POLO: trial | Bending the Curve: Trial by Trial

POLO

Maintenance olaparib versus placebo in germline BRCA-mutated metastatic pancreatic cancer (POLO)

Population

Germline BRCA1/2-mutated metastatic pancreatic cancer without progression on first-line platinum-based chemotherapy

Design

Randomised (3:2), double-blind, placebo-controlled phase 3 trial of maintenance olaparib 300 mg tablets twice daily versus placebo in patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy (at least 16 weeks, per the final analysis report). Primary endpoint progression-free survival by blinded independent central review.

Primary endpoint

PFS

Arms

Olaparib (experimental, n = 92): Olaparib 300 mg orally twice daily (maintenance)
Placebo (control, n = 62): Placebo (maintenance)

People

Golan T

PFSHR 0.53 (95% CI 0.35–0.82)Δ median PFS+3.6 monthsOSHR 0.91 (95% CI 0.56–1.46)Δ median OS+0.8 monthsOSHR 0.83 (95% CI 0.56–1.22)Δ median OS−0.2 months

Show the numbers

Results reported for POLO
Endpoint	Analysis	Olaparib	Placebo	Effect
PFSITT (all randomised patients, 154)Blinded independent central review	primaryGolan 2019	median 7.4 months	median 3.8 months	HR 0.53 (95% CI 0.35–0.82)P=0.004
OSITT (all randomised patients, 154)	interimGolan 2019	median 18.9 months	median 18.1 months	HR 0.91 (95% CI 0.56–1.46)P=0.68Interim analysis at a data maturity of 46%.
OSITT (all randomised patients, 154)	finalKindler 2022	median 19 months; 33.9% at 3 y	median 19.2 months; 17.8% at 3 y	HR 0.83 (95% CI 0.56–1.22)P=.3487No statistically significant overall survival benefit. Survival curves separated at about 24 months; the 3-year figures are estimates of survival after randomisation.

Results reported for POLO
Endpoint	Analysis	Olaparib	Placebo	Effect
PFSITT (all randomised patients, 154)Blinded independent central review	primaryGolan 2019	median 7.4 months	median 3.8 months	HR 0.53 (95% CI 0.35–0.82)P=0.004
OSITT (all randomised patients, 154)	interimGolan 2019	median 18.9 months	median 18.1 months	HR 0.91 (95% CI 0.56–1.46)P=0.68Interim analysis at a data maturity of 46%.
OSITT (all randomised patients, 154)	finalKindler 2022	median 19 months; 33.9% at 3 y	median 19.2 months; 17.8% at 3 y	HR 0.83 (95% CI 0.56–1.22)P=.3487No statistically significant overall survival benefit. Survival curves separated at about 24 months; the 3-year figures are estimates of survival after randomisation.

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
PFS	0.53	0.35–0.82
OS	0.91	0.56–1.46
OS	0.83	0.56–1.22

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Olaparib (experimental)
Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Olaparib	Placebo
0	100.0%	100.0%
5	62.6%	40.2%
9	43.0%	19.4%
14	26.9%	7.8%
19	16.9%	3.1%

Illustrative — modelled from reported values, not trial data. OS, interim.

Show curves

Olaparib (experimental)
Placebo (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Olaparib	Placebo
0	100.0%	100.0%
12	64.4%	63.2%
24	41.5%	39.9%
35	27.7%	26.2%
47	17.8%	16.5%

Appears in

2019 POLO: maintenance olaparib for germline BRCA-mutated disease

Sources

Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019;381(4):317-327.
PubMed DOI
Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, et al. Overall Survival Results From the POLO Trial: A Phase III Study of Active Maintenance Olaparib Versus Placebo for Germline BRCA-Mutated Metastatic Pancreatic Cancer. J Clin Oncol. 2022;40(34):3929-3939.
PubMed DOI