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Lancet Oncol. 2019 Apr;20(4):518-530. doi: 10.1016/S1470-2045(18)30904-5. Epub 2019 Mar 8.

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

Author information

1
Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: fmeric@mdanderson.org.
2
Department of Medicine, Duke University Medical Center, Durham, NC, USA.
3
Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Mayo Clinic, Rochester, MN, USA.
5
Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
6
West Cancer Center, Memphis, TN, USA.
7
Francis Crick Institute, London, UK.
8
Division of Hematology and Oncology, Moores Cancer Center, University of California San Diego, San Diego, CA, USA.
9
Sarah Cannon Research Institute, Nashville, TN, USA; Tennessee Oncology, PLLC, Nashville, TN, USA.
10
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
11
Washington University School of Medicine, St Louis, MO, USA.
12
Genentech Inc, South San Francisco, CA, USA.

Abstract

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.

PMID:
30857956
PMCID:
PMC6781620
[Available on 2020-04-01]
DOI:
10.1016/S1470-2045(18)30904-5

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