Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB).

Lin, Nancy U.; Murthy, Rashmi Krishna; Anders, Carey K.; Borges, Virginia F.; Hurvitz, Sara A.; Loi, Sherene; Abramson, Vandana G.; Bédard, Philippe L.; Oliveira, Mafalda; Zelnak, Amelia; DiGiovanna, Michael P.; Bachelot, Thomas; Chien, Amy Jo; O’Regan, Ruth; Wardley, Andrew M; Müller, Volkmar; Carey, Lisa A.; McGoldrick, Suzanne; An, Grace; Winer, Eric P.

doi:10.1200/jco.2020.38.15_suppl.1005

Cited by 17 publications

(17 citation statements)

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“…Tucatinib, in combination with trastuzumab and capecitabine, achieved an improvement in PFS (+ 2.2 months) and overall survival (+ 4.5 months) compared to trastuzumab and capecitabine alone 20 . This effect was also seen in patients with brain metastases 33 .…”

Section: Discussionsupporting

confidence: 53%

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine

Laakmann

Emons

Taran

et al. 2020

Geburtshilfe Frauenheilkd

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Purpose Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with a focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the patient characteristics and descriptive prognostic data for HER2-positive patients who have completed a treatment with T-DM1. Therapy patterns after T-DM1 and progression-free survival are reported as well as overall survival. Results A total of 85 patients were identified for the study who were prospectively observed during therapy after the termination of T-DM1. The main reason for T-DM1 termination was progress. Following T-DM1, lapatinib, trastuzumab and chemotherapy were the main therapy choices. Median progression-free survival was 4.8 months (95% CI: 3.2 – 6.3) and median overall survival was 18.4 months (95% CI: 15.5 – 21.3). Conclusions Therapy options after T-DM1 in a real-world setting seem to exhibit a relevant clinical efficacy, supporting the concept of continuous anti-HER2 treatments in the advanced therapy setting for breast cancer patients. Novel therapies are needed to improve the rather short median progression-free survival.

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Section: Discussionsupporting

confidence: 53%

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine

Laakmann

Emons

Taran

et al. 2020

Geburtshilfe Frauenheilkd

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“…In our study, 87% of patients had progressed after radiotherapy, and 70% of HER2-positive patients had prior lapatinib. Furthermore, the CNS ORR we observed also compares favorably with that of neratinib and capecitabine (CNS ORR 49%) and tucatinib-trastuzumab-capecitabine (CNS ORR 47%) [29,30]. For patients with HER2-negative disease, options are substantially more limited.…”

Section: Discussionmentioning

confidence: 64%

Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases

et al. 2020

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Background We aimed to examine the safety and efficacy of bevacizumab and carboplatin in patients with breast cancer brain metastases. Methods We enrolled patients with breast cancer and > 1 measurable new or progressive brain metastasis. Patients received bevacizumab 15 mg/kg intravenously (IV) on cycle 1 day 1 and carboplatin IV AUC = 5 on cycle 1 day 8. Patients with HER2-positive disease also received trastuzumab. In subsequent cycles, all drugs were administered on day 1 of each cycle. Contrast-enhanced brain MRI was performed at baseline, 24–96 h after the first bevacizumab dose (day + 1), and every 2 cycles. The primary endpoint was objective response rate in the central nervous system (CNS ORR) by composite criteria. Associations between germline VEGF single nucleotide polymorphisms (rs699947, rs2019063, rs1570360, rs833061) and progression-free survival (PFS) and overall survival (OS) were explored, as were associations between early (day + 1) MRI changes and outcomes. Results Thirty-eight patients were enrolled (29 HER2-positive, 9 HER2-negative); all were evaluable for response. The CNS ORR was 63% (95% CI, 46–78). Median PFS was 5.62 months and median OS was 14.10 months. As compared with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, patients with ECOG PS 1–2 had significantly worse PFS and OS (all P < 0.01). No significant associations between VEGF genotypes or early MRI changes and clinical outcomes were observed. Conclusions The combination of bevacizumab and carboplatin results in a high rate of durable objective response in patients with brain metastases from breast cancer. This regimen warrants further investigation. Trial registration NCT01004172. Registered 28 October 2009.

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“…Though efficacy of HER2-TKI as a single agent was moderate, combinations of HER2-TKI with capecitabine offered survival benefit for HER2-positive patients with brain metastasis [ 85 , 86 ]. Lapatinib, neratinib, and tucatinib all had successful attempt in this area [ 87 – 89 ].…”

Section: Her2-tkismentioning

confidence: 99%

Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001–2020)

Huang¹,

Jiang²

2020

J Hematol Oncol

284

169

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Tyrosine kinases are implicated in tumorigenesis and progression, and have emerged as major targets for drug discovery. Tyrosine kinase inhibitors (TKIs) inhibit corresponding kinases from phosphorylating tyrosine residues of their substrates and then block the activation of downstream signaling pathways. Over the past 20 years, multiple robust and well-tolerated TKIs with single or multiple targets including EGFR, ALK, ROS1, HER2, NTRK, VEGFR, RET, MET, MEK, FGFR, PDGFR, and KIT have been developed, contributing to the realization of precision cancer medicine based on individual patient’s genetic alteration features. TKIs have dramatically improved patients’ survival and quality of life, and shifted treatment paradigm of various solid tumors. In this article, we summarized the developing history of TKIs for treatment of solid tumors, aiming to provide up-to-date evidence for clinical decision-making and insight for future studies.

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Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB).

Cited by 17 publications

References 0 publications

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine

Treatment Landscape and Prognosis After Treatment with Trastuzumab Emtansine

Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases

Tyrosine kinase inhibitors for solid tumors in the past 20 years (2001–2020)

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