Difference between revisions of "Pancreatic cancer, BRCA-mutated"
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===References=== | ===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. [https:// | + | #'''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. [https://doi.org/10.1056/NEJMoa1903387 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963 PubMed] NCT02184195 |
==Placebo== | ==Placebo== | ||
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===References=== | ===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. [https:// | + | #'''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. [https://doi.org/10.1056/NEJMoa1903387 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810605/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31157963 PubMed] NCT02184195 |
=Metastatic disease, refractory= | =Metastatic disease, refractory= | ||
Revision as of 14:03, 15 September 2022
3 regimens on this page
3 variants on this page
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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
- Cisplatin (Platinol) 25 mg/m2 IV once per day on days 3 & 10
- Gemcitabine (Gemzar) 600 mg/m2 IV 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. 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
- 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 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
- Platinum-based chemotherapy for at least 16 weeks
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 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.
Preceding treatment
- 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 contains dosing details in manuscript link to PMC article PubMed NCT01078662