Showing papers by "Fabrice Barlesi published in 2019"
Memorial Sloan Kettering Cancer Center1, Complutense University of Madrid2, Samsung Medical Center3, Hospital Italiano de Buenos Aires4, Aix-Marseille University5, University Hospital of Lausanne6, National and Kapodistrian University of Athens7, Bristol-Myers Squibb8, Emory University9, Princess Alexandra Hospital10, AstraZeneca11
TL;DR: First-line treatment with nivolumab plus ipilimumab resulted in a longer duration of overall survival than did chemotherapy in patients with NSCLC, independent of the PD-L1 expression level.
Abstract: Background In an early-phase study involving patients with advanced non–small-cell lung cancer (NSCLC), the response rate was better with nivolumab plus ipilimumab than with nivolumab mono...
1,588 citations
Paul Sabatier University1, Memorial Sloan Kettering Cancer Center2, university of lille3, University of Paris-Sud4, Aix-Marseille University5, Radboud University Nijmegen6, Stanford University7, Ben-Gurion University of the Negev8, University of Bern9, University of Colorado Boulder10, The Royal Marsden NHS Foundation Trust11, University of California, Irvine12, University Hospital of Basel13, University of Turin14, University of Zurich15, University of Grenoble16, University of Duisburg-Essen17
TL;DR: In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2) and the lack of response in the ALK group was notable.
719 citations
TL;DR: Improved overall survival with ABCP versus BCP was observed in patients with sensitising EGFR mutations, and overall survival in the intention-to-treat population, including EGFR-positive patients and patients with baseline liver metastases.
616 citations
University of Ulsan1, Yale Cancer Center2, Sarah Cannon Research Institute3, New Generation University College4, Memorial Sloan Kettering Cancer Center5, University of Valencia6, Université Paris-Saclay7, Harvard University8, Samsung Medical Center9, Johns Hopkins University10, Aix-Marseille University11, Beth Israel Deaconess Medical Center12, Genentech13, University of Colorado Boulder14
TL;DR: The combination of navoximod and atezolizumab demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer and demonstrated a linear pharmacokinetic profile.
Abstract: Purpose: IDO1 induces immune suppression in T cells through l-tryptophan (Trp) depletion and kynurenine (Kyn) accumulation in the local tumor microenvironment, suppressing effector T cells and hyperactivating regulatory T cells (Treg). Navoximod is an investigational small-molecule inhibitor of IDO1. This phase I study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of navoximod in combination with atezolizumab, a PD-L1 inhibitor, in patients with advanced cancer. Patients and Methods: The study consisted of a 3+3 dose-escalation stage (n = 66) and a tumor-specific expansion stage (n = 92). Navoximod was given orally every 12 hours continuously for 21 consecutive days of each cycle with the exception of cycle 1, where navoximod administration started on day −1 to characterize pharmacokinetics. Atezolizumab was administered by intravenous infusion 1,200 mg every 3 weeks on day 1 of each cycle. Results: Patients (n = 157) received navoximod at 6 dose levels (50–1,000 mg) in combination with atezolizumab. The maximum administered dose was 1,000 mg twice daily; the MTD was not reached. Navoximod demonstrated a linear pharmacokinetic profile, and plasma Kyn generally decreased with increasing doses of navoximod. The most common treatment-related AEs were fatigue (22%), rash (22%), and chromaturia (20%). Activity was observed at all dose levels in various tumor types (melanoma, pancreatic, prostate, ovarian, head and neck squamous cell carcinoma, cervical, neural sheath, non–small cell lung cancer, triple-negative breast cancer, renal cell carcinoma, urothelial bladder cancer): 6 (9%) dose-escalation patients achieved partial response, and 10 (11%) expansion patients achieved partial response or complete response. Conclusions: The combination of navoximod and atezolizumab demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. Although activity was observed, there was no clear evidence of benefit from adding navoximod to atezolizumab.
158 citations
TL;DR: For patients with KRAS-mutant NSCLC (all mutational subtypes), the efficacy of ICI is similar to that for patients with other types of NSCLCs, and this finding is especially true when PD-L1 expression is high (PD-L 1 expression ≥50%).
145 citations
TL;DR: There are signs of late response not sufficient to justify the development of crizotinib in patients with ROS1-translocated tumours, but the continued targeting of c-MET with innovative therapies appears justified.
112 citations
TL;DR: This report presents the largest case series showing longer OS and PFS and better ORR when IRAEs occurred in a population of patients with advanced NSCLC treated with ICIs.
110 citations
Memorial Sloan Kettering Cancer Center1, Harvard University2, Institut Gustave Roussy3, Sarah Cannon Research Institute4, Seoul National University Bundang Hospital5, Samsung Medical Center6, Ohio State University7, University of California, San Francisco8, University of California, San Diego9, University of Pennsylvania10, Cleveland Clinic11, University of North Carolina at Chapel Hill12, Soroka Medical Center13, University Health System14, City of Hope National Medical Center15, Huntsman Cancer Institute16, Tottori University17, University of Chicago18, University of Wisconsin-Madison19, University of California, Irvine20, University of Maryland Medical Center21, Asan Medical Center22, Hebrew University of Jerusalem23, Okayama University24, Kaiser Permanente25, Kanazawa University26, Hokkaido University27, Washington University in St. Louis28, Yale University29, Eli Lilly and Company30, University of Texas MD Anderson Cancer Center31
73 citations
TL;DR: It is suggested that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population.
47 citations
45 citations
TL;DR: Roniciclib combined with chemotherapy demonstrated an unfavorable risk‐benefit profile in patients with extensive‐disease SCLC, and the study was prematurely terminated.
TL;DR: The recent first-line phase 3 trials evaluating PD-(L)1 blockade plus chemotherapy (ChT) and PD-1 plus CTLA-4 CPI for advanced NSCLC are summarized and potential treatment recommendations are provided.
TL;DR: Patients with early-stage NSCLC (stage IA–IIIA) account for ~40% of cases at diagnosis; despite surgery, 5-year survival rates are low and platinum-based adjuvant chemotherapy is recommended.
Abstract: TPS8569Background: Patients with early-stage NSCLC (stage IA–IIIA) account for ~40% of cases at diagnosis; despite surgery, 5-year survival rates are low. Platinum-based adjuvant chemotherapy is th...
TL;DR: Data available on the most frequently used tools to assess ADL and IADL in a geriatric oncology setting and their predictive values on overall survival, toxicity, treatment feasibility or decision and postoperative complications are reviewed.
TL;DR: The rate of METex14 mutations inNSCLC with high MET overexpression was similar to that found in unselected NSCLC and a high frequency of driver alterations in other oncogenes was observed, which does not support the use of MET IHC as a surrogate marker for METex 14 mutations.
TL;DR: Oral vinorelbine is an active and well-tolerated chemotherapy in metastatic NSCLC and is a manageable therapy in frail patients.
Abstract: INTRODUCTION:
Several non-comparative phase II studies have evaluated metronomic oral vinorelbine (MOV) in metastatic non-small cell lung cancer (NSCLC) but the small size of each study limits their conclusions.
PURPOSE:
To perform an individual patient-data metaanalysis of studies evaluating MOV in metastatic NSCLC in order to measure survival and safety of treatment with this regimen.
METHODS:
Studies were selected if (1) administration of oral vinorelbine thrice a week; (2) fixed daily dose comprised between 30 and 50 mg, and; (3) being published before October 4th 2018. Database encompassed 8 variables characterizing disease and demography, 3 informing therapy, and 12 describing survival and toxicity.
RESULTS:
Nine studies encompassing 418 patients fulfilled the selection criteria, 80% of them having frailty characteristics. Median overall survival (OS) was 8.7 months (95%CI: 7.6-9.5). OSrates at 6 months, one year and at two years after starting vinorelbine were 64%, 30.3% and 8.9%, respectively. In the Cox model, Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2, and anemia of any grade were significant determinants of shorter OS. Median progression-free survival(PFS) was 4.2 months (95%CI: 3.9-5). At 6 months and at one-year, PFS rates were 35% and 11.9% respectively. In the Cox model stratified for the variable "study", PS = 2and stage IV were significant determinants of shorter PFS. No toxicity was reported for 40% of patients, and 66 (15.8%) patients experienced a grade 3-4 toxicity. The most frequent toxicity was anemia of any grade (35.8%) that was higher with the 50 mg dosage.
CONCLUSION:
MOV is an active and well-tolerated chemotherapy in metastatic NSCLC and is a manageable therapy in frail patients.
TL;DR: Durable OS outcomes were observed with first-line NIVO+IPI in patients with advanced NSCLC (cohort A) and were comparable to CheckMate 227; although as expected, comorbidities and/or poor performance status impacted outcomes in cohort A1.
TL;DR: There was no significant difference in first-line and second-line progression-free survival between the groups, as well as in the disease control rate, and BRAF mutation was not found to be prognostic of overall survival.
University of Colorado Boulder1, Aix-Marseille University2, University of California, Los Angeles3, Washington University in St. Louis4, Harvard University5, University of Chicago6, Institut Gustave Roussy7, National Cheng Kung University8, University of Texas MD Anderson Cancer Center9, Duke University10, AbbVie11, University of California, Davis12
TL;DR: Telisotuzumab vedotin (ABBV-399; teliso-v [T]) is a c-Met–targeted antibody and MMAE drug conjugate that was shown in late-line c- Met+ non-small cell lung cancer (NSCLC) and showed activity inhibition in animals treated with this drug.
Abstract: 3011Background: Telisotuzumab vedotin (ABBV-399; teliso-v [T]) is a c-Met–targeted antibody and MMAE drug conjugate. Activity of T was shown in late-line c-Met+ non-small cell lung cancer (NSCLC) i...
Aix-Marseille University1, Memorial Sloan Kettering Cancer Center2, University of Milan3, Yonsei University4, Samsung Medical Center5, University of Manchester6, National Taiwan University7, Gdańsk Medical University8, Sarah Cannon Research Institute9, University of Baltimore10, University of Bonn11, Genentech12, University of Colorado Boulder13
TL;DR: Entrectinib is highly active in patients with ROS1 fusion-positive NSCLC, including those with CNS disease, and well tolerated and has a manageable safety profile.
TL;DR: The results of the present study demonstrate that nivolumab affords clinical efficacy and manageable tolerability in patients with non-small cell lung cancers.
Abstract: Nivolumab, a fully human immunoglobulin monoclonal antibody inhibiting the programmed cell death protein-1 receptor, demonstrated robust efficacy and a manageable safety profile across multiple tumor types in clinical trials. The aim of the present study was to investigate the efficacy and safety of nivolumab for pretreated patients with non-small cell lung cancers in clinical practice. In this observational monocentric retrospective study, 98 patients were enrolled between February 2015 and February 2016. The global median overall survival was 6.34 months (95% confidence interval (CI) : 4.11-10.88) and the global median progression free survival was 1.84 months (95% CI: 1.68-2.73). In the univariate analysis, clinical performance status score was the only factor significantly correlated with overall survival. The safety profile of nivolumab is consistent with that described in prior studies, with only 7% undesirable effects requiring the discontinuation of treatment. The results of the present study demonstrate that nivolumab affords clinical efficacy and manageable tolerability in patients with non-small cell lung cancers.
TL;DR: VeriStrat showed a prognostic role within Eastern Cooperative Oncology Group (ECOG) performance score (PS) categories and regardless of treatment arm and EGFR status, suggesting that Veri Strat could be used to identify EGFR mutation-positive patients who will have a poor response to EGFR tyrosine kinase inhibitors.
Abstract: BACKGROUND The VeriStrat test provides accurate predictions of outcomes in all lines of therapy for patients with non-small cell lung cancer (NSCLC). We investigated the predictive and prognostic role of VeriStrat in patients enrolled on the MARQUEE phase III trial of tivantinib plus erlotinib (T+E) versus placebo plus erlotinib (P+E) in previously treated patients with advanced NSCLC. METHODS Pretreatment plasma samples were available for 996 patients and were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to generate VeriStrat labels (good, VS-G, or poor, VS-P). RESULTS Overall, no significant benefit in overall survival (OS) and progression-free survival (PFS) were observed for the addition of tivantinib to erlotinib. Regardless of treatment arm, patients who were classified as VS-G had significantly longer PFS (3.8 mo for T+E arm, 2.0 mo for P+E arm) and OS (11.6 mo for T+E, 10.2 mo for P+E arm) than patients classified as VS-P (PFS: 1.9 mo for both arms, hazard ratio [HR], 0.584; 95% confidence interval [CI], 0.468-0.733; p < .0001 for T+E, HR, 0.686; 95% CI, 0.546-0.870; p = .0015 for P+E; OS: 4.0 mo for both arms, HR, 0.333; 95% CI, 0.264-0.422; p < .0001 for T+E; HR, 0.449; 95% CI, 0.353-0.576; p < .0001 for P+E). The VS-G population had higher OS than the VS-P population within Eastern Cooperative Oncology Group (ECOG) performance score (PS) categories. VS-G patients on the T+E arm had longer PFS, but not OS, than VS-G patients on the P+E arm (p = .0108). Among EGFR mutation-positive patients, those with VS-G status had a median OS more than twice that of any other group (OS: 31.6 mo for T+E and 22.8 mo for P+E), whereas VS-P patients had similar survival rates as VS-G, EGFR-wild type patients (OS: 13.7 mo for T+E and 6.5 mo for P+E). CONCLUSION In these analyses, VeriStrat showed a prognostic role within EGOC PS categories and regardless of treatment arm and EGFR status, suggesting that VeriStrat could be used to identify EGFR mutation-positive patients who will have a poor response to EGFR tyrosine kinase inhibitors. IMPLICATIONS FOR PRACTICE This study suggests that VeriStrat testing could enhance the prognostic role of performance status and smoking status and replicates findings from other trials that showed that the VeriStrat test identifies EGFR mutation-positive patients likely to have a poor response to EGFR tyrosine kinase inhibitors (TKIs). Although these findings should be confirmed in other populations, VeriStrat use could be considered in EGFR mutation-positive patients as an additional prognostic tool, and these results suggest that EGFR mutation-positive patients with VeriStrat "poor" classification could benefit from other therapeutic agents given in conjunction with TKI monotherapy.
University of California, Los Angeles1, Aix-Marseille University2, Yonsei University3, University of São Paulo4, Shanghai Chest Hospital5, University of Texas MD Anderson Cancer Center6, Peter MacCallum Cancer Centre7, Sarah Cannon Research Institute8, University Hospital Heidelberg9, National Taiwan University10, Harvard University11
TL;DR: This data indicates that the cytokine interleukin-1β can promote the infiltration of immunosuppressive cells into the tumor micro...
Abstract: TPS9124Background: Inflammatory pathways can be pro-tumorigenic or anti-tumorigenic. The cytokine interleukin-1β (IL-1β) can promote the infiltration of immunosuppressive cells into the tumor micro...
TL;DR: Ceritinib demonstrated a clinically efficacy and a meaningful safety profile similar to ALK+ NSCLC pts with LM similar to crizotinib, and overall response rate, disease control rate, and progression-free survival were demonstrated.
TL;DR: This phase II, open-label, single-arm study is designed to assess the efficacy and safety of afatinib in combination with pembrolizumab in patients with stage IIIB/IV lung SCC that has progressed during/after first-line platinum-based chemotherapy.
TL;DR: A 2-part, single-arm, multicenter, phase 1b trial to test the safety and efficacy of necitumumab plus abemaciclib in patients with advanced NSCLC who had received ≤2 lines of chemotherapy, including a platinum-based one found the safety profile was consistent with the individual study drugs.