Pancreatic cancer: POLO trial

Abbreviations

No EU-CTR

  • POLO references
    2019-07-25
    Talia Golan
    Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer
Investigated (inv)
Comparator (comp)

OLAP

PLB

92

62

Phase:

3

Randomisation:

Double blind

Primary tumour:

Pancreatic

Subtype (biomarker):

BRCA1/2 MT

Stage:

meta

Line of therapy:

L1

Primary
OLAP
PLB
HR
p
PFS
7.4 mo
3.8 mo
0.53 (0.35-0.82)
0.004
Secondaries
OLAP
PLB
HR
p
OS (46% data)
18.9 mo
18.1 mo
0.91 (0.56-1.46)
0.68
(all grades, %)
OLAP
PLB
p
Any AE grade ≥3
40%
23%
NA
Fatigue or asthenia
60%
35%
NA
Nausea
45%
23%
NA
Anemia
27%
17%
NA
Abdominal pain
29%
25%
NA
Diarrhea
29%
15%
NA
Decreased appetite
25%
7%
NA
Constipation
23%
10%
NA
Vomiting
20%
15%
NA
Back pain
19%
17%
NA
Arthralgia
15%
10%
NA
Interruption of intervention owing to adverse event
35%
5%
NA
Dose reduction owing to adverse event
16%
3%
NA
Discontinuation of intervention owing to adverse event
5%
2%
NA
  • Inclusion
  • Exclusion

- Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment - Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study. - Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious - Patients are on treatment with a first line platinum-based (cisplatin, carboplatin or oxaliplatin) regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator's opinion. - Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.

- gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favour polymorphism" or "benign polymorphism" etc.) - Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation. - Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle 1, Day 1 is not permitted. - Exposure to an investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation - Any previous treatment with a PARP inhibitor, including Olaparib

Characteristics
OLAP
PLB
Agedc-comma sex
Median age (range) yr
57 (37-84)
57 (36-75)
≥65 yr - no(%)
28 (30)
13 (21)
Male - no(%)
53 (58)
31 (50)
ECOG performance status - no(%)
0
65 (71)
38 (61)
1
25 (27)
23 (37)
Missing data
2 (2)
1 (2)
Germline BRCA mutation - no(%)
BRCA1
29 (32)
16 (26)
BRCA2
62 (67)
46 (74)
Both BRCA1 and BRCA2
1 (1)
0
Time from diagnosis to randomizationdc-comma mo
Median
6.9
7.0
Range
3.6–38.4
4.1–30.2
First-line platinum-based chemotherapy - no(%)
FOLFIRINOX variants
79 (86)
50 (81)
Gemcitabine–cisplatin
2 (2)
3 (5)
Other platinum-based treatments
10 (11)
8 (13)
Missing data
1 (1)
1 (2)
Duration of first-line chemotherapy before randomization
Mediandc-comma mo
5.0
5.1
Rangedc-comma mo
2.5–35.2
3.4–20.4
16 wk–6 mo - no(%)
61 (66)
40 (65)
>6 mo - no(%)
30 (33)
21 (34)
Best response with first-line chemotherapy - no(%)
Complete or partial response
46 (50)
30 (48)
Stable disease
45 (49)
31 (50)
Missing data
1 (1)
1 (2)
Ad-hoc:
no.pts inv.
no.pts comp.
OLAP
PLB
HR
p
  • PFS
analisys of PFS
OLAP
PLB
HR (95% CI)
Previous chemotherapy
FOLFIRINOX variants
0.54 (0.35–0.84)
Other
0.76 (0.27–2.32)
Type of previous chemotherapy
Doublet chemotherapy
0.59 (0.24–1.50)
Triplet chemotherapy
0.51 (0.32–0.82)
Duration of first-line treatment before randomization
16 wk-6 mo
0.69 (0.43–1.12)
>6 mo
0.35 (0.17–0.72)
Best response with first-line treatment
Partial or complete response
0.62 (0.35–1.12)
Stable disease
0.50 (0.29–0.87)
Disease at baseline
Measurable
0.57 (0.37–0.88)
Not measurable or no evidence of disease
0.45 (0.14–1.57)
Germline BRCA mutation type
BRCA1
0.40 (0.20–0.85
BRCA2
0.63 (0.39–1.02)
Age at randomization
<65 yr
0.45 (0.28–0.72)
≥65 yr
1.02 (0.45–2.60)
Sex
Male
0.46 (0.27–0.80)
Female
0.66 (0.37–1.19)
Other
White race
0.59 (0.39–0.90)
Absence of biliary stent
0.54 (0.36–0.82)
analisys of
OLAP
PLB
HR (95% CI)