Pancreatic cancer, BRCA-mutated

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Eric Marks Headshot.jpg
Eric I. Marks, MD
Boston University
Boston, MA
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.


Advanced or metastatic disease, first-line

Cisplatin & Gemcitabine (GC)

Regimen

Study Years 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

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. link to original article link to PMC article PubMed NCT01585805

Maintenance after first-line therapy

Olaparib monotherapy

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Golan et al. 2019 (POLO) 2015-2019 Phase 3 (E-RT-esc) Placebo Superior PFS
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

Targeted therapy

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

Placebo

Regimen

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

Preceding treatment

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

Metastatic disease, refractory

Olaparib monotherapy

Regimen

Study Evidence
Kaufman et al. 2014 (Study 42) Phase 2

Patients had germline BRCA1/2 mutations.

Prior treatment criteria

  • Gemcitabine, with progression

Targeted therapy

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