^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners

    TEST:
    FoundationOne® CDx

    Company:
    Roche
    Type:
    FDA Approved
    Related tests:
    12d
    Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies. (PubMed, JCO Precis Oncol)
    Numerical differences in the prevalence of MSI-H and GS subtypes were observed between early-stage and late-stage GC. Genomic characteristics of late-stage GC were generally similar between patients of Western and Asian origin.
    Journal • Tumor mutational burden • MSi-H Biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
    |
    TP53 mutation • MSI-H/dMMR • HRD
    |
    FoundationOne® CDx
    13d
    PLATON - Platform for Analyzing Targetable Tumor Mutations (pilot-study) (clinicaltrials.gov)
    P=N/A, N=400, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Trial completion date: Aug 2024 --> Dec 2024
    Trial completion date • Tumor mutational burden • IO biomarker
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    23d
    Mutations in Anaplastic Thyroid Carcinoma: An Analysis of the Japanese National Genomic Database. (PubMed, Laryngoscope Investig Otolaryngol)
    In ATC, PIK3CA, and BRCA2 mutations were associated with a better prognosis, and STK11 mutation was associated with a poorer prognosis in this study. 3.
    Journal • BRCA Biomarker
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • MTAP (Methylthioadenosine Phosphorylase) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • CARD11 (Caspase Recruitment Domain Family Member 11) • NOTCH3 (Notch Receptor 3) • EP300 (E1A binding protein p300) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • MSH3 (MutS Homolog 3)
    |
    TP53 mutation • BRAF mutation • PIK3CA mutation • STK11 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    28d
    Genomic Profiling of Small Cell Neuroendocrine Prostate Cancer and its Implications for Targeted Therapies. (PubMed, Anticancer Res)
    This study is the first to reveal the SCPC genomic landscape in Japanese patients. Although genomic mutations, including DDR mutations, were not predictive of platinum-based chemotherapy efficacy, active genomic testing may improve access to targeted therapies for this challenging malignancy, especially where treatment options are limited.
    Retrospective data • Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • RB1 (RB Transcriptional Corepressor 1) • BRCA (Breast cancer early onset)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • BRCA mutation
    |
    FoundationOne® CDx
    1m
    A Case of Intracranial Mesenchymal Tumor, FET::CREB Fusion-positive, Diagnosed by Genomic Profiling with FoundationOne CDx. (PubMed, NMC Case Rep J)
    Diagnosis of intracranial mesenchymal tumor FET::cyclic adenosine monophosphate response element-binding fusion-positive requires both histological examination and confirmation of the fusion gene. Genomic profiling using the FoundationOne CDx is also useful when the fusion gene cannot be sufficiently confirmed at an individual's institution.
    Journal
    |
    EWSR1 (EWS RNA Binding Protein 1) • FLI1 (Fli-1 Proto-Oncogene ETS Transcription Factor) • ATF1 (Activating Transcription Factor 1)
    |
    FoundationOne® CDx
    1m
    Comprehensive genomic profiling can predict response to neoadjuvant chemotherapy in triple-negative breast cancer. (PubMed, Breast)
    This study suggests that comprehensive CDx testing can be explored as a prognostic tool in early-stage TNBC to predict responses to NACT and disease progression. Based on these results, genomic analysis should be performed early in the patient journey, possibly guiding adjuvant treatment choices and participation in randomized clinical trials, mainly when pCR is not achieved, as the ultimate goal is improving patient outcomes.
    Clinical • Journal • Tumor mutational burden • BRCA Biomarker • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor)
    |
    TP53 mutation • AR positive • TMB-L
    |
    FoundationOne® CDx
    1m
    Genomic Profiling of Extensive Stage Small-Cell Lung Cancer Patients Identifies Molecular Factors Associated with Survival. (PubMed, Lung Cancer (Auckl))
    In ES-SCLC, TMB is associated with worse survival in patients treated with CT alone, and with better survival in patients treated with CT+IO, whether considered as a continuous or a dichotomized variable, at different cut-offs. Alterations in epigenetic factors are also associated to better patient prognosis.
    Journal • Tumor mutational burden • IO biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • KMT2D (Lysine Methyltransferase 2D) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2)
    |
    TP53 mutation • TMB-H • TMB-L
    |
    FoundationOne® CDx
    1m
    Clinical Utility of Liquid-based Comprehensive Genomic Profiling (CGP) in Gastrointestinal Stromal Tumors (GIST). (PubMed, Lab Invest)
    55% (42/77) of liquid samples with a KIT-driver mutation had a co-occurring imatinib-resistant alteration; a minority of cases harbored non-KIT mechanisms of resistance such as FGFR2 fusion, BRAF or EGFR alterations...In conclusion, known driver and TKI-resistant mutations were identified in liquid biopsies of GIST patients with high concordance to tissue in the presence of elevated TF. Liquid biopsy may be valuable in the molecular classification and medical management of GIST.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1)
    |
    FGFR2 mutation • FGFR2 fusion • KIT exon 13 mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    |
    imatinib
    1m
    Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors (clinicaltrials.gov)
    P2, N=50, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2025 --> Dec 2026 | Trial primary completion date: Feb 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    PDGFRA mutation
    |
    FoundationOne® CDx • Guardant360® CDx
    |
    Ayvakit (avapritinib)
    2ms
    Real-world data analysis for factors influencing the quality check status in FoundationOne CDx cancer genomic profiling tests. (PubMed, Sci Rep)
    Of the three factors, percentage of tumor nuclei had the largest effect on quality check status, while the magnitudes of the effects of storage time of FFPE or pancreatic cancer were minor. Collectively, our real-world data indicate that tumor purity is the most important factor for successful CGP, and we would suggest greater than 35% as an ideal percentage of tumor nuclei for CGP submission.
    Clinical • Journal • Real-world evidence
    |
    FoundationOne® CDx
    2ms
    Comprehensive Genome Profiling Test in Japanese Patients With Castration-Resistant Prostate Cancer: A Single-Center Retrospective Study. (PubMed, Cureus)
    The CGP test revealed critical genetic mutations in patients with CRPC and highlighted the poor prognosis associated with CDK12 mutations. The results underscore the necessity for novel therapies tailored to these genetic profiles, emphasizing the role of the CGP in improving treatment personalization.
    Retrospective data • Journal • Tumor mutational burden • PD(L)-1 Biomarker
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • CDK12 (Cyclin dependent kinase 12)
    |
    TP53 mutation • TMB-H • CDK12 mutation
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    2ms
    Tumor mutational burden and survival on immune checkpoint inhibition in >8000 patients across 24 cancer types. (PubMed, J Immunother Cancer)
    Across >8000 patients treated with single-agent ICI, and within individual cancer types with sufficient power, elevated TMB based on the FDA-approved CDx was associated with more favorable rwOS compared with similar patients with lower TMB levels. This biomarker deserves further clinical investigation to potentially guide the use of immunotherapy in expanded clinical contexts.
    Journal • Checkpoint inhibition • Tumor mutational burden • IO Companion diagnostic • PD(L)-1 Biomarker • IO biomarker • PD(L)-1 companion diagnostic
    |
    TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    2ms
    Treatment and reasons for choosing treatment in breast cancer patients who underwent next-generation sequencing test. (PubMed, Oncology)
    The top reasons for patients not receiving the recommended genome-matched therapy were factors related to the patient, including a number of prior treatments higher than what was allowed by the eligibility criteria of the clinical trials, and poor physical condition. Most patients received four or more regimens of cytotoxic chemotherapy before NGS. NGS is only available at the late phase of treatment in Japan, which would constitute a problem for the treatment of breast cancer.
    Journal • Next-generation sequencing • Tumor mutational burden • MSi-H Biomarker
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability)
    |
    TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx • OncoGuide™ NCC Oncopanel System
    2ms
    GO42286: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors (clinicaltrials.gov)
    P1/2, N=42, Recruiting, Hoffmann-La Roche | Trial completion date: Jun 2033 --> Feb 2032 | Trial primary completion date: Jun 2033 --> Feb 2028
    Trial completion date • Trial primary completion date
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK fusion
    |
    FoundationOne® CDx
    |
    Alecensa (alectinib)
    2ms
    Comparison of actionable alterations in cancers with kinase fusion, mutation, and copy number alteration. (PubMed, PLoS One)
    Cancers with kinase fusions exhibited fewer actionable alterations than those with kinase mutations and CNAs. These findings underscore the importance of detecting kinase alterations and indicate the pivotal role of kinase fusions as strong drivers of cancer development, highlighting their potential as prime targets for molecular therapeutics.
    Clinical • Journal
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx
    2ms
    BLCIO: Beating Lung Cancer in Ohio Protocol in Improving Survival in Patients with Stage IV Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P=N/A, N=3584, Recruiting, Ohio State University Comprehensive Cancer Center | Trial completion date: Dec 2027 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1)
    |
    FoundationOne® CDx
    2ms
    DGKalpha inhibitor BAY 2862789 FiH trial in advanced solid cancers (ChiCTR2400093606)
    P1, N=81, Jilin Cancer Hospital; Jilin Cancer Hospital
    New P1 trial
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • CD4 (CD4 Molecule)
    |
    EGFR mutation • MSI-H/dMMR • BRAF positive
    |
    FoundationOne® CDx • Guardant360® CDx • Ventana MMR RxDx Panel • OncoMate™ MSI
    |
    BAY 2862789
    3ms
    U.S. Food and Drug Administration Approves FoundationOne CDx as a Companion Diagnostic for OJEMDA (tovorafenib) to Treat the Most Common Form of Childhood Brain Tumor in Pediatric Patients (Businesswire)
    "Foundation Medicine, Inc. today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for FoundationOne CDx to be used as a companion diagnostic for Day One Biopharmaceuticals’ OJEMDA, a type II RAF inhibitor, for the treatment of patients six months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. FoundationOne CDx is the first and only companion diagnostic for OJEMDA."
    FDA approval
    |
    BRAF (B-raf proto-oncogene)
    |
    FoundationOne® CDx
    |
    Ojemda (tovorafenib)
    3ms
    ECOG-ACRIN LUNG-MAP SUB-STUDY: Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=116, Active, not recruiting, SWOG Cancer Research Network | Recruiting --> Active, not recruiting
    Enrollment closed • Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • ALK fusion • ROS1 fusion • KRAS G12
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    3ms
    Genomic characterization and molecular predictive biomarkers for chemotherapy in patients with metastatic triple-negative breast cancer treated in a real-world setting. (PubMed, Breast)
    Patients with tumor alterations in HRD-related genes seem to define subgroups that respond favorably to platinum-based chemotherapy. Further research into the genomic landscape of tumors from patients with rapid progression or exceptional response to different treatment strategies can provide insights into mechanisms of resistance and identify predictive biomarkers.
    Journal • Real-world evidence
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRD (Homologous Recombination Deficiency) • RAD21 (RAD21 Cohesin Complex Component)
    |
    HRD
    |
    FoundationOne® CDx
    3ms
    GO42286: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors (clinicaltrials.gov)
    P1/2, N=42, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2030 --> Jun 2033 | Trial primary completion date: Jun 2026 --> Jun 2033
    Trial completion date • Trial primary completion date
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK fusion
    |
    FoundationOne® CDx
    |
    Alecensa (alectinib)
    3ms
    GO42286: A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Alectinib in Pediatric Participants With ALK Fusion-Positive Solid or CNS Tumors (clinicaltrials.gov)
    P1/2, N=42, Recruiting, Hoffmann-La Roche | Trial completion date: Jul 2030 --> Jun 2033 | Trial primary completion date: Jun 2026 --> Jun 2033
    Trial completion date • Trial primary completion date
    |
    ALK (Anaplastic lymphoma kinase)
    |
    ALK fusion
    |
    FoundationOne® CDx
    |
    Alecensa (alectinib)
    3ms
    COPERNIC: A Study of On-treatment ctDNA Changes in Chemo-refractory Colorectal Cancer Patients (clinicaltrials.gov)
    P=N/A; Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Jan 2026 --> Apr 2026
    Trial completion date • Trial primary completion date • Circulating tumor DNA
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx • FoundationOne®Tracker
    4ms
    Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature. (PubMed, Cancers (Basel))
    This subgroup of IO-responsive NS-pts may have better prognosis. Our findings suggest that DDR-based mutational profiling may help identify NS-pts who could benefit from IO therapy.
    Journal • Real-world evidence • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Real-world
    |
    TMB (Tumor Mutational Burden)
    |
    TMB-H • TMB-L • DDR signature score
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    4ms
    The genomic landscape of cutaneous squamous cell carcinoma in Japan. (PubMed, J Dermatol)
    TMB-high (≥10 mut/Mb) was observed in 27% (n = 41) of the patients, with a median age of 75 years for this group. TMB-low (<10 mut/Mb) was observed in 73% (n = 111) of the patients; their median age was 67 years.
    Journal • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TMB-H • TMB-L
    |
    FoundationOne® CDx
    4ms
    Comprehensive genomic profiling of primary bladder mucinous adenocarcinoma, a rare genitourinary cancer: A case report. (PubMed, Urol Case Rep)
    She underwent treatment with paclitaxel-ifosfamide-cisplatin (TIP). After two cycles of TIP therapy, FoundationOne CDx, a comprehensive genomic profiling test, was performed, revealing variants in ATM, SMAD4, BRD4, and NOTCH3. These genomic profiling test results may lead to the development of novel therapeutic agents for primary bladder mucinous adenocarcinoma.
    Journal
    |
    SMAD4 (SMAD family member 4) • NOTCH3 (Notch Receptor 3) • BRD4 (Bromodomain Containing 4)
    |
    FoundationOne® CDx
    |
    cisplatin • paclitaxel • ifosfamide
    4ms
    Berzosertib and Irinotecan in Treating Patients With Progressive, Metastatic, or Unresectable TP53 Mutant Gastric or Gastroesophageal Junction Cancer (clinicaltrials.gov)
    P2; Trial completion date: Jul 2024 --> Dec 2025
    Combination therapy • Trial completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MSI (Microsatellite instability)
    |
    HER-2 positive • TP53 mutation • MSI-H/dMMR
    |
    FoundationOne® CDx
    |
    irinotecan • berzosertib (M6620)
    4ms
    Adrenocortical carcinoma with circulating tumor DNA analysis at post-operative recurrence: a case report with review of literature. (PubMed, Endocr J)
    Post-operatively, adjuvant chemotherapy with mitotane was commenced because of histologically high-grade ACC...At both time-points, CTNNB1 mutations consistent with the primary tumor were observed in ctDNA, with the allelic ratio increasing over time from 8% to 27%. In conclusion, monitoring the ctDNA allelic ratio may be useful for evaluating disease progression in advanced ACC.
    Journal • Review • Circulating tumor DNA
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    CTNNB1 mutation
    |
    FoundationOne® CDx
    |
    Lysodren (mitotane)
    4ms
    LUNG-MAP Sub-Study: Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) (clinicaltrials.gov)
    P2; Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jun 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR T790M • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation
    |
    FoundationOne® CDx
    |
    Retevmo (selpercatinib)
    4ms
    Genomic Analysis of Advanced Phyllodes Tumors Using Next-Generation Sequencing and Their Chemotherapy Response: A Retrospective Study Using the C-CAT Database. (PubMed, Medicina (Kaunas))
    One patient with a high tumor mutational burden (37/Mb) responded to pembrolizumab... Our findings suggest distinct molecular patterns in phyllodes tumors compared to other soft tissue sarcomas, with potential implications for treatment selection. The identification of specific genetic alterations associated with treatment resistance may guide therapeutic decision-making, while the presence of actionable mutations in select cases indicates potential opportunities for targeted therapy approaches.
    Journal • Retrospective data • Tumor mutational burden • PD(L)-1 Biomarker • Next-generation sequencing • Metastases
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSH6 (MutS homolog 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • TMB-H
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    |
    Keytruda (pembrolizumab)
    4ms
    Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database. (PubMed)
    Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.
    Journal • BRCA Biomarker
    |
    FoundationOne® CDx • OncoGuide™ NCC Oncopanel System
    |
    gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium
    4ms
    Analysis of cancer multigene panel testing for osteosarcoma in pediatric and adults using the center for cancer genomics and advanced therapeutics database in Japan. (PubMed)
    "Precision medicine for rare tumors still poses challenges. In this Japanese cohort, 42.2 % of high-grade OSs had potentially actionable alterations per CKDB. Concurrent gene amplifications of KIT, KDR, and PDGFRA at 4q12, and VEGFA and CCND3 at 6p12-21, might offer promising therapeutic options for patients with recurrent/metastatic OS resistant to conventional chemotherapy."
    Journal
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx • MSK-IMPACT • OncoGuide™ NCC Oncopanel System
    5ms
    PTEN alteration as a predictor of second-line efficacy in patients with recurrent IDHwt-glioblastoma (rGBM) (AIOM 2024)
    Nitrosoureas (NS) such as lomustine and fotemustine and antiangiogenic drugs such as regorafenib(Reg) and bevacizumab (Bev) are all treatment options for rGBM. We concluded that pathogenic PTEN alteration may be a predictor of poor efficacy of regorafenib and lomustine in rGBM patients. However, a prospective study with a larger population is needed to better define the role of pTEN in these patient populations.
    Clinical
    |
    PTEN (Phosphatase and tensin homolog) • MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    PTEN mutation • IDH wild-type
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    5ms
    Advanced Intrahepatic Cholangiocarcinoma (iCCA): Investigating Co-Molecular Alterations (AIOM 2024)
    The FGFR and IDH-1 pathways are the primary targets for therapy, with FGFR-2 and IDH-1 inhibitors, such as Pemigatinib and Ivosidenib respectively, already available on the market. This prospective study validates the prevalence of mutations documented in the literature and underscores the significance of NGS in presenting supplementary therapeutic avenues. Moreover, we demonstrated the role of other potential targets co-expressed with FGFR2 or IDH1 which could represent a crucial opportunity for novel combinations or sequences therapies.
    BRCA Biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NTRK (Neurotrophic receptor tyrosine kinase) • CA 19-9 (Cancer antigen 19-9)
    |
    TP53 mutation • KRAS mutation • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • CDKN2A mutation • BAP1 mutation • FGFR2 expression • FGFR2b expression
    |
    FoundationOne® CDx
    |
    Pemazyre (pemigatinib) • Tibsovo (ivosidenib)
    5ms
    A novel machine learning model integrating clinical and molecular data to predict response to second line treatment in recurrent IDHwtglioblastoma (AIOM 2024)
    Background : Nitrosoureas (lomustine/fotemustine) and antiangiogenic drugs (bevacizumab or regorafenib) are second-line treatment options for patients with recurrent IDHwt-glioblastoma (rGBM). The multi-classification ML model developed in this study was able to identify clinical and molecular signatures of recurrent glioblastoma patients responding to specific second-line treatment with bevacizumab or regorafenib or nitrosoureas.
    Clinical • Machine learning
    |
    EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    TP53 mutation • EGFR mutation • PTEN mutation • IDH wild-type • MTAP mutation
    |
    FoundationOne® CDx
    |
    Avastin (bevacizumab) • Stivarga (regorafenib) • lomustine • Muphoran (fotemustine)
    5ms
    Prognostic impact of concomitant genomic alterations in patients affected by FGFR2-positive locally advanced unresectable or metastatic cholangiocarcinoma treated with pemigatinib as second or further line of systemic treatment: molecular analysis of the real-world Italian PEMIREAL and French PEMIBIL cohort studies (AIOM 2024)
    Our results seem to confirm the negative prognostic role in terms of PFS of GA in BAP1 and CDKN2A genes in patients affected by locally advanced or metastatic FGFR2-positive CCA treated with pemigatinib in a real-world setting.
    Clinical • Real-world evidence • Real-world • Metastases
    |
    TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
    |
    FGFR2 fusion • CDKN2A mutation
    |
    FoundationOne® CDx
    |
    Pemazyre (pemigatinib)
    5ms
    Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
    Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
    Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    5ms
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
    |
    FoundationOne® CDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    5ms
    PIK3CA mutations in endometrial cancer: a pre-planned biomarker analysis from the phase II MITO END-3 study of carboplatin and paclitaxel with or without avelumab in advanced or recurrent endometrial cancer (AIOM 2024)
    The frequent alterations of the PI3K pathway in gynecological cancers could emerge as new treatment target. Our data confirm the high frequency of PIK3CA mutations establishing EC as an ideal candidate for testing of PI3K inhibitors regardless of the TCGA classification. Moreover, these data confirm that other targetable mutations are present also in MSS EC group thus suggesting that new target agents should be explored.
    P2 data • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon)
    |
    TP53 mutation • MSI-H/dMMR • PIK3CA mutation • TP53 wild-type • PIK3CA H1047R • PTEN mutation • ARID1A mutation • POLE mutation • PIK3CA E545K • PIK3CA E545 • PIK3CA E542 • PIK3CA H1047L • PIK3CA mutation + PTEN mutation • PIK3CA C420R • PIK3CA E545A • PIK3CA E545G • PIK3CA Q546 • PIK3CA Q546R
    |
    FoundationOne® CDx
    |
    carboplatin • paclitaxel • Bavencio (avelumab)
    5ms
    Liquid biopsy-based comprehensive genomic profiling captures tumor heterogeneity and identifies cancer vulnerabilities in patients with RAS/BRAFV600E wild type metastatic colorectal cancer in the CAPRI 2-GOIM trial (AIOM 2024)
    Materials and The phase II CAPRI 2-GOIM trial investigates the efficacy and safety of biomarkerdriven, cetuximab-based, sequence of three treatment lines in mCRC... Baseline plasma-based comprehensive genomic profiling is feasible with high concordance with tissue-based analysis. Liquid biopsy allows identification of misdiagnosed RAS/BRAF alterations and the ultra-selection of pts, which could benefit from anti-EGFR therapies. Finally, potentially actionable gene alterations were found in half of the pts.
    Clinical • Late-breaking abstract • Liquid biopsy • Metastases • Biopsy
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • RAS (Rat Sarcoma Virus)
    |
    BRAF V600E • KRAS mutation • HER-2 amplification • NRAS mutation • BRAF V600 • PTEN mutation • BRAF wild-type • NF1 mutation • EGFR amplification + ERBB2 amplification
    |
    FoundationOne® CDx
    |
    Erbitux (cetuximab)
    5ms
    Negative hyperselection and mechanisms of acquired resistance to first-line chemotherapy plus anti-EGFR in pMMR RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts): a translational analysis of the TRIPLETE trial (AIOM 2024)
    TRIPLETE is a phase III trial where 435 pts with RAS/BRAF wt – per local assessment – mCRC were randomized to receive first-line FOLFOX/ panitumumab (pan) or mFOLFOXIRI/pan... In contrast to previous data, negative hyperselection both through tissue and plasma analysis failed to demonstrate a prognostic role among pMMR RAS/BRAF wt mCRC pts treated with first-line chemotherapy plus pan. The confounding effect of the associated chemotherapy is a potential explanation for this finding. Tissue and plasma analyses at baseline failed to provide fully concordant results.
    Clinical • Preclinical • Metastases
    |
    BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • BRAF wild-type • RAS mutation • RAS wild-type
    |
    FoundationOne® CDx • Oncomine™ Pan-Cancer Cell-Free Assay • Oncomine Focus Assay
    |
    5-fluorouracil • Vectibix (panitumumab) • leucovorin calcium
    5ms
    First results from the Italian cholangiocarcinoma dataset (ANITA): extended molecular profiling (EMP), access to targeted treatment (TT) and clinical characterization of FGFR2- rearranged and IDH1-mutated advanced biliary tract cancers (BTC) (AIOM 2024)
    Among pts with EMP available, 64.2% had intrahepatic cholangiocarcinoma and 69.8% received CT1 (36.1% cisplatinum-gemcitabine). Despite a broader availability of EMP in advanced BTC in recent years, access to TT remains suboptimal even in referral Institutions. Our results demonstrate TT administration as a pivotal positive prognostic factor in a real-world setting, whilst FGFR2 or IDH1 alterations did not act as prognostic determinants per-se. Therefore, strategies aiming at improving the rate of patients receiving TT are warranted.
    Clinical • Metastases
    |
    FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation • FGFR2 mutation • FGFR2 fusion • IDH1 R132
    |
    FoundationOne® CDx
    |
    cisplatin • gemcitabine