National Surgical Adjuvant Breast and Bowel Project Foundation, Pittsburgh, USA; Houston Methodist Cancer Center, Houston, USA.
Women, Infants Hospital of Rhode Island, Providence, USA.
Ann Oncol. 2022 Apr;33(4):384-394. doi: 10.1016/j.annonc.2022.01.009. Epub 2022 Jan 31.
BACKGROUND: Primary analyses of the phase III BrighTNess trial showed addition of carboplatin with/without veliparib to neoadjuvant chemotherapy significantly improved pathological complete response (pCR) rates with manageable acute toxicity in patients with triple-negative breast cancer (TNBC). Here, we report 4.5-year follow-up data from the trial. PATIENTS AND METHODS: Women with untreated stage II-III TNBC were randomized (2 : 1 : 1) to paclitaxel (weekly for 12 doses) plus: (i) carboplatin (every 3 weeks for four cycles) plus veliparib (twice daily); (ii) carboplatin plus veliparib placebo; or (iii) carboplatin placebo plus veliparib placebo. All patients then received doxorubicin and cyclophosphamide every 2-3 weeks for four cycles. The primary endpoint was pCR. Secondary endpoints included event-free survival (EFS), overall survival (OS), and safety. Since the co-primary endpoint of increased pCR with carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel was not met, secondary analyses are descriptive. RESULTS: Of 634 patients, 316 were randomized to carboplatin plus veliparib with paclitaxel, 160 to carboplatin with paclitaxel, and 158 to paclitaxel. With median follow-up of 4.5 years, the hazard ratio for EFS for carboplatin plus veliparib with paclitaxel versus paclitaxel was 0.63 [95% confidence interval (CI) 0.43-0.92, P = 0.02], but 1.12 (95% CI 0.72-1.72, P = 0.62) for carboplatin plus veliparib with paclitaxel versus carboplatin with paclitaxel. In post hoc analysis, the hazard ratio for EFS was 0.57 (95% CI 0.36-0.91, P = 0.02) for carboplatin with paclitaxel versus paclitaxel. OS did not differ significantly between treatment arms, nor did rates of myelodysplastic syndromes, acute myeloid leukemia, or other secondary malignancies. CONCLUSIONS: Improvement in pCR with the addition of carboplatin was associated with long-term EFS benefit with a manageable safety profile, and without increasing the risk of second malignancies, whereas adding veliparib did not impact EFS. These findings support the addition of carboplatin to weekly paclitaxel followed by doxorubicin and cyclophosphamide neoadjuvant chemotherapy for early-stage TNBC.
背景：III 期 BrighTNess 试验的主要分析显示，卡铂联合/不联合维利帕利添加到新辅助化疗中，可显著提高三阴性乳腺癌（TNBC）患者的病理完全缓解（pCR）率，并具有可管理的急性毒性。在此，我们报告了该试验的 4.5 年随访数据。
患者和方法：未经治疗的 II-III 期 TNBC 患者被随机分为（2：1：1）三组：（i）紫杉醇（每周 12 剂）加：（i）卡铂（每 3 周 4 个周期）加维利帕利（每日 2 次）；（ii）卡铂加维利帕利安慰剂；或（iii）卡铂安慰剂加维利帕利安慰剂。所有患者随后每 2-3 周接受多柔比星和环磷酰胺 4 个周期。主要终点为 pCR。次要终点包括无事件生存（EFS）、总生存（OS）和安全性。由于卡铂联合维利帕利加紫杉醇与卡铂加紫杉醇相比增加 pCR 的共同主要终点未达到，因此次要分析是描述性的。
结果：在 634 名患者中，316 名被随机分配至卡铂联合维利帕利加紫杉醇组，160 名患者被分配至卡铂加紫杉醇组，158 名患者被分配至紫杉醇组。中位随访 4.5 年后，卡铂联合维利帕利加紫杉醇组与紫杉醇组相比，EFS 的风险比为 0.63（95%置信区间[CI]为 0.43-0.92，P=0.02），但卡铂联合维利帕利加紫杉醇组与卡铂加紫杉醇组相比为 1.12（95%CI 为 0.72-1.72，P=0.62）。在事后分析中，卡铂加紫杉醇组与紫杉醇组相比，EFS 的风险比为 0.57（95%CI 为 0.36-0.91，P=0.02）。各治疗组之间的 OS 无显著差异，骨髓增生异常综合征、急性髓系白血病或其他继发性恶性肿瘤的发生率也无显著差异。
结论：添加卡铂可提高 pCR 率，从而带来长期 EFS 获益，且安全性可管理，不会增加二次恶性肿瘤的风险，而添加维利帕利则不会影响 EFS。这些发现支持将卡铂加入每周紫杉醇，随后加入多柔比星和环磷酰胺新辅助化疗，用于早期 TNBC。
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