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三阴性乳腺癌患者免疫治疗后使用三线PARP抑制剂获得长期完全缓解:一例病例报告

Long-term complete response with third-line PARP inhibitor after immunotherapy in a patient with triple-negative breast cancer: a case report.

作者信息

Caputo Roberta, Pagliuca Martina, Pensabene Matilde, Parola Sara, De Laurentiis Michelino

机构信息

Division of Breast Oncology, Istituto Nazionale Tumori - IRCCS - Fondazione G. Pascale, Naples, Italy.

Clinical and Translational Oncology, Scuola Superiore Meridionale (SSM), Naples, Italy.

出版信息

Front Oncol. 2023 Aug 4;13:1214660. doi: 10.3389/fonc.2023.1214660. eCollection 2023.

Abstract

While standard treatment has shown efficacy in patients with breast cancer gene () mutations, recurrence rates are high and additional effective therapies are needed. Olaparib, a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, approved for the treatment of metastatic germline / breast cancer (BC), has demonstrated evidence of a progression-free survival (PFS) benefit, good safety profile, and improved quality of life compared with standard chemotherapy. We here describe the case of a patient with mutated advanced BC and a long history of response to chemotherapy and immunotherapy who received systemic treatment with olaparib. First diagnosed in March 2011 at the age of 38 years with early-stage BC of the right breast, she underwent quadrantectomy plus ipsilateral axillary lymphadenectomy and adjuvant treatments with chemotherapy regimen containing 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by radiotherapy. Five years later, following a contralateral nodule detection leading to left breast quadrantectomy, she received adjuvant systemic treatment with docetaxel plus cyclophosphamide and radiotherapy. Gene testing showed a germline deleterious variant, and she underwent bilateral prophylactic mastectomy and oophorectomy. One year later, skin metastasis and bone infiltrations were detected, and she was started on first-line systemic treatment. The patient was enrolled in the IMpassion131 trial (investigating atezolizumab addition to paclitaxel) but unblinding showed that she was randomized in the placebo arm. She received second-line systemic therapy with LAG525 plus carboplatin (CLAG525B2101 trial) resulting in a PFS of 14 months. At disease progression, she was eligible for systemic third-line therapy with olaparib (300 mg twice daily) and had a complete response after 6 months of therapy and a PFS of 40 months at the time of writing. To the best of our knowledge, this is the first report of a complete response following treatment with third-line systemic olaparib in a long-responding patient and relatively good tolerability and quality of life, pre-treated with both chemotherapy and immunotherapy.

摘要

虽然标准治疗已显示对患有乳腺癌基因()突变的患者有效,但复发率很高,需要额外的有效治疗方法。奥拉帕利是一种聚腺苷二磷酸核糖聚合酶(PARP)抑制剂,已被批准用于治疗转移性生殖系/乳腺癌(BC),与标准化疗相比,它已证明有无进展生存期(PFS)获益、安全性良好且生活质量得到改善的证据。我们在此描述了一名患有突变型晚期BC且对化疗和免疫治疗有长期反应史的患者接受奥拉帕利全身治疗的病例。她于2011年3月首次被诊断出患有右乳早期BC,当时38岁,接受了象限切除术加同侧腋窝淋巴结清扫术,并采用含5-氟尿嘧啶、表柔比星和环磷酰胺(FEC)的化疗方案进行辅助治疗,随后进行了放疗。五年后,在检测到对侧结节后进行了左乳象限切除术,她接受了多西他赛加环磷酰胺的辅助全身治疗和放疗。基因检测显示存在生殖系有害变异,她接受了双侧预防性乳房切除术和卵巢切除术。一年后,检测到皮肤转移和骨浸润,她开始接受一线全身治疗。该患者参加了IMpassion131试验(研究在紫杉醇中添加阿特珠单抗),但揭盲显示她被随机分配到安慰剂组。她接受了LAG525加卡铂的二线全身治疗(CLAG525B2101试验),无进展生存期为14个月。在疾病进展时,她有资格接受奥拉帕利(每日两次,每次300 mg)的三线全身治疗,治疗6个月后完全缓解,在撰写本文时无进展生存期为40个月。据我们所知,这是首例在一名长期有反应且先前接受过化疗和免疫治疗的患者中,三线全身使用奥拉帕利治疗后出现完全缓解、耐受性相对良好且生活质量较好的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59a5/10438988/d3d257886569/fonc-13-1214660-g001.jpg

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