Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): A multicentre, open-label, phase 2a, multiple basket study Journal Article
| Authors: | Javle, M.; Borad, M. J.; Azad, N. S.; Kurzrock, R.; Abou-Alfa, G. K.; George, B.; Hainsworth, J.; Meric-Bernstam, F.; Swanton, C.; Sweeney, C. J.; Friedman, C. F.; Bose, R.; Spigel, D. R.; Wang, Y.; Levy, J.; Schulze, K.; Cuchelkar, V.; Patel, A.; Burris, H. |
| Article Title: | Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): A multicentre, open-label, phase 2a, multiple basket study |
| Abstract: | Background: Systemic therapies for metastatic biliary tract cancers are few, and patients have a median overall survival of less than 1 year. MyPathway evaluates the activity of US Food and Drug Administration-approved therapies in non-indicated tumours with potentially actionable molecular alterations. In this study, we present an analysis of patients with metastatic biliary tract cancers with HER2 amplification, overexpression, or both treated with a dual anti-HER2 regimen, pertuzumab plus trastuzumab, from MyPathway. Methods: MyPathway is a non-randomised, multicentre, open-label, phase 2a, multiple basket study. Patients aged 18 years and older with previously treated metastatic biliary tract cancers with HER2 amplification, HER2 overexpression, or both and an Eastern Cooperative Oncology Group performance status of 0–2 were enrolled from 23 study sites in the USA and received intravenous pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) plus trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks). The primary endpoint was investigator-assessed objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary outcome and adverse events were analysed in all patients who received at least one dose of pertuzumab and trastuzumab. This trial is registered with ClinicalTrials.gov, NCT02091141, and is ongoing. Findings: 39 patients enrolled in the MyPathway HER2 biliary tract cancer cohort between Oct 28, 2014, and May 29, 2019, were evaluable for anti-tumour activity by the March 10, 2020, data cutoff date. Median follow-up was 8·1 months (IQR 2·7–15·7). Nine of 39 patients achieved a partial response (objective response rate 23% [95% CI 11–39]). Grade 3–4 treatment-emergent adverse events were reported in 18 (46%) of 39 patients, most commonly increased alanine aminotransferase and increased aspartate aminotransferase (each five [13%] of 39). Treatment-related grade 3 adverse events were reported in three (8%) of 39 patients, including increased alanine aminotransferase, aspartate aminotransferase, blood alkaline phosphatase, and blood bilirubin. Serious treatment-emergent adverse events were observed in ten (26%) of 39 patients, of which only abdominal pain occurred in more than one patient (two [5%] of 39). There were no treatment-related serious adverse events, treatment-related grade 4 events, or deaths. Interpretation: Treatment was well tolerated in patients with previously treated HER2-positive metastatic biliary tract cancer. The response rate is promising for the initiation of randomised, controlled trials of pertuzumab plus trastuzumab in this patient population. Funding: F Hoffmann-La Roche–Genentech. © 2021 Elsevier Ltd |
| Keywords: | adult; clinical article; human tissue; treatment outcome; treatment response; aged; human cell; fatigue; ascites; drug safety; gastrointestinal hemorrhage; hypertension; side effect; united states; follow up; gene overexpression; metastasis; neutrophil count; phase 2 clinical trial; gene amplification; anemia; nausea; dehydration; peripheral neuropathy; epidermal growth factor receptor 2; cohort analysis; antineoplastic activity; abdominal pain; alanine aminotransferase blood level; aspartate aminotransferase blood level; asthenia; chill; dyspnea; fever; rash; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; bilirubin; hyponatremia; disease severity; multicenter study; urinary tract infection; muscle weakness; peripheral edema; sepsis; aging; pleura effusion; alkaline phosphatase blood level; leukocyte count; trastuzumab; triacylglycerol lipase blood level; bacterial infection; bilirubin blood level; biliary tract cancer; lymphocyte count; small intestine obstruction; appendicitis; cholestasis; pertuzumab; triacylglycerol lipase; abdominal distension; drug-induced liver injury; decreased appetite; device infection; failure to thrive; response evaluation criteria in solid tumors; her2 gene; cholangitis; infusion related reaction; human; male; female; article; ecog performance status; peripheral swelling |
| Journal Title: | Lancet Oncology |
| Volume: | 22 |
| Issue: | 9 |
| ISSN: | 1470-2045 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2021-09-01 |
| Start Page: | 1290 |
| End Page: | 1300 |
| Language: | English |
| DOI: | 10.1016/s1470-2045(21)00336-3 |
| PUBMED: | 34339623 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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