PAOLA-1 is the first phase 3 trial to investigate a PARP inhibitor combination regimen against an active and established maintenance therapy: bevacizumab1-5

In PAOLA-1

Primary analysis: Adverse Reactions (ARs) occurring in ≥10% of patients treated with LYNPARZA + bevacizumab and ≥5% frequency compared with placebo + bevacizumab1

Common ARs with LYNPARZA were generally consistent with the known safety profile of LYNPARZA monotherapy1

  • LYNPARZA + bevacizumab (n=535)
  • bevacizumab + placebo (n=267)
Adverse reactions* Grades 1–4 (%) Grades 3–4 (%)
Fatigue (including asthenia)†
  • 53
  • 32
  • 5
  • 1.5
Nausea
  • 53
  • 22
  • 2.4
  • 0.7
Vomiting
  • 22
  • 11
  • 1.7
  • 1.9
Anemia‡
  • 41
  • 10
  • 17
  • 0.4
Lymphopenia§
  • 24
  • 9
  • 7
  • 1.1
Leukopenia||
  • 18
  • 10
  • 1.9
  • 1.5
  • *Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0.
  • †Includes asthenia and fatigue.
  • ‡Includes anemia, anemia macrocytic, erythropenia, hematocrit decreased, hemoglobin decreased, normochromic anemia, normochromic normocytic anemia, normocytic anemia, and red blood cell count decreased.
  • §Includes B-lymphocyte count decreased, lymphocyte count decreased, lymphopenia, and T-lymphocyte count decreased.
  • ||Includes leukopenia and white blood cell count decreased.

Fatal adverse reactions occurred in 1 patient due to concurrent pneumonia and aplastic anemia. Serious adverse reactions occurred in 31% of patients who received LYNPARZA + bevacizumab. Serious adverse reactions in >5% of patients included hypertension (19%) and anemia (17%).

In addition, venous thromboembolism occurred more commonly in patients receiving LYNPARZA + bevacizumab (5%) than in those receiving placebo + bevacizumab (1.9%)

In PAOLA-1

Primary analysis: Lab abnormalities reported in ≥25% of women on LYNPARZA + bevacizumab vs bevacizumab + placebo1*

  • LYNPARZA + bevacizumab (n=535)†
  • bevacizumab + placebo (n=267)†
Laboratory parameter‡ Grades 1–4 (%) Grades 3–4 (%)
Decrease in hemoglobin
  • 79
     
  • 55
     
  •  
    13
  •  
    0.4
Decrease in lymphocytes
  • 63
     
  • 42
     
  •  
    10
  •  
    3
Increase in serum creatinine
  • 61
     
  • 36
     
  •  
    0.4
  •  
    0.4
Decrease in leukocytes
  • 59
     
  • 45
     
  •  
    3.4
  •  
    2.2
Decrease in absolute neutrophil count
  • 35
     
  • 30
     
  •  
    7
  •  
    3.7
Decrease in platelets
  • 35
     
  • 28
     
  •  
    2.4
  •  
    0.4
  • *Reported within 30 days of the last dose.
  • †This number represents the safety population. The derived values in the table are based on the total number of evaluable patients for each laboratory parameter.
  • ‡Patients were allowed to enter clinical studies with laboratory values of CTCAE Grade 1.
In patients receiving LYNPARZA + bevacizumab, dose interruptions of LYNPARZA due to an adverse reaction of any grade occurred in 54% of patients, dose reductions of LYNPARZA due to an adverse reaction occurred in 41% of patients, and discontinuation of LYNPARZA due to an adverse reaction occurred in 20% of patients.1

ARs and laboratory abnormalities from the primary analysis in PAOLA-1 were mostly Grades 1 and 21

At 5-year follow-up analysis6:

  • No new safety signals were identified
  • The incidence of MDS/AML/AA was 1.7% (9/535) in the LYNPARZA + bevacizumab group and 2.2% (6/267) in the bevacizumab + placebo group
    • In the HRD-positive subgroup, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA + bevacizumab and 2.3% (3/131) in patients who received bevacizumab + placebo1
  • 22 (4.1%) new primary malignancy events occurred in the LYNPARZA + bevacizumab group and 8 (3.0%) events occurred in the bevacizumab + placebo group;
  • 7 (1.3%) pneumonitis events occurred in the LYNPARZA + bevacizumab group and 2 (0.7%) events occurred in the bevacizumab + placebo group

At 5-year follow-up analysis6:

  • No new safety signals were identified
  • The incidence of MDS/AML/AA was 1.7% (9/535) in the LYNPARZA + bevacizumab group and 2.2% (6/267) in the bevacizumab + placebo group
    • In the HRD-positive subgroup, the incidence of MDS/AML was 1.6% (4/255) in patients who received LYNPARZA + bevacizumab and 2.3% (3/131) in patients who received bevacizumab + placebo1
  • 22 (4.1%) new primary malignancy events occurred in the LYNPARZA + bevacizumab group and 8 (3.0%) events occurred in the bevacizumab + placebo group;
  • 7 (1.3%) pneumonitis events occurred in the LYNPARZA + bevacizumab group and 2 (0.7%) events occurred in the bevacizumab + placebo group

Summary of adverse reactions of special interest for bevacizumab in the PAOLA-1 study7

  • LYNPARZA
    +
    bevacizumab
    (n=535)
  • Placebo
    +
    bevacizumab
    (n=269)
Adverse event, n (%) All grades Grade ≥3 All grades Grade ≥3
Hypertension 245 (46) 100 (19) 160 (60) 81 (30)
Proteinuria 31 (6) 5 (1) 40 (15) 40 (15)
Tooth abscess 15 (3) 1 ( <1) 4 (1) 0
Pulmonary embolism 7 (1) 7 (1) 1 ( <1) 1 ( <1)
Venous thrombosis 5 (1) 1 ( <1) 2 (1) 0
Thrombosis 5 (1) 0 1 ( <1) 1 ( <1)
Embolism 4 (1) 3 (1) 0 0
Intestinal perforation 1 ( <1) 1 ( <1) 2 (1) 2 (1)
Wound dehiscence 1 ( <1) 1 ( <1) 1 ( <1) 0
Wound evisceration 1 ( <1) 1 ( <1) 1 ( <1) 0
Hemorrhagic disorder 1 ( <1) 1 ( <1) 0 0
Chronic cardiac failure 1 ( <1) 1 ( <1) 0 0
Abdominal abscess 1 ( <1) 1 ( <1) 0 0
Abdominal wall abscess 1 ( <1) 1 ( <1) 0 0
Anal fistula 1 ( <1) 1 ( <1) 0 0
Intestinal hemorrhage 1 ( <1) 1 ( <1) 0 0
Rectal abscess 1 ( <1) 1 ( <1) 0 0
Urogenital fistula 1 ( <1) 1 ( <1) 0 0
Perirectal abscess 1 ( <1) 1 ( <1) 0 0
Pelvic abscess 1 ( <1) 1 ( <1) 0 0
Oral abscess 1 ( <1) 0 1 ( <1) 0
Subcutaneous abscess 1 ( <1) 0 0 0
Gingival abscess 1 ( <1) 0 0 0
Fistula 1 ( <1) 0 0 0
MI 0 0 4 ( <1) 4 (1)
Gastric hemorrhage 0 0 3 (1) 1 ( <1)
Wound complication 0 0 2 (1) 1 ( <1)
Acute MI 0 0 1 ( <1) 1 ( <1)
Cerebral hemorrhage 0 0 1 ( <1) 1 ( <1)
Posterior reversible encephalopathy syndrome 0 0 1 ( <1) 0
Abscess 0 0 1 ( <1) 0

Certain adverse reactions were also present with LYNPARZA monotherapy.

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IMPORTANT SAFETY INFORMATION