Gorodnova, T. V., Sokolenko, A. P., Kotiv, K. B., Ivantsov, A. O., Kondratyev, S. V., Berlev, I. V., & Imyanitov, E. N. (2024). Platinum Resistance after Neoadjuvant Chemotherapy. Voprosy Onkologii, 70(1), 82–87. https://doi.org/10.37469/0507-3758-2024-70-1-82-87

Abstract

Introduction. In BRCA1-associated ovarian carcinomas, platinum resistance may occur already during neoadjuvant chemotherapy due to selection and repopulation of cells with reduced or partially preserved DNA mismatch repair function. The use of platinum-free adjuvant chemotherapy (ACT) in patients without loss of BRCA1 heterozygosity in residual tumor (noLOH) may improve the outcomes of combination treatment for patients with advanced ovarian cancer. Aim. To analyze the results of using platinum-free ACT based on the doxorubicin and paclitaxel (AT) regimen in patients without loss of BRCA1 heterozygosity in the residual tumor within the framework of a prospective randomized trial.

Materials and Methods. The prospective clinical trial NCT04747717 included 22 patients in the mitomycin C and cisplatin (MP) group and 15 patients randomized to the group with paclitaxel and carboplatin (TCbP) standart of treatment. Two patients from the MP group received a combination of AT in the adjuvant regimen.

Results. MR group showed restoration of BRCA1 heterozygosity in the residual tumor tissue in 5/18 (28 %) patients, whereas in TCbP group, BRCA1 noLOH status was observed in 3/10 (30 %) patients. Both patients who were treated with the adjuvant platinum-free AT regimen were in clinical remission of 41 and 17 months at the time of outcome assessment.

Conclusion. Switching chemotherapy in the postoperative period to platinum-free regimens in patients with changes in LOH status is a promising approach to the treatment of BRCA1-associated ovarian carcinomas.

https://doi.org/10.37469/0507-3758-2024-70-1-82-87

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References

Salgia R., Kulkarni P. The genetic/non-genetic duality of drug 'resistance' in cancer. Trends Cancer. 2018; 4(2): 110-118.-DOI: https://doi.org/10.1016/j.trecan.2018.01.001.

Chatterjee N., Bivona T.G. Polytherapy and targeted cancer drug resistance. Trends Cancer. 2019; 5(3): 170-182.-DOI: https://doi.org/10.1016/j.trecan.2019.02.003.

Cecere S., Giannone G., Salutari V., et al. Olaparib as maintenance therapy in patients with BRCA 1-2 mutated recurrent platinum sensitive ovarian cancer: Real world data and post progression outcome. Gynecol Oncol. 2020; 156(1): 38-44.-DOI: https://doi.org/10.1016/j.ygyno.2019.10.023.

Lord C.J., Ashworth A. Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat Med. 2013; 19(11): 1381-8.-DOI: https://doi.org/10.1038/nm.3369.

Markman M., Rothman R., Hakes T., et al. Second-line platinum therapy in patients with ovarian cancer previously treated with cisplatin. J Clin Oncol. 1991: 389-393.-DOI: https://doi.org/10.1200/JCO.1991.9.3.389.

Colombo N., Sessa C., du Bois A., et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent diseasedagger. Ann Oncol. 2019; 30(5): 672-705.-DOI: https://doi.org/10.1093/annonc/mdz062.

Sokolenko A., Bizin I., Preobrazhenskaya E.V., et al. Molecular profiles of BRCA1-associated ovarian cancer treated by platinum-based therapy: Analysis of primary, residual and relapsed tumors. Int J Cancer. 2020; 146: 1879-88.-DOI: https://doi.org/10.1002/ijc.32776.

Sokolenko A., Preobrazhenskaya E., Marchetti C., et al. Origin of residual tumor masses in BRCA1/2-driven ovarian carcinomas treated by neoadjuvant chemotherapy: selection of preexisting BRCA1/2-proficient tumor cells but not the gain of second ORF-restoring mutation. Pathobiology. 2023; 30(5): 1015-2008.-DOI: https://doi.org/10.1159/000533591.

Aleksakhina S., Kashyap A., Imyanitov E. Mechanisms of acquired tumor drug resistance. Biochim Biophys Acta Rev Cancer. 2019; 1872(2): 188310.-DOI: https://doi.org/10.1016/j.bbcan.2019.188310.

Gorodnova T., Sokolenko A., Kotiv H., et al. A prospective randomized study to evaluate the effectiveness of the mitomycin C and cisplatin (MP) regimen in comparison with standard first-line chemotherapy in patients with advanced BRCA1/2-associated ovarian cancer (NCT04747717). Voprosy Onkologii = Problems in Oncology. 2022; 68(5): 628-638.-DOI: https://doi.org/10.37469/0507-3758-2022-68-5-628-638.

Querleu D., Planchamp F., Chiva L., et al. European Society of Gynaecological Oncology (ESGO) guidelines for ovarian cancer surgery. Int J Gynecol Cancer. 2017; 27: 1534-1542.-DOI: https://doi.org/10.1097/IGC.0000000000001041.

Böhm S., Faruqi A., Said I., et al. Chemotherapy response score: Development and validation of a system to quantify histopathologic response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. J Clin Oncol. 2015; 33: 2457-2463.-DOI: https://doi.org/10.1200/JCO.2014.60.5212.

Gorodnova T.V., Sokolenko A.P., Kotiv Kh.B., et al. Acquired platinum resistance of BRCA1-associated ovarian cancer after neoadjuvant chemotherapy. Doctor.Ru. 2022; 21(5): 87-91.-DOI: https://doi.org/10.31550/1727-2378-2022-21-5-87-91.

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