Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations
Cite this dataset
Almquist, Daniel et al. (2020). Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations [Dataset]. Dryad. https://doi.org/10.5061/dryad.m0cfxpp0g
Abstract
Methods
Study Population/Study Design:
This is a retrospective study which was approved by Mayo Clinic IRB(16-005168). No consent was needed as information was obtain anonymously. This study was conducted in accordance with principles for human experimentation as defined in the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice guidelines. No participating physicians have conflicts of interest to declare. The Mayo Clinic IRB waived the requirement for informed consent since the data was analyzed anonymously. Patients were identified from all three Mayo Clinic campuses (Minnesota, Arizona and Florida). Patients with a diagnosis of metastatic or unresectable cutaneous melanoma or melanoma of unknown primary whose tumors were analyzed with our 50 gene Solid Tumor Targeted Cancer Gene Panel were included. Patients who received an immune checkpoint inhibitor at any point during their treatment course were included. However, data associated with the first immunotherapy regimen and overall patient outcomes were evaluated for this analysis. Response to targeted therapy, chemotherapy and subsequent lines of immunotherapy treatments were collected but are not the focus of this study. This study allowed for treatment with cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors, PD-1 inhibitors, or combinations that included either a PD-1 inhibitor or CTLA-4 inhibitor.
The objective of this study is to investigate the impact of the presence of CDKN2A mutations (CDKN2Amut), TP53 mutations (TP53mut) and quadruple wild type (QuadWT) mutational status on clinical outcomes in patients who received immune checkpoint inhibitors. Patients who did not carry TP53, CDKN2A, NRAS or BRAFv600 mutations were termed QuadWT. The primary endpoint measured was median time-to-progression (TTP) with secondary endpoints including the percentage of participants without progression at 6 and 12 months, median overall survival (OS), OS at 6 and 12 months, disease control rate (DCR) and overall response rate (ORR) to immunotherapy. Response rates were assessed using available CT or MRI imaging and their associated reports. Calculations were based on the best overall response using the immune related response criteria (irRC) and were categorized as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Pathologic tumor characteristics, patient demographic and clinical details were also collected by chart review.
Genomic Profiling:
The Solid Tumor Targeted Cancer Gene Panel is a 50 gene panel that evaluated the following genes: ABL1, AKT1, ALK, APC, ATM, BRAF, CDH11, CKDN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53 and VHL. This is a laboratory-developed test using Research Use Only reagents. Extracted DNA from the clinical specimen is fragmented, adapter ligated, and a sequence library of fragments is prepared using a custom capture hybridization method. Individual patient samples are indexed for identification and the library is sequenced on an Illumina platform. Sequence data are processed through the Mayo Clinic Clinical Genome Sequencing Lab bioinformatics pipeline and a variant call file is generated for final analysis and reporting(Unpublished Mayo method). This testing is clinically available through Mayo Clinic.
Usage notes
The Solid Tumor Targeted Cancer Gene Panel is a 50 gene panel that evaluated the following genes: ABL1, AKT1, ALK, APC, ATM, BRAF, CDH11, CKDN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53 and VHL. This is a laboratory-developed test using Research Use Only reagents. Extracted DNA from the clinical specimen is fragmented, adapter ligated, and a sequence library of fragments is prepared using a custom capture hybridization method. Individual patient samples are indexed for identification and the library is sequenced on an Illumina platform. Sequence data are processed through the Mayo Clinic Clinical Genome Sequencing Lab bioinformatics pipeline and a variant call file is generated for final analysis and reporting(Unpublished Mayo method). This testing is clinically available through Mayo Clinic.
Funding
None, Award: None