Trial reportInvestigational new drugs2014
Multi-drug inhibition of the HER pathway in metastatic colorectal cancer: results of a phase I study of pertuzumab plus cetuximab in cetuximab-refractory patients.
Trial report in Investigational new drugs, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 63 citations in OpenAlex.
- First-in-human trial exploring safety, antitumor activity, and pharmacokinetics of Sym013, a recombinant pan-HER antibody mixture, in advanced epithelial malignancies.Investigational new drugs · 2022Trial
- Trial
- Recent clinical advances in nonconjugated antibodies and antibody-drug conjugates for colorectal cancer treatment.Cancer cell international · 2025Review
- Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.World journal of gastroenterology · 2023Review
- Recent and Future Strategies to Overcome Resistance to Targeted Therapies and Immunotherapies in Metastatic Colorectal Cancer.Journal of clinical medicine · 2022Review
- Beyond RAS and BRAF: HER2, a New Actionable Oncotarget in Advanced Colorectal Cancer.International journal of molecular sciences · 2021Review
- Prevalence, prognosis and predictive status of HER2 amplification in anti-EGFR-resistant metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Lattice complex assembled by noncompetitive anti-EGFR antibodies regulates actin cytoskeletal reorganization.Cancer cell international · 2020Article
- Dual HER2 inhibition strategies in the management of treatment-refractory metastatic colorectal cancer: History and status.World journal of clinical cases · 2018Review
- Targeting HER2 in colorectal cancer: The landscape of amplification and short variant mutations in ERBB2 and ERBB3.Cancer · 2018Article
- Dual "mAb" HER family blockade in head and neck cancer human cell lines combined with photon therapy.Scientific reports · 2017Article
- Pharmacogenomics of Targeted Agents for Personalization of Colorectal Cancer Treatment.International journal of molecular sciences · 2017Review
- ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC.PloS one · 2017Article
- LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.Cancer chemotherapy and pharmacology · 2017Article
- HER-2 inhibition in gastric and colorectal cancers: tangible achievements, novel acquisitions and future perspectives.Oncotarget · 2016Review
- Oncogenic fingerprint of epidermal growth factor receptor pathway and emerging epidermal growth factor receptor blockade resistance in colorectal cancer.World journal of clinical oncology · 2016Review
- The Multidisciplinary Management of Colorectal Cancer: Present and Future Paradigms.Clinics in colon and rectal surgery · 2016Review
- Article
- The anti-HER3 antibody patritumab abrogates cetuximab resistance mediated by heregulin in colorectal cancer cells.Oncotarget · 2014Article
- Current approaches for predicting a lack of response to anti-EGFR therapy in KRAS wild-type patients.BioMed research international · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 1 country.
Funding
Abstract
purposeResistance to cetuximab, a monoclonal antibody against the epithelial growth factor receptor (EGFR), in colorectal cancer (CRC) may result from compensatory signaling through ErbB receptors, ErbB2/neu/HER2 (HER2) and ErbB3/HER3 (HER3). Pertuzumab is a monoclonal antibody that blocks HER2 hetero-dimerization; thus the combination of pertuzumab and cetuximab could possibly overcome cetuximab resistance. PATIENTS AND
methodsThis single-arm, open-label, multicenter phase I/II study was designed to assess the safety and efficacy of pertuzumab and cetuximab in patients with cetuximab-resistant KRAS wild type metastatic CRC. Thirteen patients were enrolled and received cetuximab in combination with pertuzumab at several dose levels in a 3 + 3 design. Patients were assessed for dose-limiting toxicity (DLT) during the first cycle. A phase II portion was planned, but not initiated due to toxicity.
resultsSix of the thirteen patients (46 %) experienced DLTs, therefore the study was terminated early. Grade 3 or higher DLTs included dermatitis with desquamation and/or acneiform rash (n = 6), mucositis or stomatitis (n = 5), and diarrhea (n = 2). There was one Grade 5 event (myocardial infarction) attributed to underlying disease. Among the 13 patients, seven (54 %) were evaluable for response. The objective response rate was 14 %: one patient had a partial response lasting 6 months. Two patients had stable disease (29 %), and four had progressive disease (57 %). Median progression free survival was 2.1 months (95 % CI, 1.5-4.9) and median overall survival was 3.7 months (95 % CI, 1.6-7.9).
conclusionCombination pertuzumab and cetuximab in refractory CRC was associated with potential antitumor activity; however, the combination was not tolerable due to overlapping toxicities.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.