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☆

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.

Keywords: HER2-positive breast cancer; KAMILLA; T-DM1; brain metastases; metastatic breast cancer; trastuzumab emtansine.

Conflict of interest statement

Disclosure FM declares serving on speakers' bureaus for F. Hoffmann-La Roche, Novartis, AstraZeneca, Eli Lilly, and Pfizer; and receiving travel grants from F. Hoffmann-La Roche. SD declares grants from F. Hoffmann-La Roche/Genentech during the conduct of the study and grants from Pfizer, Novartis, AstraZeneca, Lilly, Puma, Myriad, Orion, Amgen, Sanofi, Genomic Health, GE, Servier, Merck Sharp & Dohme, and Bristol Myers Squibb outside of the submitted work; non-financial support from Pfizer, AstraZeneca, and F. Hoffmann-La Roche/Genentech; and personal fees from AstraZeneca. CHB declares honoraria from Novartis, F. Hoffmann-La Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, and Eisai; receiving research funding from Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, F. Hoffmann-La Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, Abbvie, Astellas Pharma, Biomarin, Bristol Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Science, Asana Biosciences, Medivation, Daiichi Sankyo, Exelixis, ImClone Systems, LEO Pharma, and Millennium; and reports serving as a consultant/advisor for Boehringer Ingelheim, F. Hoffmann-La Roche/Genentech, Novartis, Astellas Pharma, GlaxoSmithKline, Eisai, and Pfizer. RW reports serving as a consultant/advisor to and receiving research funding from F. Hoffmann-La Roche. AA reports serving as a consultant/advisor for Bayer Hispania. EB declares personal fees from Pfizer, F. Hoffmann-La Roche, Bristol Myers Squibb, Mylan, Clinigen, G1 Therapeutics, TLC PharmaChem, Samsung, and non-financial support from F. Hoffmann-La Roche, Pierre Fabre, Novartis, Pfizer, and AstraZeneca. TH declares institutional grants from F. Hoffmann-La Roche Sweden and Pfizer, travel grants from F. Hoffman-La Roche Sweden, and serving as an advisor to Pfizer Sweden. CMK reports receiving conference and travel expenses from Pfizer and Bristol Myers Squibb. CP-M is an employee of F. Hoffmann-La Roche. MY is an employee of and owns stock in F. Hoffmann-La Roche. MD is an employee of F. Hoffmann-La Roche and owns stock in Novartis. All authors received non-financial support from F. Hoffmann-La Roche in the form of medical writing support for this manuscript. PE has declared no conflicts of interest. Data sharing Qualified researchers may request access to de-identified patient level data through the Clinical Study Data Request platform (www.clinicalstudydatarequest.com) and will be provided with accompanying clinical study documentation (protocol and any associated amendments, annotated case report form, reporting and analysis plan, dataset specifications, and the clinical study report). Researchers requesting access to clinical study documentation only can do so via the following link: http://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing/clinical_study_documents_request_form.htm. Documents are made available on application, per scope and timing criteria as published on the Clinical Study Data Request platform.

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