olaparib as maintenance therapy for patients with gbrca...

Olaparib as maintenance therapy for patients with gBRCA-mutated metastatic pancreatic cancer: phase III POLO study

The PARP inhibitor olaparib showed promising efficacy in patients with gBRCA-mutated metastatic pancreatic cancer 4

Please click on the tabs below to view additional information on specific topics

POLO is a phase III, placebo-controlled study of olaparib as first-line maintenance therapy for patients with gBRCA-mutated metastatic pancreatic cancer11,12

Current ESMO Guidelines

suggest that patients with gBRCA-mutated metastatic pancreatic cancer may also be sensitive to PARP inhibitors2

Maintenance therapy, following first-line treatment

• Shown benefit in ovarian cancer9

• Promising efficacy in a phase II study of a targeted agent in pancreatic cancer10

• Offers disease control benefits5,6

• Recommended for colorectal7

and non-small-cell lung cancer 8

It is important to identify all patients with newly-diagnosed metastatic pancreatic cancer who have gBRCA-mutated pancreatic cancer, as they may benefit from platinum chemotherapy and be eligible for inclusion in the POLO study

Should not be limited by family history, ethnicity or other characteristics

Ideally done at the same time as histological confirmation of the disease

...BUT can be done anytime from diagnosis up to a pause in first-line platinum-based chemotherapy

Patients with gBRCA-mutated metastatic pancreatic cancer form a distinct molecular subgroup3

The incidence of gBRCA1/2-mutated pancreatic cancer varies

4–5%

7% New York study in non-predisposed patients15

Literature reports13,14 First 1,033 patients screened in POLO16

Screening for gBRCA

6.6%

including the 14 additional patients

with known gBRCA1/2 mutations

68 patients with newly identified

gBRCA1/2 mutations

The prognosis for pancreatic cancer has not markedly improved over the past 20 years1,2

Patients with gBRCA-mutated pancreatic cancer are sensitive to platinum -based chemotherapy2,3

Screening patients with pancreatic cancer for gBRCA mutations

Patient eligibility for the POLO study POLO: global study of a PARP inhibitor as maintenance therapy

If you have any queries or would like any additional information, please contact Gershon Locker MD, Senior Director of Clinical Research, AstraZeneca, [email protected]

Date of preparation: July 2016

References 1. Carnevale J, Ashworth A. J Clin Oncol 2015;33:3080–1. 2. Ducreux M, et al. Ann Oncol 2015;26(Suppl. 5):v56–68. 3. Golan T, et al. Br J Cancer 2014;111:1132–8. 4. Kaufman B, et al. J Clin Oncol 2013;31(Suppl.):Abstr. 11024. 5. Blais N, Kassouf E. Front Oncol 2014;4:213. 6. Marshall JL. Oncology (Williston Park). 2014;28:322, 324. 7. Van Cutsem E, et al. Ann Oncol 2014;25(Suppl. 3):iii1–9. 8. Reck M, et al. Ann Oncol 2014;25(Suppl. 3):iii27–39. 9. Vaccaro V, et al. World J Gastroenterol 2015;21:4788–801. 10. Reni M, et al. Eur J Cancer 2013;49:3609–15. 11. Kindler HL, et al. J Clin Oncol 2015;33(Suppl.):Abstr TPS4149. 12. ClinicalTrials.gov. NCT02184195. https://clinicaltrials.gov/ct2/show/NCT02184195. Accessed March 2016. 13. Waddell N, et al. Nature 2015;518:495–501. 14. Holter S, et al. J Clin Oncol 2015:33:3124–9.15. Salo-Mullen EE, et al. Cancer 2015;121:4382–8. 16. AstraZeneca, data on file. 2016.

Abbreviations BID – twice daily; CR – complete response; DCR – disease control rate; ESMO – European Society for Medical Oncology; gBRCA – germline BRCA; ORR – overall response rate; OS – overall survival; PARP – poly ADP ribose polymerase; PD – progressive disease; PFS – progression-free survival; POLO – Pancreas OLaparib Ongoing Trial; RECIST – Response Evaluation Criteria In Solid Tumors.

Following this guidance ensures that all eligible patients start receiving study treatment at the appropriate time

All patients need to be tested for gBRCA mutations. gBRCA mutation status can be determined by prior local laboratory testing or by central testing using the Myriad Integrated BRACAnalysis test

To be eligible for POLO, patients with gBRCA-mutated metastatic pancreatic cancer must have no evidence of disease progression, by investigator assessment

gBRCA testing for the POLO study

after the last chemotherapy infusion

Eligible for POLO Not eligible for POLO

Response to first-line platinum-based chemotherapy

Study treatment (olaparib or placebo) should be initiated

no less than 4 weeks

and no more than 8 weeks

Week

1Week

5Week

3Week

7Week

2Week

6Week

4Week

8Week

9

Prolonged platinum chemotherapy may preclude enrolment Patients are more likely to suffer prolonged side effects Study excluding laboratory abnormalities are more likely to emerge

Disease progression is more likely to occur

To be eligible for POLO, patients with gBRCA-mutated metastatic pancreatic adenocarcinoma are required to have received ≥16 weeks of platinum-based chemotherapy as first-line treatment at a time when the physician and patient believe a pause in chemotherapy is appropriate

≥ 16 Weeks

Reliable Myriad has over 20 years of testing experience in the USA, with over 1 million genetic tests performed

Reimbursed AstraZeneca is funding Myriad’s Integrated BRACAnalysis test

Simple A blood test



CR

PR SD

PD

Quick Results are available to the oncologist within 14 days




















For a full description of the study design, including details of the inclusion and exclusion criteria, please see the POLO study protocol

Study endpoints

Primary: PFS1 (by central review)

Selected secondary: OS, PFS2 by investigator assessment, ORR, DCR, safety, quality of life

POLO (NCT02184195) is a double-blind, randomised study11,12

Determine patients’

gBRCA mutation status and other eligibility criteria

Randomise patients with gBRCA1/2 mutations

Disease progression by

RECIST

Resume chemo

Disease progression by

investigator assessment

Treat according to local standard

Olaparib (300 mg BID)

Placebo

3:2N=145

PFS1

PFS2Following a pause in first-line platinum chemotherapy

POLO is the only phase III study to screen patients with metastatic pancreatic cancer for gBRCA mutations

Mid

2017

Screening will continue until First data available

1st half

2018




















olaparib as maintenance therapy for patients with gbrca...

Documents