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  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 1034-1034
    Abstract: Introduction Liquid biopsy (LB) is increasingly used in non-small cell lung cancer (NSCLC) for molecular diagnosis or resistance detection. Due to its non-invasive nature, it is often preferred over tissue biopsies, especially when sequential biopsies are warranted. Here, we report the clinical utility of liquid biopsy in patients with advanced NSCLC and ALK, ROS1 or RET fusions and its relevance to detect resistance after targeted therapy. Methods Between December 2020 and June 2022, 597 patients with advanced lung cancer had at least one liquid biopsy assessed by Foundation One CDx Liquid (panel of 324 genes) in a single institution. Plasma collection was performed in treatment-naïve patients and/or at time of progression. Clinical and molecular data were collected from patients with known fusions (ALK, ROS1, RET). LB were defined as “positive” if the fusion or resistance mutations were identified and “negative” in the absence of circulating-tumor DNA. The clinical utility of LB was evaluated as the proportion of positive results. The clinical relevance for resistance detection was defined as the proportion of LB that identified a putative resistance mechanism after targeted therapy. Results A total of 68 patients (29 ALK+, 22 RET+ and 17 ROS1+) with 83 LB were included. Patients were females in 50% of cases, had no smoking history in 58% of cases and had adenocarcinoma in 91% of cases. LB was positive in 55/83 (66%) cases overall, in 14/15 (93%) treatment-naïve patients and in 39/66 (59%) pre-treated patients. Factors significantly associated with a negative LB were limited disease progression (brain- or thoracic-only, p & lt;0.001) and ongoing treatment at time of LB collection (p & lt;0.05). Out of 47 LB performed at progression after targeted therapies, 7 (15%) found on-target resistance, 10 (21%) by-pass resistance, 10 (21%) no explainable resistance and 20 (43%) were negative. By-pass alterations included KRAS p.G12C/A mutations (N=2, ALK+), PIK3CA p.E545K/Q (N=3, ALK+), PTEN splice-site mutation (N=1, RET+), MYC amplifications (N=3, ALK+/RET+) and MET amplification (N=1, ROS1+). Conclusion LB was able to detect resistance mechanisms in one third of NSCLC patients with ALK, RET or ROS1 fusions. However, LB frequently failed to detect circulating-tumor DNA especially in patients with limited disease progression or with ongoing treatment at time of sample collection. Citation Format: Mihaela Aldea, Arianna Marinello, Marco Tagliamento, Filippo Dall'Olio, Damien Vasseur, Arnaud Bayle, Anas Gazzah, Miruna Grecea, Claudio Nicotra, Ludovic Lacroix, Santiago Ponce, Luc Friboulet, Fabrice Barlesi, Fabrice Andre, David Planchard, Etienne Rouleau, Antoine Italiano, Benjamin Besse. Clinical utility of liquid biopsy for molecular characterization and resistance detection in patients with advanced NSCLC and ALK, ROS1 or RET fusions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1034.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 18_Supplement ( 2020-09-15), p. PO-030-PO-030
    Abstract: Background: The SARS-CoV-2 outbreak in Paris’s region significantly affected Gustave Roussy Cancer Center. Previous analyses showed that mortality rate increases with age in the general population. Here, we report the Gustave Roussy experience on older patients (OP) with cancer during the SARS-CoV-2 outbreak. Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March 12th. Screening indications have been adapted over the time. All the COVID19 pts positively tested and managed at Gustave Roussy between March 14th (1st positive case) and April 15th have been included in a REDCap database. Pts and underlying oncologic and COVID19 diseases characteristics have been collected. Cancer and COVID-19 managements and outcomes have been assessed. The primary endpoint of this analysis was the clinical deterioration, defined as the need for O2 supplementation of 6l/min, or death of any cause. Results: Among the first 137 cancer pts diagnosed with SARS-CoV-2, 36 patients were aged 70 years (26%). Most of them were female (61%) with a median age of 75.5 years old. Most frequent underlying cancers were solid tumors (92%) including GI (19%), lung (17%), GYN (14%), and head and neck (14%). Most OP (36%) were ECOG performance status 2 versus 24% in younger patients (YP). The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 97% and 3% of the cases, respectively, in OP and in 92% and 8% in YP. Most OP experienced symptoms prior to testing (92%) compared to YP (80%). Symptoms differed according to age with more cough with sputum production in OP (14% versus 5%), dyspnea (39% versus 31%), diarrhea (17% versus 9%), shivers (8% versus 0%), sore throat (8% versus 4%), and no anosmia or agueusia. The majority of OP were hospitalized (81%) compared to 72% of YP and treated with HCQ/AZI (15; 52%) with inclusion in the ONCOVID trial (EudraCT: 2020-01250-21) compared to 25 (35%) YP. They did not receive any IL-6 inhibitor. Only one OP was admitted in the ICU (3%). Clinical deterioration occurred in 10 OP (29%). There was no impact of age on clinical worsening (HR=1.157; 95%CI 0.55-2.42; p=0.7). However, age was associated with worse overall survival (OS) (HR=2.45 95%CI 1.02-5.92 ; p=0.0463). Results will be updated at the meeting. Conclusions: OP with cancer had a different disease presentation, same rate of clinical worsening, but worse OS in SARS-CoV-2 infection. Citation Format: Mathilde Hauchecorne, Capucine Baldini, Stéphanie Foulon, Arnaud Bayle, Bertrand Gachot, Fanny Pommeret, Helene Vincent, Tina Lamy, Celine Nagera, Christophe Willekens, Franck Griscelli, Florence Netzer, Corinne Balleyguier, Samy Ammari, Fabrice André, Florian Scotte, Benjamin Besse, Jean-Charles Soria, Fabrice Barlési, Laurence Albigès. Outcome of older cancer patients infected with Covid19 at Gustave Roussy Cancer Center [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-030.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 3
    In: JCO Precision Oncology, American Society of Clinical Oncology (ASCO), , No. 7 ( 2023-03)
    Abstract: High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell–free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors. MATERIALS AND METHODS Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525 ) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in JAK2, MPL, or MYD88, irrespective of the variant allele frequency (VAF), or in DNMT3A, TET2, ASXL1, IDH1, IDH2, SF3B1, or U2AF1 with VAF ≥ 10%, while also considering patient cancer-related prognosis. TP53 mutations were discussed case-by-case. RESULTS Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation: DNMT3A (n = 32), JAK2 (n = 28), TET2 (n = 19), ASXL1 (n = 18), SF3B1 (n = 5), IDH1 (n = 4), IDH2 (n = 3), MPL (n = 3), and U2AF1 (n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology. CONCLUSION The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.
    Type of Medium: Online Resource
    ISSN: 2473-4284
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), ( 2023-07-19), p. OF1-OF14
    Abstract: The androgen receptor axis inhibitors (ARPI; e.g., enzalutamide, abiraterone acetate) are administered in daily practice for men with metastatic castration-resistant prostate cancer (mCRPC). However, not all patients respond, and mechanisms of both primary and acquired resistance remain largely unknown. Experimental Design: In the prospective trial MATCH-R (NCT02517892), 59 patients with mCRPC underwent whole-exome sequencing (WES) and/or RNA sequencing (RNA-seq) of samples collected before starting ARPI. Also, 18 patients with mCRPC underwent biopsy at time of resistance. The objectives were to identify genomic alterations associated with resistance to ARPIs as well as to describe clonal evolution. Associations of genomic and transcriptomic alterations with primary resistance were determined using Wilcoxon and Fisher exact tests. Results: WES analysis indicated that no single-gene genomic alterations were strongly associated with primary resistance. RNA-seq analysis showed that androgen receptor (AR) gene alterations and expression levels were similar between responders and nonresponders. RNA-based pathway analysis found that patients with primary resistance had a higher Hedgehog pathway score, a lower AR pathway score and a lower NOTCH pathway score than patients with a response. Subclonal evolution and acquisition of new alterations in AR-related genes or neuroendocrine differentiation are associated with acquired resistance. ARPIs do not induce significant changes in the tumor transcriptome of most patients; however, programs associated with cell proliferation are enriched in resistant samples. Conclusions: Low AR activity, activation of stemness programs, and Hedgehog pathway were associated with primary ARPIs’ resistance, whereas most acquired resistance was associated with subclonal evolution, AR-related events, and neuroendocrine differentiation.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 3016-3016
    Abstract: 3016 Background: Despite the effectiveness of the various targeted therapies currently approved in solid tumors, acquired resistance remains a persistent problem that limits the ultimate effectiveness of these treatments. Polyclonal resistance to targeted therapy has been described in multiple solid tumors through high throughput analysis of multiple tumor tissue samples from a single patient. However, biopsies at the time of acquired resistance to targeted agents may not always be feasible and may not capture the genetic heterogeneity that could exist within a patient. We used here sequencing of circulating tumor DNA (ctDNA) to characterize the landscape of secondary resistance mechanisms in a large cohort of patients with solid tumors. Methods: This study enrolled patients with advanced cancer from two institutional molecular profiling program STING (NCT04932525, sponsor: Gustave Roussy) or BIP (NCT02534649sponsor: Institut Bergonié). Genomic analysis was performed for each patient by using the Foundation One Liquid CDx Assay (324 genes, tumor mutational burden [TMB], microsatellite instability status). Results: 3435 patients with metastatic disease entered the study. Among them 992 patients (29%) received a targeted therapy matched to a specific molecular alteration before ctDNA. The main tumor types were: prostate cancer (349, 35%), luminal breast cancer (236, 24%), oncogene-addicted non-small cell lung cancer (129, 13%), KRAS-wild type colorectal cancer (126, 13 %). The most frequent class of targeted agents were androgen receptor pathway inhibitor (n = 350, 35%), aromatase inhibitor (236, 24%), anti- EGFR monoclonal antibodies (166, 17%), anti- EGFR tyrosine kinase inhibitors (83, 8%). ctDNA sequencing revealed DNA aberrations involved in secondary resistance in 308 patients (31%). The most frequent aberrations were AR mutations/amplifications, ESR1 point mutations, KRAS point mutations, EGFR point mutations. Among patients with resistance mutation, polyclonal aberrations were identified in 123 patients (40%). The median number of polyclonal aberrations per patient was 2 (range: 2-16). Polyclonal aberrations involved at least 2 different genes in 32 patients (10%). Preliminary results suggest that patients with polyclonal aberrations had worse outcome in comparison with patients with one or no detected aberration and final data will be presented at the time of the congress. Conclusions: We report here the first comprehensive landscape of genomic aberrations in ctDNA involved in resistance to targeted therapies in cancer patients. Polyclonal secondary genomic aberrations represent a frequent clinical resistance mechanism that may explain the poor rate of sustained complete remission observed with targeted therapies and must guide the development of future combinatorial strategies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 6
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 358-358
    Abstract: Background: The androgen receptor axis inhibitors (ARi) (e.g, enzalutamide, abiraterone acetate) are administered in daily practice for men with metastatic castration-resistant prostate cancer (mCRPC). However, not all patients respond, and mechanisms of both primary and acquired resistance remain largely unknown. Methods: In a prospective trial MATCH-R (NCT02517892), 55 mCRPC patients underwent whole exome sequencing (WES) (n=45) and RNA-sequencing (RNA-seq) (n=52) of metastatic biopsies before starting ARi. Also, 16 mCRPC patients underwent biopsy at time of resistance (WES=14, RNA-seq = 14). The objectives were to identify genomic alterations associated with resistance to ARi as well as to describe clonal evolution. Primary resistance was determined at 4 months of treatment using composite criteria for progression that included serum prostate specific antigen measurements, bone scan, CT imaging and symptom assessments. Acquired resistance was defined by occurrence of progressive disease after initial response or stable disease. Associations of genomic and transcriptomic alterations with primary resistance were determined using Wilcoxon and Fisher's exact tests. Results: At 4 months, 22/55 patients in the cohort had disease progression (primary resistance). No genomic alterations from WES analysis were significantly associated with primary resistance. Analysis of sequential biopsies suggests that mCRPC follows mainly a parallel evolution model and involve DNA-repair related mutational processes. At time of acquired resistance to ARi, most tumors acquired new drivers affecting AR pathway (e.g, AR, NCOR1/2) or lineage switching (e.g, RB1, PTEN, TP53). Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis to identify pathways whose activity state correlated with resistance. AR gene alterations and AR expression were similar between responding and non-responding patients. Transcriptional analysis demonstrated that multiple specific gene sets — including those linked to low AR transcriptional activity, stemness program, RB loss and homologous repair deficiency — were activated in both primary and acquired resistance. Conclusion: Resistance to AR axis inhibitors results from multiple transcriptional programs already activated in pre-treatment samples. Clonal evolution analysis along with RNA-seq data indicate the role of genomic instability and lineage switching in driving acquired resistance Citation Format: Naoual Menssouri, Loic Poiraudeau, Carole Helissey, Ludovic Bigot, Jonathan Sabio, Tony Ibrahim, Claudio Nicotra, Maud Ngocamus, Lambros Tselikas, Thierry De Baere, Etienne Rouleau, Ludovic Lacroix, Anne Chaucherau, Luc Friboulet, Ronan Flippot, Giulia Baciarello, Laurence Albiges, Emeline Colomba, Pernelle Lavaud, Stefan Michiels, Aline Maillard, Antoine Italiano, Fabrice Barlesi, Jean-Charles Soria, Jean-Yves Scoazec, christophe Massard, Benjamin Besse, Fabrice André, Karim Fizazi, Daniel Gautheret, Yohann Loriot. A prospective study of prostate cancer metastases identifies an androgen receptor activity-low, stemness program associated with resistance to androgen receptor axis inhibitors and unveils mechanisms of clonal evolution [abstract] . In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 358.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. CT403-CT403
    Abstract: Background: The SARS-CoV-2 outbreak in Paris’ region significantly affected Gustave Roussy cancer center. Here, we report the Gustave Roussy experience during the SARS-CoV-2 outbreak. This outbreak has led to a rapid reorganization of cancer patients’ (pts) management, with two concurrent objectives. First, protect cancer pts, who may experience more severe form of the disease, from being infected by the SARS-CoV-2. Second, protect cancer pts from losing the chance to receive optimal, if not standard, cancer care. Methods: Cancer pts with suspected SARS-CoV-2 infection were admitted at Gustave Roussy starting March, 12th. Screening indications have been adapted over the time. All the COVID19 pts positively tested and managed at Gustave Roussy between March 14th (1st positive case) and April 15th have been included in a redcap database. Pts and underlying oncological and COVID19 diseases characteristics have been collected. Cancer and COVID-19 managements, and outcomes have been assessed. The primary endpoint of this analysis was the clinical deterioration, defined as the need for O2 supplementation of 6l/min or more, or death of any cause. Results: Overall, 7,251 cancer pts were managed at Gustave Roussy during this period of time, with 3616 being hospitalized. Based on our testing strategy, 1302 pts have been tested with 12% of them found positive for SARS-CoV-2. Among the first 137 cancer pts diagnosed with SARS-CoV-2, most cases were female (58%) with a median age of 61 years, including 36 pts (26%) ≥ 70 years. Most frequent underlying cancers were solid tumors (115) including breast (23), GI (18), head and neck (17), GU (17), GYN (17) malignancies or hemopathies (22). At time of COVID diagnosis, 79 pts (58%) had metastatic/active cancer and 56 pts (41%) were considered in remission/treated with curative intent. The diagnosis of SARS-CoV-2 infection was made by RT-PCR or thoracic CT scan alone in 93.4% and 6.6% of the cases, respectively. The majority of the pts was hospitalized (75%) and treated with HCQ/AZI (40; 30%) with inclusion in the ONCOVID trial (EudraCT: 2020-01250-21), IL-6 inhibitor (10), antiviral (6) or steroids (13). Fifteen pts were admitted in ICU (11%). Clinical deterioration occurred in 34 pts (24.8%) and was associated with hematological underlying disease, CRP at diagnosis of COVID19 & gt;50 and the use of cytotoxic chemotherapy within & lt;3mo. At data cut-off (April, 20th 2020), 95 (69.3%), 20 (14.6%), and 22 (16.1%) pts were discharged, had died, or were still hospitalized, respectively. All the deaths were considered related to the SARS-CoV-2 infection. Conclusions: Globally, the rate of the SARS-CoV-2 infection in our cancer patients’ population does not seem to be higher compared to the global population. We have not found evidence that COVID19 is more lethal or aggressive in cancer patients that underwent usual SARS-Cov-2 treatment. We believe that adequate testing and protective measures, along with the low rate of SARS-cov-2-treatment-related adverse events (5.5%), justify an optimal management of the cancer patients’ underlying tumor. Citation Format: Fabrice Barlesi, Stéphanie Foulon, Arnauld Bayle, Bertrand Gachot, Fanny Pommeret, Christophe Willekens, Annabelle Stoclin, Mansouria Merad, Franck GriscelliI, Jean-Baptise Micol, Roger Sun, Thomas Nihouarn, Corinne Balleygier, Fabrice André, Florian Scotte, Benjamin Besse, Jean-Charles Soria, Laurence Albiges. Outcome of cancer patients infected with COVID-19, including toxicity of cancer treatments [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT403.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 3414-3414
    Abstract: Background: Genomic profiling with tissue sequencing is still considered as the gold standard despite several limitations including screening failures due to limited tissue availability, and inability to capture intratumor spatial and temporal heterogeneity, which may impair accurate treatment selection. Several studies have demonstrated the potential of circulating tumor DNA (ctDNA) to detect genomic alterations at high accuracy compared with tissue analysis. However, no studies have comprehensively evaluated differences between tissue and ctDNA by using a large panel in the same cohort. Methods: Genomic analysis was performed for each patient by using the Foundation One Liquid CDx Assay and the Foundation One CDx Assay (324 genes, tumor mutational burden [TMB], microsatellite instability). Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB). Actionable targets were defined by the MTB according to the existing level of evidence (ESCAT tiers) and molecular-based treatment suggestions were proposed where possible. Results: Between Dec 2020 and Nov 2021, 1021 patients (median age: 62 years) with advanced cancer underwent both tissue and ctDNA NGS. Five most frequent tumor types were colorectal (N=137,13%), NSCLC (N=130,13%), breast (N=120, 12%), prostate (N=82, 8%) and pancreas (N=65, 6%). Median time elapsed between request and assay results was 12 days for ctDNA and 46 days for tissue. Testing failure was 15% for tissue and 3.9% for ctDNA. Overall, 824 (81%) patients had evaluable results for both tissue and liquid. Total number of cancer-related alterations and variants of unknown significance were 4704 and 11673 vs 4645 and 7481 for ctDNA and tissue, respectively. Proportion of patients with a higher number of cancer alterations identified in ctDNA compared with tissue increased in parallel with the time elapsed between the tissue and ctDNA sampling (45% vs 33% for a delay & gt; 26 months or & lt; 8 months). MSI and TMB status were concordant for 71% and 64% of patients, respectively. MSI status was evaluable for 97% of patients through ctDNA vs 90% through tissue. Number of actionable alterations was similar in 346 (42%) of cases, whereas it was higher in tissue for 289 (35%) and in liquid for 189 (23%) patients. ctDNA profiling allowed the identification of an ESCAT I/II or III or IV alteration not present in tissue for 74 (9%), 113 (14%) and 52 (6%) patients, respectively. Overall, MTB recommended a matched therapy for 430 patients (52%). Such a recommendation would not have been made without the results of ctDNA for 120 patients (15%). Conclusion: This systematic comparison of ctDNA vs tissue sequencing demonstrates the capacity of ctDNA for capturing clinically relevant alterations to guide therapy in cancer patients with high accuracy and rapid turnover results. Citation Format: Arnaud Bayle, Florent Peyraud, Laila Belcaid, Maxime Brunet, Miha Aldea, Rebecca Clodion, Paul Dubos, Damien Vasseur, Claudio Nicottra, Santiago Ponce, Isabelle Soubeyran, Emmanuel Khalifa, Yohann Loriot, Benjamin Besse, Ludovic Lacroix, Etienne Rouleau, Geoffrey Oxnard, Fabrice Barlesi, Fabrice Andre, Antoine Italiano. Systematic comparison of ctDNA vs tissue sequencing with a large panel to guide therapy in patients with advanced cancer: A study from the French National Center for Precision Medicine (PRISM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3414.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 9
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 3413-3413
    Abstract: Background: Circulating tumor DNA (ctDNA) sequencing is a promising approach for testing gene alterations and tailoring therapy in cancer patients given, its limited invasiveness, high sensitivity and potential to comprehensively represent tumor heterogeneity. Here, we report the results from a single-center study conducted at Gustave Roussy (Villejuif, France) where we investigated the impact of comprehensive molecular profiling of ctDNA in patients with advanced solid tumors. Methods: Genomic analysis was performed using the Foundation One Liquid CDx Assay (324 genes, tumor mutational burden [TMB], microsatellite instability status). Each individual genomic report was reviewed and discussed weekly by a multidisciplinary tumor board (MTB) dedicated to precision medicine, attended by experts in clinical oncology, molecular biology, and clinical genetics. Actionable targets were defined by the MTB according to the existing level of evidence (classified by ESCAT tier), and molecular-based treatment suggestions were proposed where possible. Results: Between December 2020 and November 2021, 1772 patients with metastatic solid tumors underwent molecular profiling. Median time to assay results was 12 days. Results were contributive for 1658 patients (94%). At least one actionable target was detected in 1059 patients (64%) with a total of 1825 theragnostic alterations including : high blood TMB ( & gt; 16 mutations/Mb) (N= 243, 13%), alteration of the DNA damage repair response pathway (N=336, 18%), PIK3CA mutations (N=150, 8%), FGFR alterations (N= 67, 4%), MET activations (N=13, 0.7%), ERBB family pathway alterations (N=127, 7%) and PTEN mutations (N=95, 5%). Overall, the MTB recommended a matched therapy for 597 patients (56%) with a total of 819 therapeutic orientations: clinical trials (N= 639, 78%), off label/compassionate use (N=81, 10%), drug with a market authorization (N=51, 6%) and drug within an early access program (N=48, 6%). MTB did not recommend treatment for 462 patients (44%) with targetable molecular alterations for the following reasons: no clinical trial (N=421, 65%), matched treatment was already received (N=169, 26%), worsening of performance status (N= 49, 8%). Conclusions: This large-scale study demonstrates that liquid biopsy with a large NGS ctDNA panel is an efficient approach to match patients to genomically directed clinical trials/targeted therapies. Outcomes of patients treated with matched therapy will be presented at the meeting. Citation Format: Arnaud Bayle, Laila Belcaid, Miha Aldea, Florent Peyraud, Patricia Martin Romano, Félix Blanc-Durand, Rebecca Clodion, Santiago Ponce, Claudio Nicotra, Antoine Hollebecque, Yohann Loriot, Benjamin Besse, Damien Vasseur, Ludovic Lacroix, Etienne Rouleau, Jean-Charles Soria, Fabrice Barlesi, Geoffrey R. Oxnard, Fabrice Andre, Antoine Italiano. Clinical utility of circulating tumor DNA sequencing with a large panel: The experience of Gustave Roussy/National Center for Precision Medicine (PRISM) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3413.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 10
    In: Nature Cancer, Springer Science and Business Media LLC, Vol. 1, No. 10 ( 2020-09-22), p. 965-975
    Type of Medium: Online Resource
    ISSN: 2662-1347
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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