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16 juli 2015: Bron: journal of clinical oncology. Published online before print June 22, 2015, doi: 10.1200/JCO.2015.60.8620

Wanneer borstkankerpatiënten met kleine tumoren en weinig positieve lymfklieren na operatie aanvullend herceptin - trastuzumab krijgen dan hebben zij een langere ziektevrije tijd en grotere kans op overall overleving. Op basis van 8 jaars meting. Dit geldt niet alleen voor hormoon negatieve vormen van borstkanker maar ook, hoewel in iets mindere mate, voor hormoon positieve vormen van borstkanker. Dit blijkt uit een meta analyse van 5 grote gerandomiseerde studies bij totaal ruim 4.250 borstkankerpatiënten.

Voor wie dit nog niet weet herceptin - trastuzumab is een vorm van immuuntherapie. Ik vraag me wel af wat zou er gebeuren als direct na een eerste diagnose gewone immuuntherapie zou worden ingezet via dendritische celtherapie, eventueel met een gemoduleerd virus.

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Patient characteristics by hormone receptor (HR) status. (A) HR-positive tumor categories; (B) HR-positive nodal status; (C) HR-negative tumor categories; (D) HR-negative nodal status. FinHER, Finland Herceptin Study; HERA, Herceptin Adjuvant Study; NSABP, National Surgical Adjuvant Breast and Bowel Project; PACS, Programme Adjuvant Cancer Sein.

Studieresultaten:

de meta-analyse werd gemaakt van 5 gerandomiseerde studies Bijna alle patiënten hadden T1c ziekte, wat betekent dat er bij hun 1e diagnose 1 positieve lymfklier was geconstateerd.

Mediane follow-up van de studie was 8 jaar.

Onder de 2,263 patiënten met hormoon receptor–positieve ziekte, was na 8 jaar het verschil in ziektevrije tijd tussen geen of wel herceptin - trastuzumab respectievelijk 17.3% versus 24.3% (P < .001) en respectievelijk 7.8% versus 11.6% (P = .005) voor overlijden.
De cijfers onder 1,092 hormooon receptor–positieve patienten die maximaal 1 positieve lymfklier hadden waren voor ziektevrije tijd 12.7% versus 19.4% (P = .005) en 5.3% versus 7.4% (P =.12) voor overlijden.
Onder de 1,957 patiënten met hormoon receptor–negatieve ziekte, waren de cijfers na 8 jaar voor ziektevrije tijd respectievelijk 24.0% versus 33.4% (P < .001) en 12.4% versus 21.2% (P < .001) voor overlijden.
Onder de 1,040 hormoon receptor–negatieve patiënten met niet meer dan 1 positieve lymfklier waren de cijfers voor ziektevrije tijd respectievelijk 20.4% versus 26.3% (P = .05) en 8.2% versus 12.2% (P = .084) voor overlijden.

Conclusie van de onderzoekers:

Vrouwen met HER2-positieve tumoren ≤ 2 cm hadden profijt van herceptin - trastuzumab zowel in ziektevrije tijd als in overall overleving. Ook patiënten met hormoon receptor positieve borstkanker met maximaal 1 aangetaste lymfklier kunnen kandidaat zijn voor aanvullend herceptin - trastuzumab. Waardoor deze vrouwen minder agressieve behandelingen nodig hebben.

Het volledige studierapport: Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer and Tumors ≤ 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials is gratis in te zien.

Hier het abstract van de studie

Published online before print June 22, 2015, doi: 10.1200/JCO.2015.60.8620 JCO June 22, 2015 JCO.2015.60.8620

Efficacy of Adjuvant Trastuzumab for Patients With Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer and Tumors ≤ 2 cm: A Meta-Analysis of the Randomized Trastuzumab Trials

+ Author Affiliations

Ciara C. O'Sullivan and Jo Anne Zujewski, National Cancer Institute, Bethesda, MD; Ian Bradbury, Christine Campbell, and Eileen Holmes, Frontier Science, Inverness-shire, Scotland; Marc Spielmann and Suzette Delaloge, Institut de Cancérologie Gustave Roussy, Villejuif, France; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Heikki Joensuu, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Joseph P. Costantino and Priya Rastogi, University of Pittsburgh, Pittsburgh, PA; Dimitrios Zardavas, Breast International Group; Karla V. Ballman, Mayo Clinic, Rochester, MN; Evandro de Azambuja and Martine Piccart-Gebhart, Institut Jules Bordet and L'Université Libre de Bruxelles, Brussels, Belgium; and Richard D. Gelber, Harvard Medical School, Harvard T.H. Chan School of Public Health, Dana-Farber Cancer Institute, and Frontier Science and Technology Research Foundation, Boston, MA.

Corresponding author: Ciara C. O'Sullivan, MD, National Cancer Institute, Room 12N226, 10 Center Dr, Bethesda, MD 20892; e-mail: ciara.o'sullivan@nih.gov.

Abstract

Purpose We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) –positive breast cancer treated in randomized trials.

Methods A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) –positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status.

Results Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively.

Conclusion Women with HER2-positive tumors ≤ 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and ≤ one positive lymph node may be candidates for trials assessing less aggressive treatment approaches.

Footnotes

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.
Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.
Clinical trial information: NCT00045032, ISRCTN76560285., NCT00054587, NCT00004067, NCT00005970

Glossary Terms

DM1:
a derivative of maytansine 1 and a cytotoxic microtubule inhibitor trastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic microtubule inhibitor DM1 and the human epidermal growth factor receptor 2–targeted humanized monoclonal antibody trastuzumab. Also referred to as Kadcyla.
HER2/neu (human epidermal growth factor receptor 2):
also called ErbB2. HER2/neu belongs to the epidermal growth factor receptor (EGFR) family and is overexpressed in several solid tumors. Like EGFR, it is a tyrosine kinase receptor whose activation leads to proliferative signals within the cells. On activation, the human epidermal growth factor family of receptors are known to form homodimers and heterodimers, each with a distinct signaling activity. Because HER2 is the preferred dimerization partner when heterodimers are formed, it is important for signaling through ligands specific for any members of the family. It is typically overexpressed in several epithelial tumors.
lapatinib:
a dual tyrosine kinase inhibitor. Lapatinib has been developed as an inhibitor of the tyrosine kinase activities of ErbB1 (EGFR) and ErbB2. Like other tyrosine kinase inhibitors, it competes with ATP binding to the intracellular regions of the receptors that are activated after tyrosine phosphorylation.
pertuzumab:
a humanized monoclonal antibody that binds to HER2 at a site used by the receptor to form dimers with other receptors (the dimerization site) belonging to this family. Signaling via all HER2 dimers is, therefore, inhibited. Also referred to as Omnitarg. See HER2/neu (human epidermal growth factor receptor 2) and ErbB.
trastuzumab:
a humanized anti-ErbB2 monoclonal antibody approved for treating patients whose breast cancers overexpress the ErbB2 protein or demonstrate ErbB2 gene amplification. It is currently being tested in combination with other therapies.