1. Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study
- Author
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Howard A. Burris, Vaikunth Cuchelkar, Marwan Fakih, Steven Blotner, Ron Bose, Alyssa Stone, Kanwal Pratap Singh Raghav, Razelle Kurzrock, Katja Schulze, David R. Spigel, Mary Beattie, John D. Hainsworth, Herbert Hurwitz, Christopher Sweeney, Robert R. McWilliams, Ari M. Vanderwalde, Charles Swanton, and Funda Meric-Bernstam
- Subjects
Male ,0301 basic medicine ,Subset Analysis ,Oncology ,medicine.medical_specialty ,Receptor, ErbB-2 ,Colorectal cancer ,Antibodies, Monoclonal, Humanized ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Trastuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,medicine ,Humans ,Adverse effect ,Aged ,business.industry ,Gene Amplification ,Middle Aged ,Evaluable Disease ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Female ,Chills ,Pertuzumab ,medicine.symptom ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
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.
- Published
- 2019
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