Targeted therapy for advanced solid tumors on the basis of molecular profiles: Results from MyPathway, an open-label, phase IIa multiple basket study
Open accessAbstract
Purpose: Detection of specific molecular alterations in tumors guides the selection of effective targeted treatment of patients with several types of cancer. These molecular alterations may occur in other tumor types for which the efficacy of targeted therapy remains unclear. The MyPathway study evaluates the efficacy and safety of selected targeted therapies in tumor types that harbor relevant genetic alterations but are outside of current labeling for these treatments. Methods: MyPathway ( ClinicalTrials.gov identifier: NCT02091141) is a multicenter, nonrandomized, phase IIa multiple basket study. Patients with advanced refractory solid tumors harboring molecular alterations in human epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. The primary end point is investigator-assessed objective response rate within each tumor-pathway cohort. Results: Between April 1, 2014 and November 1, 2016, 251 patients with 35 different tumor types received study treatment. The efficacy population contains 230 treated patients who were evaluated for response or discontinued treatment before evaluation. Fifty-two patients (23%) with 14 different tumor types had objective responses (complete, n = 4; partial, n = 48). Tumor-pathway cohorts with notable objective response rates included human epidermal growth factor receptor-2–amplified/overexpressing colorectal (38% [14 of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1 V600-mutated non–small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%). Conclusion: The four currently approved targeted therapy regimens in the MyPathway study produced meaningful responses when administered without chemotherapy in several refractory solid tumor types not currently labeled for these agents.
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In the phase 2 MyPathway study, mPFS and mOS were poorer for HER2-positive metastatic colorectal cancer patients with RAS mutations treated with trastuzumab-pertuzumab compared to the RAS wild-type group.
“In the phase 2 MyPathway study, which focused on HER2-positive patients with mCRC, mPFS and mOS were poorer for patients with RAS mutations treated with trastuzumab-pertuzumab compared to the RAS WT group [26].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [26]
RAS mutant patients did not achieve any treatment response with trastuzumab-pertuzumab.
“Furthermore, RAS mutant patients did not achieve any treatment response with trastuzumab-pertuzumab.”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [26]
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Research works printed but not linked: 1
- Bongin Yoo, Alisha Stein, and Mary Beattie, Genentech, South San Francisco; and Razelle Kurzrock, Moores Cancer Center, University of California San Diego, San Diego, CA. Support The MyPathway study was supported by Roche/Genentech. Prior Presentation Presented in part at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2016, San Francisco, CA, January 21-23, 2016; American Society of Clinical Oncology 52nd Annual Meeting, Chicago, IL, June 3-7, 2016; American Society of Clinical Oncology Gastrointestinal Cancers Symposium 2017, San Francisco, CA, January 19-21, 2017; American Society of Clinical Oncology Genitourinary Cancers Symposium 2017, Orlando, FL, February 16-18, 2017; and American Society of Clinical Oncology 53rd Annual Meeting, Chicago, IL, June 2-7, 2017.
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- Authors
- Hainsworth, J. D., Meric-Bernstam, F., Swanton, C., Hurwitz, H., Spigel, D. R., Sweeney, C., Burris, H. A., Bose, R., Yoo, B., Stein, A., Beattie, M., & Kurzrock, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- John D. Hainsworth, David R. Spigel, and Howard A. Burris, Sarah Cannon Research Institute; Tennessee Oncology, Nashville, TN; Funda Meric-Bernstam, University of Texas MD Anderson Cancer Center, Houston, TX; Charles Swanton, Francis Crick Institute, London, United Kingdom; Herbert Hurwitz, Duke University Medical Center, Durham, NC; Christopher Sweeney, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Ron Bose, Washington University School of Medicine, St Louis, MO; Bongin Yoo, Alisha...
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2018-02-20
- Volume
- 36
- Issue
- 6
- Pages
- 536-542
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2783112448
- Cited by
- 506
- References
- 30
- Citations by year
- 2026: 25 · 2025: 39 · 2024: 48 · 2023: 68 · 2022: 68 · 2021: 77 · 2020: 60 · 2019: 64 · 2018: 45 · 2017: 9 · 2016: 2
- FWCI
- 46.30
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-02-01)
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Francis Crick Institute (10169)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- targeted therapy, advanced solid tumors, molecular profiling, HER2, EGFR, BRAF V600 mutation, Hedgehog signaling, pertuzumab, trastuzumab, erlotinib, vemurafenib, vismodegib, refractory cancer, colorectal cancer, non-small cell lung cancer, objective response rate, off-label drug use
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Mutation, Neoplasms, Erb-b2 Receptor Tyrosine Kinases, Proto-Oncogene Proteins B-raf, Hedgehog Proteins, Molecular Targeted Therapy, ErbB Receptors
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