCAm and/or genomic instability1,3,12
Prevalence of HRD in the PAOLA-1 overall study population was consistent with HRD prevalence in the general ovarian cancer population.2,13
In a prespecified exploratory analysis of HRD-negative and HRD-unknown patients, there was insufficient evidence to suggest differential efficacy between the combination of LYNPARZA + bevacizumab and bevacizumab + placebo.
Tumor test for HRD, which includes genomic instability,* at diagnosis1,12
| Biomarker | Myriad MyChoice® CDx (HRD, which includes genomic instability*‡) |
|---|---|
| gBRCA§ |  |
| sBRCA | |
| LOH | |
| TAI | |
| LST | |
*HRD positive was defined as either a tBRCA mutation and/or an HRD score ≥42 by Myriad MyChoice® CDx; HRD negative was defined as non–tBRCA-mutated and an HRD score <42 by Myriad MyChoice® CDx. 4.2% of the test results were missing, 2.1% failed, and 11.3% were inconclusive, yielding approximately 18% of the total PAOLA-1 population with an unknown HRD status.3,14
†May include markers of genomic instability (eg, LOH, TAI, LST).12
‡Does not distinguish between somatic and germline on reports.12
§If found to have a BRCA mutation, germline testing may inform genetic risk for patients and their families.15
Key eligibility criteria
Patients enrolled in the overall study population1-3,5:
Stage III or IV advanced ovarian cancer
Included patients regardless of surgical outcome
Upfront or interval debulking surgery, including optimally and suboptimally debulked patients
A range of responses to platinum-based chemotherapy + bevacizumab:
(intravenous, intraperitoneal, or neoadjuvant platinum-based chemotherapy was allowed)
(intravenous, intraperitoneal, or neoadjuvant platinum-based chemotherapy was allowed)
No evidence of disease
Complete response
Partial response
Any patient regardless of BRCA mutation status
Enrolled patients were retrospectively tested for HRD status using Myriad MyChoice® CDx
At least 3 cycles of bevacizumab in combination with platinum-based chemotherapy (~2 months)
Only in the case of interval debulking surgery were 2 cycles of bevacizumab in combination with the last 3 cycles of platinum-based chemotherapy permitted
