Trastuzumab Rechallenge After Lapatinib- and Trastuzumab-Resistant Disease Progression in HER2-Positive Breast Cancer

详细信息    查看全文

• 作者：Kazuhiro Araki¹ ; ² ; ^{kazuhiro.araki@jfcr.or.jp" class="auth_mail" title="E-mail the corresponding author} ; Ippei Fukada¹ ; ² ; Rie Horii³ ; ⁴ ; Shunji Takahashi⁵ ; Futoshi Akiyama³ ; ⁴ ; Takuji Iwase² ; ⁶ ; Yoshinori Ito¹ ; ²
• 关键词：Cancer genomic ; Combination with various chemotherapies ; Continuing multiple anti-HER2 therapies ; Heterogeneity ; Immune system around tumor microenvironments
• 刊名：Clinical Breast Cancer
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：15
• 期：6
• 页码：432-439
• 全文大小：926 K

文摘

Multiple anti-HER2 therapies have improved the outcome for patients with HER2-positive breast cancer. However, optimal management has yet to be established for lapatinib (LAP)- and trastuzumab (Tmab)-resistant disease progression. Data from our institution were reviewed to contribute to the search for best practices.

Patients and Methods

ra0015">Between June 2009 and March 2013, 74 HER2-positive advanced breast cancer (ABC) patients were treated with LAP with capecitabine (LAPCAP). Patients re-treated with Tmab-based chemotherapies were identified, with a focus on baseline characteristics, chemotherapies, and efficacy. The study focused on the clinical outcomes of 50 patients re-treated with Tmab after LAPCAP-resistant disease progression (LAPCAP-PD), with an assessment of tumor response and clinical benefit (CB). Progression-free survival (PFS) was used as a predictive surrogate marker for the efficacy of Tmab rechallenge.

Results

ra0020">All patients were pretreated with Tmab- and LAP-based chemotherapies. At a median follow-up of 7.9 months, PFS was 4.6 months, and overall survival was 33.7 months after LAPCAP-PD. Rechallenges with Tmab-based chemotherapies included gemcitabine (GEM) in 23 patients, vinorelbine in 14, taxanes in 5, endocrine treatments in 2, and others. The CB rate was 32%, including complete response for 1, partial response for 3, and > 6 months of stable disease for 12. Although the median PFS was longer for patients treated with microtubule inhibitors (MTIs) than with GEM, various chemotherapies had different efficacy regardless of whether or not previous LAPCAP had CBs.

Conclusion

ra0025">Tmab rechallenge combined with not only MTIs but also an antimetabolite agent is effective against some LAPCAP-PD HER2-positive ABC.