Pancreatic cancer, BRCA-mutated

Back to Top
Are you looking for a regimen, but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it! 
Note: this page has regimens which are specific to pancreatic cancer that is BRCA-mutated. Please see the main pancreatic cancer page for other chemotherapy regimens.
Last updated on 2024-07-23:3 regimens on this page
3 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Pancreatic Adenocarcinoma.
=Advanced or metastatic disease, first-line=
==Cisplatin & Gemcitabine (GC)==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
O'Reilly et al. 2020 (MSKCC 12-045)	2014-2018 	Randomized Phase 2 (C)	GC & Veliparib	Did not meet primary endpoint of RR
Selected inclusion criteria: germline BRCA1/2 or PALB2 mutation and previously untreated stage III-IV pancreatic adenocarcinoma. The addition of veliparib did not improve RR.
====Biomarker eligibility criteria====
*Germline BRCA1/2 or PALB2+ mutation
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV once per day on days 3 & 10
*Gemcitabine (Gemzar) 600 mg/m2 IV over 30 minutes once per day on days 3 & 10
21-day cycles
===References===
#MSKCC 12-045: O'Reilly EM, Lee JW, Zalupski M, Capanu M, Park J, Golan T, Tahover E, Lowery MA, Chou JF, Sahai V, Brenner R, Kindler HL, Yu KH, Zervoudakis A, Vemuri S, Stadler ZK, Do RKG, Dhani N, Chen AP, Kelsen D. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin With or Without Veliparib in Patients With Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J Clin Oncol. 2020 May 01;38:1378-1388. Epub 2020 Jan 24. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01585805
=Maintenance after first-line therapy=
==Olaparib monotherapy==
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Golan et al. 2019 (POLO)	2015-2019 	Phase 3 (E-RT-esc)	Placebo 	Longer PFS (primary endpoint)Median PFS: 7.4 vs 3.8 mo(HR 0.53, 95% CI 0.35-0.82)
Selected inclusion criteria: germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy.
====Biomarker eligibility criteria====
*Germline BRCA1 or BRCA2 mutation
====Preceding treatment====
*First-line platinum-based chemotherapy for at least 16 weeks
====Targeted therapy====
*Olaparib (Lynparza) 300 mg PO twice per day
Continued indefinitely
===References===
#POLO: Golan T, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Schlienger K, Locker GY, Kindler HL. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019 Jul 25;381(4):317-327. Epub 2019 Jun 2. link to original article dosing details in abstract have been reviewed by our editors link to PMC article EuroPMC NCT02184195
##HRQoL analysis: Hammel P, Kindler HL, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, McGuinness D, Cui KY, Joo S, Yoo HK, Patel N, Golan T; POLO Investigators. Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib. Ann Oncol. 2019 Dec 1;30(12):1959-1968. link to original article link to PMC article EuroPMC
##Update: Kindler HL, Hammel P, Reni M, Van Cutsem E, Macarulla T, Hall MJ, Park JO, Hochhauser D, Arnold D, Oh DY, Reinacher-Schick A, Tortora G, Algül H, O'Reilly EM, Bordia S, McGuinness D, Cui K, Locker GY, Golan T. 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 Dec 1;40(34):3929-3939. Epub 2022 Jul 14. link to original article link to PMC article EuroPMC
##TWiST analysis: Kindler HL, Yoo HK, Hettle R, Cui KY, Joo S, Locker GY, Golan T. Patient-centered outcomes in the POLO study of active maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. Cancer. 2023 May 1;129(9):1411-1418. Epub 2023 Feb 22. link to original article EuroPMC
=Metastatic disease, refractory=
==Olaparib monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence
Kaufman et al. 2014 (Study 42)	2010-02-21 to 2012-07-31	Phase 2
====Biomarker eligibility criteria====
*Germline BRCA1/2 mutations
====Prior treatment criteria====
*Gemcitabine, with progression
====Targeted therapy====
*Olaparib (Lynparza) 400 mg PO twice per day
Continued indefinitely
===References===
#Study 42: Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT01078662
=Additional resources=
*OncoMX -- BRCA1
*OncoMX -- BRCA2
Category:Pancreatic cancer regimens
Category:Biomarker-specific pages
Category:Gastrointestinal cancers