Efficacy of olaparib maintenance therapy in BRCA1 germline mutations in familial pancreatic cancer patient
https://doi.org/10.21518/ms2023-231
Abstract
Pancreatic cancer (PaCa) is one of the most aggressive and unfavourable current oncological diseases. The vast majority of patients have unresectable or metastatic disease at diagnosis. Despite considerable achievements in the drug therapy of most malignant tumours, the immediate and long-term results of the treatment of PaCa still remain extremely unsatisfactory, as overall survival at 5 years does not exceed 10%. The high molecular genetic heterogeneity, which is characteristic of pancreatic adenocarcinomas, the low frequency of driver changes, the diagnostic difficulties, and the rapid progressive deterioration of the general health condition of most patients are just a few of the reasons for the lack of highly specific treatment. Understanding that about 10–15% of pancreatic tumours are a manifestation of genetically determined syndromes has changed the pharmaceutical treatment options for this cohort of patients. BRCA1/2 mutation carrier status is one of these reasons, while the relative risk of PaCa is 2.36 in BRCA1 mutation and 3.34 in BRCA2, respectively. The PARP inhibitor therapy experience and proven efficacy allowed to successfully use this group of drugs in the treatment of BRCA-mutated ovarian and breast cancers. The double-blind, placebo-controlled phase III POLO trial showed the benefit of olaparib as maintenance therapy in BRCA-mutated PaCa. This article presents a clinical case report of the use of olaparib in a patient with familial BRCA1-mutated metastatic PaCa.
About the Authors
A. L. KornietskayaRussian Federation
Anna L. Kornietskaya, Cand. Sci. (Med.), Leading Researcher, Department of Drug Treatment of Tumors
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
L. V. Bolotina
Russian Federation
Larisa V. Bolotina, Dr. Sci. (Med.), Head of Chemotherapy Department
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
S. F. Evdokimova
Russian Federation
Sevindzh F. Evdokimova, Postgraduate Student
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
N. S. Prizova
Russian Federation
Natalia S. Prizova, Cand. Sci. (Med.), Oncologist of Chemotherapy Department
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
T. V. Ustinova
Russian Federation
Tatyana V. Ustinova, Cand. Sci. (Med.), Department of Chemotherapy
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
T. I. Deshkina
Russian Federation
Tatiana I. Deshkina, Cand. Sci. (Med.), Senior Researcher, Department of Chemotherapy
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
A. A. Fedenko
Russian Federation
Alexander A. Fedenko, Dr. Sci. (Med.), Head of Chemotherapy Department
3, 2nd Botkinskiy Proezd, Moscow, 125834, Russia
References
1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209–249. https://doi.org/10.3322/caac.21660.
2. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. https://doi.org/10.3322/caac.21654.
3. Sohal D.P., Mangu P.B., Khorana A.A., Shah M.A, Philip P.A., O’Reilly E.M. et al. Metastatic Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016;34(23):2784–2796. https://doi.org/10.1200/JCO.2016.67.1412.
4. Conroy T., Desseigne F., Ychou M., Bouché O., Guimbaud R., Bécouarn Y. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825. https://doi.org/10.1056/NEJMoa1011923.
5. Von Hoff D.D., Ervin T., Arena F.P., Chiorean E.G., Infante J., Moore M. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–1703. https://doi.org/10.1056/NEJMoa1304369.
6. Burris H.A. 3rd, Moore M.J., Andersen J., Green M.R., Rothenberg M.L., Modiano M.R. et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403–2413. https://doi.org/10.1200/JCO.1997.15.6.2403.
7. Swayden M., Iovanna J., Soubeyran P. Pancreatic cancer chemo-resistance is driven by tumor phenotype rather than tumor genotype. Heliyon. 2018;4(12):e01055. https://doi.org/10.1016/j.heliyon.2018.e01055.
8. Klein A.P. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012;51(1):14–24. https://doi.org/10.1002/mc.20855.
9. Klein A.P., Brune K.A., Petersen G.M., Goggins M., Tersmette A.C., Offerhaus G.J. et al. Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004;64(7):2634–2638. https://doi.org/10.1158/0008-5472.can-03-3823.
10. Hiripi E., Lorenzo Bermejo J., Li X., Sundquist J., Hemminki K. Familial association of pancreatic cancer with other malignancies in Swedish families. Br J Cancer. 2009;101(10):1792–1797. https://doi.org/10.1038/sj.bjc.6605363.
11. Schneider R., Slater E.P., Sina M., Habbe N., Fendrich V., Matthäi E. et al. German national case collection for familial pancreatic cancer (FaPaCa): ten years experience. Fam Cancer. 2011;10(2):323–330. https://doi.org/10.1007/s10689-010-9414-x.
12. Goggins M., Overbeek K.A., Brand R., Syngal S., Del Chiaro M., Bartsch D.K. et al. Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut. 2020;69(1):7–17. https://doi.org/10.1136/gutjnl-2019-319352.
13. Gardiner A., Kidd J., Elias M.C., Young K., Mabey B., Taherian N. et al. Pancreatic Ductal Carcinoma Risk Associated With Hereditary Cancer-Risk Genes. J Natl Cancer Inst. 2022;114(7):996–1002. https://doi.org/10.1093/jnci/djac069.
14. Vietri M.T., D’Elia G., Caliendo G., Albanese L., Signoriello G., Napoli C., Molinari A.M. Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation. Genes (Basel). 2022;13(2):321. https://doi.org/10.3390/genes13020321.
15. Murphy K.M., Brune K.A., Griffin C., Sollenberger J.E., Petersen G.M., Bansal R. et al. Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%. Cancer Res. 2002;62(13):3789–3793. https://pubmed.ncbi.nlm.nih.gov/12097290/
16. George A., Kaye S., Banerjee S. Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer. Nat Rev Clin Oncol. 2017;14(5):284–296. https://doi.org/10.1038/nrclinonc.2016.191.
17. Li S., Silvestri V., Leslie G., Rebbeck T.R., Neuhausen S.L., Hopper J.L. et al. Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants. J Clin Oncol. 2022;40(14):1529–1541. https://doi.org/10.1200/JCO.21.02112
18. Farmer H., McCabe N., Lord C.J., Tutt A.N., Johnson D.A., Richardson T.B. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–921. https://doi.org/10.1038/nature03445.
19. Kindler H.L., Hammel P., Reni M., Van Cutsem E., Macarulla T., Hall M.J. et al. 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;40(34):3929–3939. https://doi.org/10.1200/JCO.21.01604.
20. Axilbund J.E., Argani P., Kamiyama M., Palmisano E., Raben M., Borges M. et al. Absence of germline BRCA1 mutations in familial pancreatic cancer patients. Cancer Biol Ther. 2009;8(2):131–135. https://doi.org/10.4161/cbt.8.2.7136.
21. Hahn S.A., Greenhalf B., Ellis I., Sina-Frey M., Rieder H., Korte B. et al. BRCA2 germline mutations in familial pancreatic carcinoma. J Natl Cancer Inst. 2003;95(3):214–221. https://doi.org/10.1093/jnci/95.3.214.
22. Couch F.J., Johnson M.R., Rabe K.G., Brune K., de Andrade M., Goggins M. et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2007;16(2):342–346. https://doi.org/10.1158/1055-9965.EPI-06-0783.
Review
For citations:
Kornietskaya AL, Bolotina LV, Evdokimova SF, Prizova NS, Ustinova TV, Deshkina TI, Fedenko AA. Efficacy of olaparib maintenance therapy in BRCA1 germline mutations in familial pancreatic cancer patient. Meditsinskiy sovet = Medical Council. 2023;(11):172-177. (In Russ.) https://doi.org/10.21518/ms2023-231