Core Homologous Recombination Mutations and Improved Survival in Nonpancreatic GI Cancers.
Journal
American journal of clinical oncology
ISSN: 1537-453X
Titre abrégé: Am J Clin Oncol
Pays: United States
ID NLM: 8207754
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
entrez:
23
3
2022
pubmed:
24
3
2022
medline:
3
5
2022
Statut:
ppublish
Résumé
Homologous recombination mutations (HRM) have led to increased responses to platinum chemotherapy in pancreatic cancer. However, HRMs' role in nonpancreatic gastrointestinal (GI) cancers remains to be determined. Our objective was to evaluate the prognostic and predictive role of core (BRCA1, BRCA2, PALB2) and noncore HRM in nonpancreatic GI cancers receiving platinum therapy. This study performed at Moffitt Cancer Center included metastatic nonpancreatic GI cancer patients treated with platinum therapy. All patients had either a core or noncore HRM, determined by next generation sequencing. Response rates, median progression-free survival (PFS), and median overall survival (OS) were determined and compared between core versus noncore HRM patients. In the study, 69 patients with one or more HRM were included: 63.8% were male, 87.0% were Caucasian, and 47.9% had colorectal cancer. Twenty-one (30.4%) patients had a core HRM and 48 (69.6%) had a noncore HRM. Among evaluable patients (n=64), there was no significant difference in objective response: 20.0% with core HRM versus 22.7% with noncore HRM responded to platinum therapy (P=0.53). Median PFS was 10.4 months versus 7.1 months for core HRM versus noncore HRM, respectively (P=0.039). Median OS was 68.9 months versus 24.3 months (P=0.026) for core HRM versus noncore HRM, respectively. Our study demonstrated response of core and noncore HRM to platinum therapy in metastatic nonpancreatic GI malignancies, suggesting benefit in both groups. Core HRM patients had significantly increased median OS and median PFS compared with those with noncore HRM, suggesting potential prognostic and predictive significance. Larger prospective studies are needed to confirm our findings.
Identifiants
pubmed: 35320814
doi: 10.1097/COC.0000000000000901
pii: 00000421-202204000-00001
doi:
Substances chimiques
Platinum
49DFR088MY
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
137-141Informations de copyright
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Arnold M, Abnet CC, Neale RE, et al. Global burden of 5 major types of gastrointestinal cancer. Gastroenterology. 2020;159:335–349.e15.
Wong W, Raufi AG, Safyan RA, et al. BRCA mutations in pancreas cancer: spectrum, current management, challenges and future prospects. Cancer Manag Res. 2020;12:2731–2742.
Naseem M, Xiu J, Salem ME, et al. Characteristics of colorectal cancer (CRC) patients with BRCA1 and BRCA2 mutations. J Clin Oncol. 2019;37:606–606.
Spizzo G, Puccini A, Xiu J, et al. Frequency of BRCA mutation in biliary tract cancer and its correlation with tumor mutational burden (TMB) and microsatellite instability (MSI). J Clin Oncol. 2019;37:4085–4085.
Wright WD, Shah SS, Heyer WD. Homologous recombination and the repair of DNA double-strand breaks. J Biol Chem. 2018;293:10524–10535.
Li X, Heyer WD. Homologous recombination in DNA repair and DNA damage tolerance. Cell Res. 2008;18:99–113.
Pokataev I, Fedyanin M, Polyanskaya E, et al. Efficacy of platinum-based chemotherapy and prognosis of patients with pancreatic cancer with homologous recombination deficiency: comparative analysis of published clinical studies. ESMO Open. 2020;5:e000578.
Wattenberg MM, Asch D, Yu S, et al. Platinum response characteristics of patients with pancreatic ductal adenocarcinoma and a germline BRCA1, BRCA2 or PALB2 mutation. Br J Cancer. 2020;122:333–339.
Park W, Chen J, Chou JF, et al. Genomic methods identify homologous recombination deficiency in pancreas adenocarcinoma and optimize treatment selection. Clin Cancer Res. 2020;26:3239–3247.
Golan T, Hammel P, Reni M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N Engl J Med. 2019;381:317–327.
Reiss KA, Mick R, O’Hara MH, et al. Phase II study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic variant in BRCA1, BRCA2, or PALB2. J Clin Oncol. 2021;39:2497–2505.
Pishvaian MJ, Bender RJ, Halverson D, et al. Molecular profiling of patients with pancreatic cancer: initial results from the know your tumor initiative. Clin Cancer Res. 2018;24:5018–5027.
de Bono J, Mateo J, Fizazi K, et al. Olaparib for metastatic castration-resistant prostate cancer. N Engl J Med. 2020;382:2091–2102.
Sung P, Klein H. Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat Rev Mol Cell Biol. 2006;7:739–750.
Prakash R, Zhang Y, Feng W, et al. Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb Perspect Biol. 2015;7:a016600.
van Wilpe S, Tolmeijer SH, Koornstra RHT, et al. Homologous recombination repair deficiency and implications for tumor immunogenicity. Cancers (Basel). 2021;13:1–19.
Toh M, Ngeow J. Homologous recombination deficiency: cancer predispositions and treatment implications. Oncologist. 2021;26:e1526–e1537.
Gonzalez-Martin A, Pothuri B, Vergote I, et al. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381:2391–2402.
Tung NM, Robson ME, Ventz S, et al. TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol. 2020;38:4274–4282.
Wu J, Lu LY, Yu X. The role of BRCA1 in DNA damage response. Protein Cell. 2010;1:117–123.
Sahin IH, Lowery MA, Stadler ZK, et al. Genomic instability in pancreatic adenocarcinoma: a new step towards precision medicine and novel therapeutic approaches. Exp Rev Gastroenterol Hepatol. 2016;10:893–905.
Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1274–1284.
Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381:2416–2428.
Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. N Engl J Med. 2019;381:2403–2415.
Lowery MA, Kelsen DP, Capanu M, et al. Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma. Eur J Cancer. 2018;89:19–26.
O’Reilly EM, Lee JW, Zalupski M, et al. 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;38:1378–1388.
Yin M, Grivas P, Mortazavi A, et al. ATM mutation is associated with shorter overall survival in relapsed/advanced urothelial cancer. J Clin Oncol. 2019;37:370–370.
Hannan Z, Yu S, Domchek S, et al. Clinical characteristics of patients with pancreatic cancer and pathogenic ATM alterations. JNCI Cancer Spectrum. 2021;5:pkaa121.
Randon G, Fuca G, Rossini D, et al. Prognostic impact of ATM mutations in patients with metastatic colorectal cancer. Sci Rep. 2019;9:2858.
Momtaz P, O’Connor CA, Chou JF, et al. Pancreas cancer and BRCA: a critical subset of patients with improving therapeutic outcomes. Cancer. 2021;127:4393–4402.
Cheng HH, Pritchard CC, Boyd T, et al. Biallelic inactivation of BRCA2 in platinum-sensitive metastatic castration-resistant prostate cancer. Eur Urol. 2016;69:992–995.