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Clinical Outcomes by Tumor Mutational Burden and Inflammatory Gene Expression With Combined Nivolumab and Ipilimumab or Monotherapy in Advanced Melanoma_CM67-RNASeq

Purpose Exploratory analyses of CheckMate 066 and 067 trials were conducted to investigate associations of tumor mutational burden (TMB), a 4-gene inflammatory gene expression signature, and BRAF mutation status with tumor response, progression-free survival (PFS), and overall survival (OS) in patients with advanced melanoma. Patients and Methods Patients with known programmed death ligand 1 (PD-L1) expression and BRAF mutation status received nivolumab (NIVO) or dacarbazine in CheckMate 066 and either NIVO, ipilimumab (IPI), or NIVO+IPI in CheckMate 067. Whole exome sequencing and RNA sequencing were used to determine TMB and inflammatory gene expression signature scores, respectively. These biomarkers were evaluated in terms of their association with PFS and OS. Results In the NIVO, NIVO+IPI, and IPI arms of CheckMate 067, longer survival was associated with high (> median) versus low (≤ median) TMB with hazard ratios (HRs) (95% confidence interval [CI]) for PFS of 0.45 (0.30–0.65), 0.55 (0.38–0.81), and 0.60 (0.43–0.82), and for OS of 0.46 (0.30–0.71), 0.53 (0.34–0.82), and 0.52 (0.36–0.74), respectively. For NIVO-treated patients, these results were confirmed in CheckMate 066. A survival benefit was observed with high TMB and absence of BRAF mutation. Survival was associated with high versus low inflammatory signature scores with HRs (95% CI) for PFS of 0.56 (0.34–0.94), 0.40 (0.23–0.72), and 0.43 (0.27–0.70), and for OS of 0.37 (0.20–0.66), 0.38 (0.19–0.74), and 0.46 (0.27–0.79), in the NIVO, NIVO+IPI, and IPI arms, respectively. Weak correlations were observed between PD-L1, TMB, and the inflammatory signature. Conclusions Combined assessment of TMB, inflammatory gene expression signature, and BRAF mutation status may be predictive for response to immunotherapy in advanced melanoma.

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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.

Study ID Study Title Study Type
Other

This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.

ID File Type Size Located in
EGAF00004186583 fastq.gz 2.1 GB
EGAF00004186584 fastq.gz 2.2 GB
EGAF00004186585 fastq.gz 2.5 GB
EGAF00004186586 fastq.gz 2.6 GB
EGAF00004186587 fastq.gz 2.5 GB
EGAF00004186588 fastq.gz 2.6 GB
EGAF00004186589 fastq.gz 2.4 GB
EGAF00004186590 fastq.gz 2.5 GB
EGAF00004186591 fastq.gz 2.4 GB
EGAF00004186592 fastq.gz 2.5 GB
EGAF00004186593 fastq.gz 2.2 GB
EGAF00004186594 fastq.gz 2.3 GB
EGAF00004186595 fastq.gz 1.9 GB
EGAF00004186596 fastq.gz 2.1 GB
EGAF00004186597 fastq.gz 2.1 GB
EGAF00004186598 fastq.gz 2.3 GB
EGAF00004186599 fastq.gz 2.2 GB
EGAF00004186600 fastq.gz 2.3 GB
EGAF00004186601 fastq.gz 2.4 GB
EGAF00004186602 fastq.gz 2.5 GB
EGAF00004186603 fastq.gz 2.3 GB
EGAF00004186604 fastq.gz 2.4 GB
EGAF00004186605 fastq.gz 2.3 GB
EGAF00004186606 fastq.gz 2.4 GB
EGAF00004186607 fastq.gz 2.7 GB
EGAF00004186608 fastq.gz 2.8 GB
EGAF00004186609 fastq.gz 2.9 GB
EGAF00004186610 fastq.gz 3.1 GB
EGAF00004186611 fastq.gz 2.1 GB
EGAF00004186612 fastq.gz 2.2 GB
EGAF00004186613 fastq.gz 2.0 GB
EGAF00004186614 fastq.gz 2.1 GB
EGAF00004186615 fastq.gz 2.1 GB
EGAF00004186616 fastq.gz 2.2 GB
EGAF00004186617 fastq.gz 2.7 GB
EGAF00004186618 fastq.gz 2.9 GB
EGAF00004186619 fastq.gz 2.0 GB
EGAF00004186620 fastq.gz 2.2 GB
EGAF00004186621 fastq.gz 2.1 GB
EGAF00004186622 fastq.gz 2.3 GB
EGAF00004186623 fastq.gz 2.3 GB
EGAF00004186624 fastq.gz 2.4 GB
EGAF00004186625 fastq.gz 2.9 GB
EGAF00004186626 fastq.gz 3.2 GB
EGAF00004186627 fastq.gz 2.6 GB
EGAF00004186628 fastq.gz 2.7 GB
EGAF00004186629 fastq.gz 2.3 GB
EGAF00004186630 fastq.gz 2.5 GB
EGAF00004186631 fastq.gz 3.4 GB
EGAF00004186632 fastq.gz 3.5 GB
EGAF00004186633 fastq.gz 2.7 GB
EGAF00004186634 fastq.gz 2.8 GB
EGAF00004186635 fastq.gz 2.5 GB
EGAF00004186636 fastq.gz 2.6 GB
EGAF00004186637 fastq.gz 2.6 GB
EGAF00004186638 fastq.gz 2.7 GB
EGAF00004186639 fastq.gz 2.4 GB
EGAF00004186640 fastq.gz 2.6 GB
EGAF00004186641 fastq.gz 2.3 GB
EGAF00004186642 fastq.gz 2.4 GB
EGAF00004186643 fastq.gz 2.4 GB
EGAF00004186644 fastq.gz 2.5 GB
EGAF00004186645 fastq.gz 2.5 GB
EGAF00004186646 fastq.gz 2.6 GB
EGAF00004186647 fastq.gz 2.6 GB
EGAF00004186648 fastq.gz 2.6 GB
EGAF00004186649 fastq.gz 2.6 GB
EGAF00004186650 fastq.gz 2.6 GB
EGAF00004186651 fastq.gz 2.4 GB
EGAF00004186652 fastq.gz 2.4 GB
EGAF00004186653 fastq.gz 2.7 GB
EGAF00004186654 fastq.gz 2.8 GB
EGAF00004186655 fastq.gz 2.7 GB
EGAF00004186656 1620404679684 2.8 GB
EGAF00004186657 fastq.gz 2.9 GB
EGAF00004186658 fastq.gz 3.0 GB
76 Files (190.0 GB)