Pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer (MyPathway): an updated report from a multicentre, open-label, phase 2a, multiple basket study
Published report from the MyPathway trial registered as NCT02091141, in The Lancet Oncology (2019), chosen as the most cited paper whose own text cites the registry id.
Overview
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, at 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.
Indexed on Europe PMC as PubMed record 30857956 (DOI 10.1016/s1470-2045(18)30904-5). Its abstract cites the registry id NCT02091141, which is how it was matched to this trial; no figure has been checked by an editor.
This is the paper Europe PMC returns for registry id NCT02091141 with the most citations, so it is the natural first reading for anyone following the MyPathway trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.