Long‐Term Survival of De Novo Stage IV Human Epidermal Growth Receptor 2 (HER2) Positive Breast Cancers Treated with HER2‐Targeted Therapy

• Published in: The oncologist (Dayton, Ohio) Vol. 24; no. 3; pp. 313 - 318
• Main Authors: Wong, Yao, Raghavendra, Akshara Singareeka, Hatzis, Christos, Irizarry, Javier Perez, Vega, Teresita, Horowitz, Nina, Barcenas, Carlos H., Chavez‐MacGregor, Mariana, Valero, Vicente, Tripathy, Debu, Pusztai, Lajos, Murthy, Rashmi K.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.03.2019
• Subjects: Breast Cancer; De novo; Human epidermal growth receptor 2; No evidence of disease; Stage IV; Human epidermal growth receptor 2; Breast cancer; Stage IV; No evidence of disease; De novo
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2018-0213

Background An increasing proportion of human epidermal growth receptor 2 (HER2) positive (HER2+) metastatic breast cancer (MBC) is diagnosed as de novo stage IV disease. We hypothesize that a subset of these patients who achieve no evidence of disease (NED) status after multimodality HER2‐targeted treatments may have prolonged progression‐free survival (PFS) and overall survival (OS). Materials and Methods Patients with de novo stage IV, HER2+ MBC (n = 483) diagnosed between 1998 and 2015 were identified at two institutions (Yale and MD Anderson Cancer Centers). Clinical variables, treatment details, and survival outcomes were compared between those who achieved NED and those who did not. Results All patients received trastuzumab, and 20% also received pertuzumab as first‐line therapy. The median OS was 5.5 years (95% confidence interval [Cl]: 4.8–6.2). Sixty‐three patients (13.0%) achieved NED; their PFS and OS rates were 100% and 98% (95% CI: 94.6%–100%), respectively, at 5 years and remained the same at 10 years. For patients with no NED (n = 420), the PFS and OS rates were 12% (95% CI: 4.5%–30.4%) and 45% (95% CI: 38.4%–52.0%) at 5 years and 0% and 4% (95% CI, 1.3%–13.2%) at 10 years, respectively. NED patients more frequently had solitary metastasis (79% vs. 51%, p = .005) and surgery to resect cancer (59% vs. 22%, p ≤ .001). In multivariate analysis, NED status (hazard ratio [HR]: 0.014, p = .0002) and estrogen receptor positive status (HR: 0.72; p = .04) were associated with prolonged OS. Conclusion Among patients with de novo stage IV, HER2+ MBC, those who achieve NED status have a very high PFS and OS. Further randomized studies are required to fully understand the impact of systemic or locoregional therapy on achieving these excellent long‐term outcomes. Implications for Practice In this retrospective review at two institutions, it was demonstrated that 13% of patients with de novo stage IV, human epidermal growth receptor 2 positive metastatic breast cancer achieved no evidence of disease (NED) status with trastuzumab‐based therapy plus/minus local therapies, and these patients had a very high progression‐free survival (100%) and overall survival (98%) at both the 5‐ and 10‐year time points. Achieving NED status may be an important therapeutic goal. However, further randomized studies are required to fully understand the impact of systemic or locoregional therapy on achieving these excellent long‐term outcomes. 摘要 背景。越来越多的人表皮生长受体 2 (HER2) 阳性 (HER2+) 转移性乳腺癌 (MBC) 被诊断为原发 IV 期疾病。我们假设，这些在多模态 HER2 靶向治疗之后实现无肿瘤状态 (NED)的患者中的一部分人可能已经延长了无进展生存 (PFS) 和总生存 (OS)。 材料和方法。我们识别出了在两个机构(耶鲁和 MD 安德森癌症中心)中，在 1998 年至 2015 年期间被诊断为原发 IV 期 HER2+ MBC 的患者 (n = 483)。我们比较了实现 NED 和未实现 NED 的患者之间的临床变量、治疗细节和生存预后。 结果。所有患者均接受曲妥珠单抗治疗，而且，20% 的患者还接受帕妥珠单抗治疗作为一线治疗。中位 OS 为 5.5 年 [95% 置信区间 (Cl):4.8–6.2]。63 名患者 (13.0%) 实现 NED；他们在第 5 年的 PFS 和 OS 率分别为 100% 和 98%(95% CI:94.6%–100%)，并在第 10 年仍然保持不变。对于未实现 NED 的患者 (n = 420)，第 5 年的 PFS 和 OS 率分别为 12%(95% CI:4.5%–30.4%)和 45%(95% CI:38.4%–52.0%)，第 10 年的 PFS 和 OS 率分别为 0% 和 4%(95% CI，1.3%–13.2%)。NED 患者更常发生孤立性转移(79% 与 51%，p = 0.005)和肿瘤切除手术(59% vs. 22%，p ≤ 0.001)。在多变量分析中，NED 状态 [风险比 (HR):0.014，p = .000 2]和雌激素受体阳性状态(HR:0.72；p = 0.04)与延长的 OS 相关。 结论。在原发 IV 期 HER2+ MBC 患者中，实现 NED 状态的患者具有非常高的 PFS 和 OS。为了全面了解系统或局部治疗对实现这些良好的长期预后的影响，需要进一步实施随机研究。 对临床实践的提示:在本次于两个机构中实施的回顾性调查中， 我们证明 13% 的原发 IV 期人表皮生长受体 2 阳性转移性乳腺癌患者通过基于曲妥珠单抗的治疗加/减局部治疗可以实现无肿瘤状态(NED)，而且，这些患者在第 5 年和第 10 年的时间点具有非常高的无进展生存率 (100%) 和总生存率 (98%)。实现 NED 状态可能是一个重要的治疗目标。不过，为了全面了解系统或局部治疗对实现这些良好的长期预后的影响，需要进一步实施随机研究。 This article reports results of a study designed to assess how often patients with stage IV de novo HER2‐positive metastatic breast cancer achieve no evidence of disease with modern anti‐HER2 targeted therapy.