First-line maintenance therapy for patients with gBRCA-mutated metastatic pancreatic cancer whose disease has not progressed on at least 16 weeks of first-line platinum-based chemotherapy1
In the POLO trial, LYNPARZA® nearly doubled median PFS (7.4 months vs 3.8 months with placebo)1
STUDY DESIGN
POLO: A pivotal phase 3 trial1-3
The POLO trial was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial of LYNPARZA® maintenance therapy in patients with gBRCA-mutated* metastatic pancreatic cancer.
Eligibility criteria:
All patients had a deleterious or suspected deleterious germline BRCA mutation as detected by the Myriad BRACAnalysis® or BRACAnalysis CDx® at a central laboratory, a locally performed BRCA test, or both ≥16 weeks of first-line platinum-based chemotherapy with no limit to duration, without evidence of disease progression (complete response, partial response, or stable disease)
Randomisation
N=154 (no stratification)
3:2
Treatment until disease progression or unacceptable toxicity
LYNPARZA® 300 mg BID (n=92)
Placebo BID (n=62)
Trial endpoints1
Primary endpoint
PFS (BICR per modified RECIST, version 1.1)
Select secondary endpoints
OS
ORR (BICR per modified RECIST, version 1.1)
Safety objective
Safety and tolerability
Prior treatment
Previous chemotherapy (LYNPARZA® n=92, placebo n=62): 75% received FOLFIRINOX, 12% received variants of FOLFIRINOX, and 3% received gemcitabine plus cisplatin
A complete or partial response to first-line platinum-based chemotherapy was seen in 49% of patients (LYNPARZA n=92, placebo n=62)
*gBRCAm should be determined by an FDA-approved companion diagnostic for LYNPARZA®.2
In POLO, PFS was defined as the time from randomisation to disease progression or death from any cause. In the LYNPARZA® arm (n=92), there were 55 progression events and 5 death events. Deaths occurred before BICR-documented progression. In the placebo arm (n=62), there were 44 progression events and no deaths.
Estimated proportion of patients who were progression free through 24 months3,†
†Based on Kaplan–Meier estimates.
These analyses are descriptive only; the POLO trial was not powered to assess a statistical difference between treatment groups at these timepoints.
SECONDARY ENDPOINT: OS IN THE POLO TRIAL1
The final analysis of OS did not reach statistical significance (HR=0.83, 95% CI: 0.56–1.22, P=0.3487). Median overall survival was 19.0 months (95% CI: 15.3–26.3) for LYNPARZA® vs 19.2 months (95% CI: 14.3–26.1) for placebo.
Evaluating ORR by BICR2
ORR in patients with measurable disease at baseline (LYNPARZA® [n=78]; placebo [n=52]).
Approximately 84% of patients in the POLO study had measurable disease at baseline after receiving first-line platinum-based chemotherapy.
Almost 1 in 4 patients in the LYNPARZA® group with measurable disease after first-line platinum-based chemotherapy achieved a response (vs almost 1 in 8 in the placebo group), including 2 conversions to complete response.
For patients who responded to LYNPARZA®, the median duration of response was >2 years after platinum-based chemotherapy2,3
Patients evaluated had measurable disease at baseline (as determined by mRECIST v1.1) and developed an objective response to LYNPARZA® (as determined by BICR per mRECIST v1.1).
gBRCAm should be determined by an FDA-approved companion diagnostic for LYNPARZA®.
n=78 patients in the LYNPARZA® group, n=52 patients in the placebo group.
BICR, blinded independent central review; BID, twice daily; BRCAm, BRCA-mutated or BRCA mutations(s); CI, confidence interval; FDA, Food and Drug Administration; gBRCA; germline BRCA; HR, hazard ratio; mo, months; NR, not reached; PFS, progression free survival; ORR, objective response rate; OS, overall survival; RECIST, Response Evaluation Criteria in Solid Tumors.
References: 1. LYNPARZA®. Summary of Product Characteristics. 2. LYNPARZA® (olaparib). Prescribing information. 3. Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381(4):317-327.