Olaparib as maintenance therapy for patients with gBRCA...
Transcript of 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
Screening patients with pancreatic cancer for gBRCA mutations
Patient eligibility for the POLO study POLO: global study of a PARP inhibitor as maintenance therapy
CR
PR SD
PD
Quick Results are available to the oncologist within 14 days
Please click on the tabs below to view additional information on specific topics
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
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
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
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.
Please click on the tabs below to view additional information on specific topics
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
Screening patients with pancreatic cancer for gBRCA mutations
Patient eligibility for the POLO study POLO: global study of a PARP inhibitor as maintenance therapy
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
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
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
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.