三阴性乳腺癌的雌激素受体、孕激素受体、人类表皮生长因子受体HER2均为阴性，对内分泌治疗或HER2靶向治疗无效，术前新辅助治疗和术后辅助治疗仍以化疗为主。大约六分之一的三阴性乳腺癌患者术前新辅助化疗标准方案多西他赛＋表柔比星可能获得病理完全缓解。将顺铂或卡铂加入新辅助化疗标准方案，可能提高病理完全缓解率。洛铂是第三代铂类，与第一代顺铂和第二代卡铂相比，抗肿瘤活性较强且毒性较低，已被批准用于治疗晚期乳腺癌等恶性肿瘤。2018年，英国《自然》旗下《自然通讯》发表陆军军医大学西南医院的研究报告，首次证实洛铂可显著提高三阴性早期乳腺癌术前多西他赛＋表柔比星新辅助化疗的病理完全缓解率和客观缓解率。
2022年6月24日，英国《肿瘤内科治疗进展》在线发表陆军军医大学西南医院（第三军医大学第一附属医院）阎文婷、吴秀娟、王姝姝、何澄、钟玲、唐鹏、任林、张婷、姜军、齐晓伟、张毅等学者的论文，报告了三阴性早期乳腺癌术前多西他赛＋表柔比星±洛铂新辅助化疗的五年随访结果。
该单中心非盲随机对照二期临床研究于2014年1月2日～2019年8月19日入组年龄≥18岁且美国东部肿瘤学协作组体力状态评分为0或1的临床I～III期三阴性乳腺癌治疗前可手术患者200例，按1∶1的比例随机分为两组，术前12周每3周给予新辅助化疗，其中101例给予多西他赛75mg/m²＋表柔比星80mg/m²，其余99例给予多西他赛75mg/m²＋表柔比星80mg/m²＋洛铂30mg/m²，术后6周每3周分别给予相同方案辅助化疗。主要终点为总体（乳房＋腋窝）病理完全缓解率和客观（完全＋部分）缓解率，次要终点为无病生存（随机化至疾病进展首次放射影像记录）、总生存和长期安全性。
结果，中位随访48.2个月（四分位：31.1～60.0个月）。
多西他赛＋表柔比星＋洛铂与多西他赛＋表柔比星相比：
病理完全缓解率显著较高：41.4%比17.8%（P<0.001）
浸润癌或死亡率显著较低：10.1%比19.8%（风险比：0.44，95%置信区间：0.21～0.90，P=0.028）
总死亡率较低：7.1%比13.9%（风险比：0.44，95%置信区间：0.18～1.02，P=0.061）
客观缓解率显著较高：92.9%比74.3%（P=0.001）
Ⅲ～Ⅳ级贫血发生率显著较高：52.5%比12.5%（P<0.001）
Ⅲ～Ⅳ级血小板减少发生率显著较高：35.4%比3.1%（P<0.001）
未见洛铂相关死亡或长期毒性风险增加。
因此，该单中心小样本研究五年随访结果表明，洛铂可显著提高三阴性早期乳腺癌术前多西他赛＋表柔比星新辅助治疗的病理完全缓解率和客观缓解率，五年浸润癌或死亡率显著较低、总死亡率较低，非血液学不良反应可耐受，故有必要进一步开展多中心大样本随机对照三期临床研究进行验证。
Ther Adv Med Oncol. 2022 Jun 24;14:17588359221107111.Lobaplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: a 5-year follow-up of a randomized, open-label, phase II trial.Yan W, Wu X, Wang S, He C, Zhong L, Tang P, Ren L, Zhang T, Qi X, Zhang Y.Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.PURPOSE: We report the 5-year follow-up findings of a randomized, open-label, phase II trial of lobaplatin-based neoadjuvant chemotherapy plus adjuvant therapy for triple-negative breast cancer (TNBC).PATIENTS AND METHODS: This study included patients aged ≥18 years with untreated, operable stage I-III TNBC and an Eastern Cooperative Oncology Group performance status of 0 or 1. One group of patients (TE group, n = 99) received four cycles of docetaxel (T, 75 mg/m2) plus epirubicin (E, 80 mg/m2) every 3 weeks, and another group (TEL group, n = 101) received the same treatment with the addition of lobaplatin (L, 30 mg/m2). Two cycles of the corresponding treatments were administered after surgery in both groups. The primary endpoints were total pathological complete response (tpCR) rate and overall response rate (ORR), and the secondary endpoints were disease-free survival, overall survival, and long-term safety. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-14005019).RESULTS: The median follow-up was 48.2 months (interquartile range: 31.1-60.0). The tpCR rate was 41.4% and 17.8% in the TEL group and TE group, respectively (p < 0.001). The HR for comparison of DFS between the TEL group and TE group was 0.44 (95% CI: 0.21-0.90, P p = 0.028). The addition of lobaplatin resulted in an HR of 0.44 (95% CI: 0.18-1.02, P = 0.061) for the difference in OS between the two groups. The ORR, which included complete response and partial response, was 92.9% in the TEL group and 74.3% in the TE group (p = 0.001). The TEL group patients were more likely to develop grade III-IV anemia and thrombocytopenia. No lobaplatin-related deaths or increased risk of long-term toxicity was observed.CONCLUSION: Neoadjuvant lobaplatin therapy can improve the tpCR and ORR rates of TNBC with tolerable side effects and have a tendency to improve the long-term survival.KEYWORDS: lobaplatin; neoadjuvant chemotherapy; platinum; prognosis; triple-negative breast cancerDOI: 10.1177/17588359221107111
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