S'abonner

Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study - 03/04/19

Doi : 10.1016/S1470-2045(18)30904-5 
Funda Meric-Bernstam, ProfMD a, , Herbert Hurwitz, MD b, 1, , Kanwal Pratap Singh Raghav, MD a, Robert R McWilliams, ProfMD c, Marwan Fakih, ProfMD d, Ari VanderWalde, MD e, Charles Swanton, ProfMD f, Razelle Kurzrock, ProfMD g, Howard Burris, MD h, i, Christopher Sweeney, MD j, Ron Bose, MD k, David R Spigel, MD h, i, Mary S Beattie, MD l, Steven Blotner, MS l, Alyssa Stone, BS l, Katja Schulze, PhD l, Vaikunth Cuchelkar, MBBS l, John Hainsworth, MD h, i
a Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA 
b Department of Medicine, Duke University Medical Center, Durham, NC, USA 
c Mayo Clinic, Rochester, MN, USA 
d Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA 
e West Cancer Center, Memphis, TN, USA 
f Francis Crick Institute, London, UK 
g Division of Hematology and Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA, USA 
h Sarah Cannon Research Institute, Nashville, TN, USA 
i Tennessee Oncology, PLLC, Nashville, TN, USA 
j Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA 
k Washington University School of Medicine, St Louis, MO, USA 
l Genentech Inc, South San Francisco, CA, USA 

* Correspondence to: Prof Funda Meric-Bernstam, Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA Prof Funda Meric-Bernstam Department of Investigational Cancer Therapeutics University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Summary

Background

Therapies targeting HER2 have improved clinical outcomes in HER2-positive breast and gastric cancers, and are emerging as potential treatments for HER2-positive metastatic colorectal cancer. MyPathway evaluates the activity of targeted therapies in non-indicated tumour types with potentially predictive molecular alterations. We aimed to assess the activity of pertuzumab and trastuzumab in patients with HER2-amplified metastatic colorectal cancer.

Methods

MyPathway is an ongoing, phase 2a, multiple basket study. Patients in this subset analysis were aged 18 years or older and had treatment-refractory, histologically confirmed HER2-amplified metastatic colorectal cancer with measurable or evaluable disease and an Eastern Cooperative Oncology Group performance status score of 2 or less, enrolled from 25 hospitals or clinics in 16 states of the USA. Patients received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks, intravenously) and trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks, intravenously). The primary endpoint was the proportion of patients who achieved an objective response based on investigator-reported tumour responses. Analyses were done per protocol. This ongoing trial is registered with ClinicalTrials.gov, number NCT02091141.

Findings

Between Oct 20, 2014, and June 22, 2017, 57 patients with HER2-amplified metastatic colorectal cancer were enrolled in the MyPathway study and deemed eligible for inclusionin this cohort analysis. Among these 57 evaluable patients, as of Aug 1, 2017, one (2%) patient had a complete response and 17 (30%) had partial responses; thus overall 18 of 57 patients achieved an objective response (32%, 95% CI 20–45). The most common treatment-emergent adverse events were diarrhoea (19 [33%] of 57 patients), fatigue (18 [32%] patients), and nausea (17 [30%] patients). Grade 3–4 treatment-emergent adverse events were recorded in 21 (37%) of 57 patients, most commonly hypokalaemia and abdominal pain (each three [5%] patients). Serious treatment-emergent adverse events were reported in ten (18%) patients and two (4%) of these adverse events (ie, chills and infusion-related reaction) were considered treatment related. There were no treatment-related deaths.

Interpretation

Dual HER2-targeted therapy with pertuzumab plus trastuzumab is well tolerated and could represent a therapeutic opportunity for patients with heavily pretreated, HER2-amplified metastatic colorectal cancer.

Funding

F Hoffmann-La Roche/Genentech.

Le texte complet de cet article est disponible en PDF.

Plan


© 2019  Elsevier Ltd. Tous droits réservés.
Ajouter à ma bibliothèque Retirer de ma bibliothèque Imprimer
Export

    Export citations

  • Fichier

  • Contenu

Vol 20 - N° 4

P. 518-530 - avril 2019 Retour au numéro
Article précédent Article précédent
  • 10-year performance of four models of breast cancer risk: a validation study
  • Mary Beth Terry, Yuyan Liao, Alice S Whittemore, Nicole Leoce, Richard Buchsbaum, Nur Zeinomar, Gillian S Dite, Wendy K Chung, Julia A Knight, Melissa C Southey, Roger L Milne, David Goldgar, Graham G Giles, Sue-Anne McLachlan, Michael L Friedlander, Prue C Weideman, Gord Glendon, Stephanie Nesci, Irene L Andrulis, Esther M John, Kelly-Anne Phillips, Mary B Daly, Saundra S Buys, John L Hopper, Robert J MacInnis
| Article suivant Article suivant
  • Risk of subsequent primary neoplasms in survivors of adolescent and young adult cancer (Teenage and Young Adult Cancer Survivor Study): a population-based, cohort study
  • Chloe J Bright, Raoul C Reulen, David L Winter, Daniel P Stark, Martin G McCabe, Angela B Edgar, Clare Frobisher, Michael M Hawkins

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

Mon compte


Plateformes Elsevier Masson

Déclaration CNIL

EM-CONSULTE.COM est déclaré à la CNIL, déclaration n° 1286925.

En application de la loi nº78-17 du 6 janvier 1978 relative à l'informatique, aux fichiers et aux libertés, vous disposez des droits d'opposition (art.26 de la loi), d'accès (art.34 à 38 de la loi), et de rectification (art.36 de la loi) des données vous concernant. Ainsi, vous pouvez exiger que soient rectifiées, complétées, clarifiées, mises à jour ou effacées les informations vous concernant qui sont inexactes, incomplètes, équivoques, périmées ou dont la collecte ou l'utilisation ou la conservation est interdite.
Les informations personnelles concernant les visiteurs de notre site, y compris leur identité, sont confidentielles.
Le responsable du site s'engage sur l'honneur à respecter les conditions légales de confidentialité applicables en France et à ne pas divulguer ces informations à des tiers.


Tout le contenu de ce site: Copyright © 2025 Elsevier, ses concédants de licence et ses contributeurs. Tout les droits sont réservés, y compris ceux relatifs à l'exploration de textes et de données, a la formation en IA et aux technologies similaires. Pour tout contenu en libre accès, les conditions de licence Creative Commons s'appliquent.