Pancreatic cancer, BRCA-mutated

Section editor
	Eric I. Marks, MD Boston University Boston, MA, USA

3 regimens on this page 3 variants on this page

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.

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

1. 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 contains dosing details in manuscript PubMed 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	Superior 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

1. 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 contains dosing details in abstract link to PMC article PubMed NCT02184195
   1. 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 PubMed
   2. 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 PubMed

Placebo

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Golan et al. 2019 (POLO)	2015-2019	Phase 3 (C)	Olaparib	Inferior PFS

Preceding treatment

• First-line platinum-based chemotherapy for at least 16 weeks

References

1. 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 link to PMC article PubMed NCT02184195
   1. 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 PubMed
   2. 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 PubMed

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

1. 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 contains dosing details in manuscript link to PMC article PubMed NCT01078662

Additional resources

• OncoMX -- BRCA1
• OncoMX -- BRCA2