4 results on '"Ashara Y"'
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2. Consolidation Osimertinib Versus Durvalumab Versus Observation After Concurrent Chemoradiation in Unresectable EGFR-Mutant NSCLC: A Multicenter Retrospective Cohort Study.
- Author
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Nassar AH, Kim SY, Aredo JV, Feng J, Shepherd F, Xu C, Kaldas D, Gray JE, Dilling TJ, Neal JW, Wakelee HA, Liu Y, Lin SH, Abuali T, Amini A, Nie Y, Patil T, Lobachov A, Bar J, Fitzgerald B, Fujiwara Y, Marron TU, Thummalapalli R, Yu H, Owen DH, Sharp J, Farid S, Rocha P, Arriola E, D'Aiello A, Cheng H, Whitaker R, Parikh K, Ashara Y, Chen L, Sankar K, Harris JP, Nagasaka M, Ayanambakkam A, Velazquez AI, Ragavan M, Lin JJ, Piotrowska Z, Wilgucki M, Reuss J, Luders H, Grohe C, Baena Espinar J, Feiner E, Punekar SR, Gupta S, Leal T, Kwiatkowski DJ, Mak RH, Adib E, Naqash AR, and Goldberg SB
- Subjects
- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Mutation, Consolidation Chemotherapy methods, Indoles, Pyrimidines, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung therapy, Lung Neoplasms pathology, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Lung Neoplasms therapy, Acrylamides therapeutic use, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal pharmacology, Chemoradiotherapy methods, ErbB Receptors genetics, ErbB Receptors antagonists & inhibitors, Aniline Compounds therapeutic use
- Abstract
Introduction: Durvalumab improves survival when used as consolidation therapy after chemoradiation (CRT) in patients with stage III NSCLC. The optimal consolidation therapy for patients with EGFR-mutant (EGFRmut) stage III NSCLC remains unknown., Methods: In this multi-institutional, international retrospective analysis across 24 institutions, we evaluated outcomes in patients with stage III EGFRmut NSCLC treated with concurrent CRT followed by consolidation therapy with osimertinib, durvalumab, or observation between 2015 and 2022. Kaplan-Meier method was used to estimate real-world progression-free survival (rwPFS, primary end point) and overall survival (secondary end point). Treatment-related adverse events (trAEs) during consolidation treatment were defined using Common Terminology Criteria for Adverse Events version 5.0. Multivariable Cox regression analysis was used., Results: Of 136 patients with stage III EGFRmut NSCLC treated with definitive concurrent CRT, 56 received consolidation durvalumab, 33 received consolidation osimertinib, and 47 was on observation alone. Baseline characteristics were similar across the three cohorts. With a median follow-up of 46 months for the entire cohort, the median duration of treatment was not reached (NR) for osimertinib (interquartile range: NR-NR) and was 5.5 (interquartile range: 2.4-10.8) months with durvalumab. After adjusting for nodal status, stage III A/B/C, and age, patients treated with consolidation osimertinib had significantly longer 24-month rwPFS compared to those treated with durvalumab or in the observation cohorts (osimertinib: 86%, durvalumab: 30%, observation: 27%, p < 0.001 for both comparisons). There was no difference in rwPFS between the durvalumab and the observation cohorts. No significant difference in overall survival across the three cohorts was detected, likely due to the limited follow-up. Any-grade trAE occurred in 52% (2 [6.1%] grade ≥3) and 48% (10 [18%] grade ≥3) of patients treated with osimertinib and durvalumab, respectively. Of 45 patients who progressed on consolidation durvalumab, 37 (82%) subsequently received EGFR tyrosine kinase inhibitors. Of these, 14 (38%) patients developed trAEs including five patients with pneumonitis (14%; 2 [5.4%] grade ≥3) and five patients with diarrhea (14%; 1 [2.7%] grade ≥3)., Conclusions: This study suggests that among patients with stage III unresectable NSCLC with a sensitizing EGFR mutation, consolidation osimertinib was associated with a significantly longer rwPFS compared to durvalumab or observation. No unanticipated safety signals were observed with consolidation osimertinib., Competing Interests: Disclosure Dr. Nassar receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology and consulting fees from Guidepoint Global. Dr. Kim is on the advisory board for Amgen. Dr. Shepherd reports having stock and other ownership interests from Eli Lilly and AstraZeneca; receiving honoraria from AstraZeneca, Merck Serono, Takeda, and Daiichi Sankyo; having consulting/advisory role at AstraZeneca and Merck Serono; and receiving research funding from Eli Lilly (inst), Pfizer (inst), Bristol-Myers Squibb (inst), AstraZeneca/MedImmune (inst), and Roche Canada (inst). Dr. Gray reports receiving grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co., Inc., Novartis, and Pfizer; receiving consulting fees from AbbVie, AstraZeneca, Blueprint Medicines, EMD Serono, Gilead Sciences, Inc., Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc., Merck & Co., Inc., Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda Pharmaceuticals, and Triptych Health Partners; and having leadership role as SWOG Lung Committee Chair, IASLC Board of Director member, and ASCO Education Committee Ex-Chair. Dr. Dilling reports receiving consulting fees from AstraZeneca and support for travel from NCCN. Dr. Neal reports receiving grants from Genentech/Roche, Merck, Novartis, Boehringer Ingelheim, Exelixis, Nektar Therapeutics, Takeda Pharmaceuticals, Adaptimmune, GlaxoSmithKline, Janssen, AbbVie, and Novocure; receiving consulting fees from AstraZeneca, Genentech/Roche, Exelixis, Takeda Pharmaceuticals, Eli Lilly and Company, Amgen, Iovance Biotherapeutics, Blueprint Pharmaceuticals, Regeneron Pharmaceuticals, Natera, Sanofi/Regeneron, D2G Oncology, Surface Oncology, Turning Point Therapeutics, Mirati Therapeutics, Gilead Sciences, AbbVie, Summit Therapeutics, Novartis, Novocure, Janssen Oncology, and AnHeart Therapeutics; and receiving honorarium from CME Matters, Clinical Care Options CME, Research to Practice CME, Medscape CME, Biomedical Learning Institute CME, MLI Peerview CME, Prime Oncology CME, Projects in Knowledge CME, Rockpointe CME, MJH Life Sciences CME, Medical Educator Consortium, and HMP Education. Dr. Wakelee reports receiving grants from Arrys Therapeutics Research, AstraZeneca/Medimmune, Bristol-Myers Squibb, Genentech/Roche, Merck, Helsinn, Seagen, and Xcovery; and serving on the advisory board of Mirati (compensated)—ended November 2022, IOBiotech (compensated)—October 2023, Merck (NOT compensated), and Genentech/Roche/Bristol-Myers Squibb/AstraZeneca (NOT compensated). Dr. S.H. Lin reports receiving grants from STCube Pharmaceuticals, Beyond Spring, and Nektar Therapeutics; consulting fees from XRAD Therapeutics; serving on the advisory board of AstraZeneca; having stock/stock options from Apple, Google, Amazon, Tesla, Meta, Rivian, and CreatvMicrotech; and having other support from SEEK Diagnostics (co-founder). Dr. Patil reports receiving grants from Gilead Research Scholars and LUNGevity Foundation Award; consulting fees from AstraZeneca, Boehringer Ingelheim, Bicara, Daiichi, Janssen, Jazz Pharmaceuticals, Mirati Therapeutics, Pfizer, Sanofi, Regeneron, Roche/Genentech, Takeda, Gilead Research Scholars, and LUNGevity Foundation Award; and honorarium from Janssen. Dr. Bar reports receiving grants from Merck Sharp & Dohme, AstraZeneca, Roche, Bristol-Myers Squibb, Takeda, AbbVie, Bayer, Boehringer Ingelheim, and Pfizer; receiving consulting fees from AstraZeneca, Merck Sharp & Dohme, Boehringer Ingelheim, Roche, Bristol-Myers Squibb, Takeda, AbbVie, Pfizer, Bayer, and VBL; and having leadership role from Lung Ambition Consortium, Israel Lung Cancer Group, and IASLC committee. Dr. Marron receives grants from Regeneron, Bristol-Myers Squibb, Merck, Boehringer Ingelheim, NCI, and Cancer Research Institute; and serving on the advisory board of AbbVie, Celldex, and Rockefeller University. Dr. Yu receives grants/contracts from AstraZeneca, Pfizer, Daiichi Cullinan Oncology, Janssen, Novartis, Blueprint med, Black Diamond, and Systimmune and consulting fees from AstraZeneca, Daiichi, Taiho, Takeda, Janssen, Amgen, AbbVie, Novocure, and Ipsen. Dr. Owen receives grants/contracts from Bristol-Myers Squibb, Merck, Palobiofarma, Genentech, Onc.AI, and Pfizer; and travel support from Amgen, AstraZeneca, and Genentech. Rocha receives grants/contracts from SEOM, ESMO Fellowship, and AECC; and travel support from Merck Sharp & Dohme, AstraZeneca, and Bristol-Myers Squibb. Dr. Arriola receives grants/contracts from AstraZeneca and Bristol-Myers Squibb; honorarium from Eli Lilly, AstraZeneca, Roche, Takeda, Merck Sharp & Dohme, Pfizer, Janssen, and Bristol-Myers Squibb; and travel support from AstraZeneca, Roche, and Pfizer. Dr. Cheng receives grants/contracts from AstraZeneca and Genentech; and serving on the advisory board of Janssen, G1 Therapeutics, and AstraZeneca. Dr. Parikh receives consulting fees from Jazz Pharmaceuticals, Guardant Health, and AstraZeneca; and honorarium from MJH Life Sciences. Dr. Harris receives grants/contract from NIH P30CA062203, the UC Irvine Comprehensive Cancer Center using UCI Anti-Cancer Challenge Grant, and ACS Seed Grant 129801-IRG-16-187-13-IRG; and serving on the advisory board of UC Irvine as DSMB member. Dr. Nagasaka receives consulting fees from Caris Life Sciences; honorarium/speaker fees from AstraZeneca, Daiichi, Novartis, EMD Serono self, Pfizer, Eli Lilly, Genentech, Regeneron, Takeda, Janssen, Blueprint, and Mirati; travel support from AnHeart Therapeutics; and stock/stock options from Mbrace Therapeutics. Dr. Valazquez receives grants/contracts from ASCO, American Association for Cancer Research (AACR), LUNGevity, NIA P30AG015272, NCI 5U54CA242646-03 Conquer Cancer and Niarchos Foundation, UCSF Clinical Practice Group, and AAMC; consulting fees from AstraZeneca, Merus, Novocure, and Cadence Communications & Research; and having stock/stock options from Corbus Pharmaceuticals. Dr. J.J. Lin receives grants/contracts from Hengrui Therapeutics, Turning Point Therapeutics, Neon Therapeutics, Relay Therapeutics, Bayer, Elevation Oncology, Roche, Linnaeus Therapeutics, Nuvalent, and Novartis; consulting fees from Genentech, C4 Therapeutics, Blueprint Medicines, Nuvalent, Bayer, Elevation Oncology, Novartis, Mirati Therapeutics, AnHeart Therapeutics, Takeda, CLaiM Therapeutics, Regeneron, Pfizer, Turning Point Therapeutics, Daiichi Sankyo, AstraZeneca, and Merus. Dr. Piotrowska receives grants/contracts from Novartis, Takeda, Spectrum, AstraZeneca, Tesaro/GlaxoSmithKline, Cullinan Oncology, Daiichi Sankyo, AbbVie, Janssen, and Blueprint; consulting fees from Taiho, Janssen, Takeda, AstraZeneca, Cullinan Oncology, C4 Therapeutics, Jazz Pharmaceuticals, and Blueprint; and honorarium from Daiichi Sankyo, Janssen, and Eli Lilly (honoraria for nonpromotional educational events). Dr. Reuss receives grants/contracts from Genentech/Roche, Verastem, Nuvalent, and LUNGevity Foundation; consulting fees from Genentech/Roche, Sanofi/Genzyme, Personalis, Guardant, AstraZeneca, Bristol-Myers Squibb, Arcus, AbbVie, Daiichi Sankyo, Catalym, Seagen, and Gilead; and honorarium from AstraZeneca and Merck. Dr. Baena Espinar receives consulting fees from AstraZeneca, Roche, and Merck Sharp & Dohme; honorarium from AstraZeneca, Roche, and Merck Sharp & Dohme; payment for expert testimony from Roche; and travel support from Roche and Janssen. Leal receives research funding to institution from Pfizer, Advaxis, and Bayer, outside the submitted work. Dr. Mak receives grants/contracts from ViewRay; consulting fees from AstraZeneca, Novartis, and Sio Capital Management; and other support from Founder of HealthAI. Dr. Naqash receives grants/contracts from SWOG Hope Foundation and FDA Broad Agency Contract; serving on the advisory board of JCO Precision Oncology; receiving travel support from SITC/American Association for Cancer Research (AACR)/Conquer Cancer Foundation/BinayTara Foundation and Foundation Med/Caris Life Sciences, and Jazz Pharmaceuticals; and funding to institution for trials from Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals, Immunophotonics, and Selexine. Dr. Goldberg receives grants/contracts from AstraZeneca, Boehringer Ingelheim, and Mirati; and serving on the advisory board of AstraZeneca, Bristol-Myers Squibb, Amgen, Sanofi, Genzyme, Daiichi Sankyo, Regeneron, Takeda, Janssen, Summit, and Merck. The remaining authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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3. Real-World Outcomes With Lurbinectedin in Second-Line Setting and Beyond for Extensive Stage Small Cell Lung Cancer.
- Author
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Desai A, Smith CJ, Ashara Y, Orme JJ, Zanwar S, Potter A, Hocum C, Moffett JN, Schwecke AJ, Manochakian R, Lou Y, Zhao Y, Ernani V, Savvides P, Molina J, Dimou A, Mansfield AS, Parikh K, and Leventakos K
- Subjects
- Humans, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Small Cell Lung Carcinoma pathology, Lung Neoplasms pathology
- Abstract
Background: Lurbinectedin has emerged as a potential treatment option for relapsed small cell lung cancer (SCLC). While clinical trials have demonstrated its efficacy and safety, real-world data are limited. This study aimed to evaluate the safety and efficacy of lurbinectedin in a real-world setting, focusing on its use as a second-line agent and beyond in SCLC patients., Methods: A retrospective analysis was conducted on 90 patients who received lurbinectedin between June 2020 and June 2022 within the Mayo Clinic Health System. Of these, 50 patients received lurbinectedin as a second-line agent, and 14 patients received it as a third-line or later agent. The primary outcomes assessed were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events., Results: Lurbinectedin was generally well tolerated in this real-world cohort, with a median OS of 5.1 months in the second-line cohort and 5.6 months in the third-line or later cohort. Median PFS was 2.1 months in the second-line cohort and 3.4 months in the third-line or later cohort. Adverse events were manageable, with the most common being neutropenia, anemia, fatigue, and febrile neutropenia. No treatment-related deaths or grade 5 toxicities were reported., Conclusion: This real-world study provides valuable insights into the safety and efficacy of lurbinectedin in relapsed SCLC. Lurbinectedin demonstrated modest efficacy and a comparable safety profile to that observed in clinical trials. However, outcomes for relapsed SCLC remain suboptimal, particularly for patients with a shorter chemotherapy-free interval and central nervous system metastases., Competing Interests: Disclosure A.D: Advisory board: Amgen, Sanofi. C.S, Y.A, J.O, S.Z, A.P, C.H, N.M, A.S, J.M, Y.Z, P.S, K.P: Reports no relevant conflicts of interest. R.M: Consulting/advisory board for: AstraZeneca, Turning points, Janssen, Takeda, Y.L: Advisory board: AstraZeneca Pharmaceuticals, Janssen Pharmaceutical, Lilly Oncology, Turning point therapeutics, Consultant: AstraZeneca, Honorarium: clarion health care, Research Funding Support: Merck, MacroGenics, Tolero Pharmaceuticals, AstraZeneca, Vaccinex, Blueprint Medicines, Harpoon Therapeutics, Sun Pharma Advanced Research, Bristol-Myers Squibb, Kyowa Pharmaceuticals, Tesaro, Bayer HealthCare, Mirati Therapeutics, Daiichi Sankyo, V.E: Consulting/advisory board for: AstraZeneca, Daiichi Sanyo, Jazz Pharmaceuticals, Bayer, Pfizer, and Novocure, A.D: Advisory board: TP Therapeutics, Guardant Health, Chromacode, Anheart Therapeutics., A.S.M: is supported by a Mark Foundation ASPIRE Award, NCI R21 CA251923, and Department of Defense W81XWH-22-1-0021 Concept Award. Advisory Boards: AbbVie, AstraZeneca, BeiGene, BMS, Genentech, Inc., Janssen; Travel support and honoraria from Shanghai Roche Pharmaceuticals Ltd., and is non-remunerated member of the Mesothelioma Applied Research Foundation and Friends of Patan Hospital Board of Directors. K.L: consulting activities with Boehringer Ingelheim Pharmaceuticals, Amgen, AstraZeneca, Targeted Oncology, Takeda, Jazz Pharmaceuticals, Mirati Therapeutics, Janssen, and Regeneron; CME activities with OncLive and MJH Life Sciences; Research support (to institution) from AstraZeneca and Mirati Therapeutics.Clinical trial support: Novartis, Syntrix Therapeutics, Sorrento Therapeutics, Anheart Therapeutics, Merck; Honoraria: Roche/Genentech, Intellisphere., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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4. Time from immune checkpoint inhibitor to sotorasib use correlates with risk of hepatotoxicity in non-small cell lung cancer: A brief report.
- Author
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Desai A, Rakshit S, Bansal R, Ashara Y, Potter A, Manochakian R, Lou Y, Zhao Y, Ernani V, Savvides P, Schwecke A, Moffett N, Hocum C, Leventakos K, Adjei A, Marks R, Molina J, Mansfield AS, Chen ZM, and Dimou A
- Subjects
- Humans, Immune Checkpoint Inhibitors, Proto-Oncogene Proteins p21(ras), Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Chemical and Drug Induced Liver Injury epidemiology, Chemical and Drug Induced Liver Injury etiology
- Abstract
Introduction: We evaluated the risk factors and outcomes for patients who experienced hepatotoxicity after use of sotorasib in KRAS G12C mutated NSCLC., Methods: Retrospective review of medical records of patients with KRAS G12C mutated NSCLC who received sotorasib between May 28th, 2021, and December 31st, 2021 across all Mayo Clinic sites, with follow up until December 31st, 2022., Results: Thirty-one patients received sotorasib as standard of care treatment. Grade 3 or higher hepatoxicity was seen in 32% (10/31) patients presenting at a median of 51 days (range, 27-123) of sotorasib initiation. Baseline demographics were comparable between patients with and without ≥grade 3 hepatotoxicity, except for presence of CNS metastases and time from prior immune checkpoint inhibitor (ICI) treatment. Improvement in liver tests was observed in all patients after stopping sotorasib, and it was restarted at a lower dose in 8 patients. Despite dose reduction, hepatotoxicity requiring sotorasib discontinuation occurred in 2 patients. Twenty-eight of 31 patients had received prior ICI. Median time from prior ICI therapy was 69 days (range, 4-542). Rates of ≥grade 3 hepatoxicity were 75% (3/4), 64% (7/11) and 0% (0/13) for patients who received ICI within 30 days, 31-90 days and >90 days. None of the 3 patients without prior ICI exposure developed hepatoxicity. The median PFS and OS were 3.9 months and 9.9 months respectively., Conclusion: One-third of patients developed grade 3 or higher sotorasib induced hepatotoxicity. Risk of hepatotoxicity was higher in patients who received sotorasib within 90 days of ICI treatment., Competing Interests: Declaration of Competing Interest A.D.: Consulting/advisor board for: Amgen, and Sanofi; S.R: None; R.B: None; C.S: None; Y.A: None A.P: None; R.M: Consulting/advisory board for: AstraZeneca, Turning Point Therapeutics, Janssen, Takeda ; Y.L: Consulting/advisory board for: AstraZeneca Pharmaceuticals, Janssen Pharmaceutical, Lilly Oncology, Turning point therapeutics, Honoraria: clarion health care, Research Funding Support: Merck, MacroGenics, Tolero Pharmaceuticals, AstraZeneca, Vaccinex, Blueprint Medicines, Harpoon Therapeutics, Sun Pharma Advanced Research, Bristol-Myers Squibb, Kyowa Pharmaceuticals, Tesaro, Bayer HealthCare, Mirati Therapeutics, Daiichi Sankyo; Y.Z: None; V.E: Consulting/advisory board for: AstraZeneca, Daiichi Sanyo, Jazz Pharmaceuticals, Bayer, Pfizer, and Novocure; P.S: None; A.S: None; N.M: None; C.H: None; K.L: Consulting/advisory board: Boehringer Ingelheim Pharmaceuticals, Amgen, AstraZeneca, Targeted Oncology, Takeda, Jazz Pharmaceuticals, Mirati Therapeutics, Janssen, and Regeneron. CME activities: OncLive and MJH Life Sciences. Research support (to institution): AstraZeneca and Mirati Therapeutics; A.A: None; J.M: None; AMS: Direct research funding: National Cancer institute, Department of Defense, Mark Foundation, Novartis, and Verily; Honoraria to institution for participation in advisory boards: AbbVie, BeiGene, BMS, Genentech, Inc., Janssen; Travel support: Shanghai Roche, and non-remunerated member of the Mesothelioma Applied Research Foundation Board of Directors and Friends of Patan Hospital.; Z.C: None; A.D: Advisory board: TP Therapeutics, Guardant Health, Chromacode, Anheart Therapeutics. Clinical trial support: Novartis, Syntrix Therapeutics, Sorrento Therapeutics, Anheart Therapeutics, Merck; Honoraria: Roche/Genentech, Intellisphere., (Copyright © 2023. Published by Elsevier Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
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