Cutaneous keratoacanthomas/squamous cell carcinomas associated with neutralization of transforming growth factor β by the monoclonal antibody fresolimumab (GC1008)
Open accessAbstract
Fresolimumab is an antibody capable of neutralizing all human isoforms of transforming growth factor beta (TGFβ) and has demonstrated anticancer activity in investigational studies. Inhibition of TGFβ by fresolimumab can potentially result in the development of cutaneous lesions. The aim of this study was to investigate the clinical, histological, and immunohistochemical characteristics of cutaneous neoplasms associated with fresolimumab. Skin biopsies (n = 24) were collected and analyzed from patients (n = 5) with treatment-emergent, cutaneous lesions arising during a phase 1 study of multiple doses of fresolimumab in patients (n = 29) with melanoma or renal cell carcinoma. Blinded, independent histological review and measurements of Ki-67, p53, and HPV integration were performed. Based on central review, four patients developed lesions with histological characteristics of keratoacanthomas, and of these patients, a single case of well-differentiated squamous cell carcinoma was also found. Expression of Ki-67, no evidence of p53 overexpression, and only focal positivity for human papillomavirus RNA by in situ hybridization in 4/18 cases were consistent with these findings. Following completion of fresolimumab, lesions spontaneously resolved. Therefore, benign, reversible keratoacanthomas were the most common cutaneous neoplasms observed, a finding of importance for adverse event monitoring, patient care, and optimization of therapies targeting TGFβ.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Grade 1 or 2 skin rashes have been reported with fresolimumab and M7824 inhibition.
“Additionally, grade 1 or 2 skin rashes have been reported with fresolimumab and M7824 inhibition338,339.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [339]
Current knowledge, primarily derived from clinical trials with galunisertib, fresolimumab, and a bi-specific anti-PDL-1/anti-TGF-β chimeric trap, M7824, indicate that some patients on high drug doses develop sporadic keratoacanthomas.
“Our current knowledge, primarily derived from clinical trials with galunisertib, fresolimumab, and a bi-specific anti-PDL-1/anti-TGF-β chimeric trap, M7824, indicate that some patients on high drug doses develop sporadic keratoacanthomas338,339.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [339]
Clinical trials of M7824 reveal an association with manageable mucosal bleeding attributed to TGF-β blockade.
“Clinical trials of M7824 reveal an association with manageable mucosal bleeding attributed to TGF-β blockade339.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [339]
Clinical studies suggest that M7824 exerts more durable responses than historic responses for anti-PD-L1 monotherapy.
“Clinical studies suggest that M7824 exerts more durable responses than historic responses for anti-PDL-1 monotherapy339.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [339]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 32 · Cited by 145
- Authors
- Lacouture, M. E., Morris, J. C., Lawrence, D. P., Tan, A. R., Olencki, T. E., Shapiro, G. I., Dezube, B. J., Berzofsky, J. A., Hsu, F. J., & Guitart, J.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- National Cancer Institute (US)
- Massachusetts General Hospital (US)
- Rutgers Cancer Institute (US)
- The Ohio State University (US)
- Dana-Farber Cancer Institute (US)
- Beth Israel Deaconess Medical Center (US)
- Northwestern University (US)
- Corresponding author
- Lacouture, Mario E.
- ORCID
- Venue
- Cancer Immunology, Immunotherapy
- Published
- 2015-01-13
- Volume
- 64
- Issue
- 4
- Pages
- 437-446
- ISSN
- 0340-7004 (ISSN-L)
- 1432-0851
- PMC
- PMC6730642
- OpenAlex
- W2054226475
- Cited by
- 145
- References
- 32
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 28 · 2023: 10 · 2022: 15 · 2021: 19 · 2020: 14 · 2019: 7 · 2018: 14 · 2017: 12 · 2016: 8 · 2015: 5
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cancer Immunology Immunotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P30CA008748)
- Topics
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Health Sciences › Medicine › Dermatology › Chemotherapy-related skin toxicity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- keratoacanthoma, squamous cell carcinoma, cutaneous adverse events, TGF-beta inhibition, monoclonal antibodies, Ki-67, p53, HPV integration, melanoma, renal cell carcinoma, spontaneous resolution
- MeSH terms
- Antibodies, Monoclonal, Carcinoma, Squamous Cell, Humans, Keratoacanthoma, Skin, Skin Neoplasms, Biomarkers, Tumor, Tumor Suppressor Protein p53, Transforming Growth Factor beta, Ki-67 Antigen, Antibodies, Monoclonal, Humanized
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
