MaltSci 麦伴科研

Appearance

Curated Papers > In recent years, high-impact research on "brain-computer interfaces" (IF≥30, last 5 years)

Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆. ​

Literature Information ​

DOI10.1016/j.annonc.2020.06.020
PMID32634611
JournalAnnals of oncology : official journal of the European Society for Medical Oncology
Impact Factor65.4
JCR QuartileQ1
Publication Year2020
Times Cited188
KeywordsHER2-positive breast cancer, KAMILLA, T-DM1, brain metastases, metastatic breast cancer
Literature TypeClinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't
ISSN0923-7534
Pages1350-1358
Issue31(10)
AuthorsF Montemurro, S Delaloge, C H Barrios, R Wuerstlein, A Anton, E Brain, T Hatschek, C M Kelly, C Peña-Murillo, M Yilmaz, M Donica, P Ellis

TL;DR ​

The KAMILLA study evaluates the efficacy of trastuzumab emtansine (T-DM1) in patients with HER2-positive breast cancer and brain metastases, revealing a best overall response rate of 21.4% and clinical benefit rate of 42.9% among those with measurable brain metastases. These findings suggest that T-DM1 is both active and well-tolerated in this challenging patient population, warranting further investigation.

Search for more papers on MaltSci.com ​

HER2-positive breast cancer · KAMILLA · T-DM1 · brain metastases · metastatic breast cancer

Abstract ​

BACKGROUND Patients with brain metastases (BM) from human epidermal growth factor receptor 2 (HER2)-positive breast cancer represent a difficult-to-treat population. Trastuzumab emtansine (T-DM1) has shown potential activity in this subset of patients in small clinical series.

PATIENTS AND METHODS KAMILLA is an ongoing, phase IIIb study of T-DM1 in patients with HER2-positive locally advanced/metastatic breast cancer with prior HER2-targeted therapy and chemotherapy. Patients received T-DM1 3.6 mg/kg every 3 weeks (intravenously) until unacceptable toxicity, withdrawal of consent, or disease progression. Tumor response and clinical outcomes in patients with baseline BM were evaluated in this post hoc, exploratory analysis. The main outcome measures were best overall response rate (complete response + partial response) and clinical benefit rate (complete response + partial response + stable disease lasting ≥6 months) by RECIST v1.1 criteria, progression-free survival, overall survival, and safety.

RESULTS Of 2002 treated patients, 398 had baseline BM. In 126 patients with measurable BM, the best overall response rate and clinical benefit rate were 21.4% [95% confidence interval (CI) 14.6-29.6] and 42.9% (95% CI 34.1-52.0), respectively. A reduction in the sum of the major diameters of BM ≥30% occurred in 42.9% (95% CI 34.1-52.0), including 49.3% (95% CI 36.9-61.8) of 67 patients without prior radiotherapy to BM. In the 398 patients with baseline BM, median progression-free survival and overall survival were 5.5 (95% CI 5.3-5.6) months and 18.9 (95% CI 17.1-21.3) months, respectively. The adverse event profile was broadly similar in patients with and without baseline BM, although nervous system adverse events were more common in patients with [208 (52.3%)] versus without [701 (43.7%)] baseline BM.

CONCLUSION This exploratory analysis of patients with HER2-positive metastatic breast cancer and BM enrolled in a prospective clinical trial shows that T-DM1 is active and well-tolerated in this population. T-DM1 should be explored further in this setting.

TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01702571.

MaltSci.com AI Research Service ​

Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining

Primary Questions Addressed ​

  1. What are the long-term effects of T-DM1 on patients with HER2-positive breast cancer and brain metastases compared to other treatment options?
  2. How does the presence of brain metastases influence the overall survival rates in patients treated with T-DM1?
  3. What specific adverse events are most commonly associated with T-DM1 in patients with brain metastases, and how do they compare to those without?
  4. What are the implications of the clinical benefit rate findings for future treatment strategies in HER2-positive breast cancer patients with brain metastases?
  5. How might the results of the KAMILLA trial influence the design of future clinical trials targeting brain metastases in HER2-positive breast cancer?

Key Findings ​

1. Background and Purpose: Patients with brain metastases (BM) from HER2-positive breast cancer represent a particularly challenging group to treat due to the aggressive nature of the disease and the limited efficacy of standard treatments in this subset. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate, has shown promising activity in earlier small clinical series for patients with HER2-positive breast cancer, including those with BM. The KAMILLA study is a phase IIIb clinical trial aimed at assessing the efficacy and safety of T-DM1 in patients with HER2-positive locally advanced or metastatic breast cancer who have previously undergone HER2-targeted therapy and chemotherapy. This exploratory final analysis of cohort 1 specifically focuses on patients with baseline brain metastases.

2. Main Methods and Findings: In the KAMILLA study, 2002 patients were treated with T-DM1 at a dosage of 3.6 mg/kg every three weeks. Among these, 398 patients had existing BM at baseline, and 126 of these had measurable BM. The primary outcome measures included best overall response rate (BORR) and clinical benefit rate (CBR), as well as progression-free survival (PFS) and overall survival (OS). The analysis revealed that the best overall response rate was 21.4%, and the clinical benefit rate was 42.9%. Notably, a reduction of 30% or more in the sum of the diameters of BM was observed in 42.9% of patients, with a higher response (49.3%) noted among those who had not received prior radiotherapy. The median PFS was 5.5 months, and the median OS was 18.9 months. Adverse events were similar between patients with and without BM, although nervous system-related adverse events were more prevalent in the BM group.

3. Core Conclusions: The exploratory analysis demonstrates that T-DM1 is both active and well-tolerated in patients with HER2-positive metastatic breast cancer and BM. The observed response rates and survival outcomes suggest that T-DM1 can be an effective therapeutic option for this difficult-to-treat population. The safety profile is acceptable, although careful monitoring for nervous system adverse effects is warranted.

4. Research Significance and Impact: This study contributes critical insights into the treatment landscape for HER2-positive breast cancer patients with brain metastases, highlighting T-DM1 as a viable therapeutic strategy. Given the limited options available for this patient population, the findings underscore the need for further exploration of T-DM1 in clinical settings. This research may influence clinical practice guidelines and encourage additional studies to optimize treatment protocols for patients with brain metastases, ultimately aiming to improve outcomes in this challenging subgroup.

Literatures Citing This Work ​

  1. Management of Brain and Leptomeningeal Metastases from Breast Cancer. - Alessia Pellerino;Valeria Internò;Francesca Mo;Federica Franchino;Riccardo Soffietti;Roberta Rudà - International journal of molecular sciences (2020)
  2. HER2-targeted therapy prolongs survival in patients with HER2-positive breast cancer and intracranial metastatic disease: a systematic review and meta-analysis. - Anders W Erickson;Farinaz Ghodrati;Steven Habbous;Katarzyna J Jerzak;Arjun Sahgal;Manmeet S Ahluwalia;Sunit Das - Neuro-oncology advances (2020)
  3. The incidence of brain metastases among patients with metastatic breast cancer: a systematic review and meta-analysis. - Markus Kuksis;Yizhuo Gao;William Tran;Christianne Hoey;Alex Kiss;Adam S Komorowski;Aman J Dhaliwal;Arjun Sahgal;Sunit Das;Kelvin K Chan;Katarzyna J Jerzak - Neuro-oncology (2021)
  4. Clinical implications of plasma ctDNA features and dynamics in gastric cancer treated with HER2-targeted therapies. - Cheng Zhang;Zuhua Chen;Xiaoyi Chong;Yang Chen;Zhenghang Wang;Ruoying Yu;Tingting Sun;Xiaoxi Chen;Yang Shao;Xiaotian Zhang;Jing Gao;Lin Shen - Clinical and translational medicine (2020)
  5. "Triple-Negative Breast Cancer Central Nervous System Metastases From the Laboratory to the Clinic". - Alexandra S Zimmer - Cancer journal (Sudbury, Mass.) (2021)
  6. Breast Cancer Brain Metastasis-Overview of Disease State, Treatment Options and Future Perspectives. - Chikashi Watase;Sho Shiino;Tatsunori Shimoi;Emi Noguchi;Tomoya Kaneda;Yusuke Yamamoto;Kan Yonemori;Shin Takayama;Akihiko Suto - Cancers (2021)
  7. Pertuzumab Plus High-Dose Trastuzumab in Patients With Progressive Brain Metastases and HER2-Positive Metastatic Breast Cancer: Primary Analysis of a Phase II Study. - Nancy U Lin;Mark Pegram;Solmaz Sahebjam;Nuhad Ibrahim;Anita Fung;Anna Cheng;Alan Nicholas;Whitney Kirschbrown;Priya Kumthekar - Journal of clinical oncology : official journal of the American Society of Clinical Oncology (2021)
  8. Is there a role for CDK 4/6 inhibitors in breast cancer brain metastases? - Ilana Schlam;Sara M Tolaney - Oncotarget (2021)
  9. Leptomeningeal Metastasis in ER + HER2- Advanced Breast Cancer Patients: A Review of the Cases in a Single Institute Over a 15-year Period. - Junichiro Watanabe;Koichi Mitsuya;Shogo Nakamoto;Hideyuki Harada;Shoichi Deguchi;Nakamasa Hayashi;Yoko Nakasu - Breast cancer research and treatment (2021)
  10. HER2-positive breast cancer and tyrosine kinase inhibitors: the time is now. - Ilana Schlam;Sandra M Swain - NPJ breast cancer (2021)

... (178 more literatures)

© 2025 MaltSci - We reshape scientific research with AI technology