10 results on '"Ramji Z"'
Search Results
2. Development of new and accurate measurement devices (TruSlice and TruSlice Digital) for use in histological dissection: an attempt to improve specimen dissection precision
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Orchard, G. E., primary, Shams, M., additional, Nwokie, T., additional, Bulut, C., additional, D'Amico, C., additional, Gabriel, J., additional, Ramji, Z., additional, Georgaki, A., additional, Neichcial, A., additional, Shams, F., additional, Neesam, H., additional, Haine, N., additional, and Brewer, C., additional
- Published
- 2015
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3. A population-based analysis of the impact of 1 vs. 2 doses of mitomycin on patterns of failure of anal cancer patients treated with concurrent chemoradiotherapy.
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Joseph K, Al Habsi Z, Abraham A, Elangovan A, Ghosh S, Pham T, Shreekumar D, Ramji Z, Paulson K, Tankel K, Usmani N, Severin D, Schiller D, Wong C, Mulder K, Karachiwala H, Doll C, King K, and Nijjar T
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Carcinoma, Squamous Cell therapy, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell drug therapy, Treatment Failure, Adult, Antibiotics, Antineoplastic therapeutic use, Antibiotics, Antineoplastic administration & dosage, Aged, 80 and over, Retrospective Studies, Disease-Free Survival, Mitomycin administration & dosage, Mitomycin therapeutic use, Anus Neoplasms therapy, Anus Neoplasms pathology, Anus Neoplasms mortality, Chemoradiotherapy methods, Fluorouracil administration & dosage, Neoplasm Recurrence, Local
- Abstract
Purpose: We report the impact of 1 vs. 2 doses of mitomycin-C (MMC) based chemoradiation (CRT) on patterns of treatment failure and long-term patient outcomes in anal squamous cell carcinoma (ASCC) and the predictors for locoregional failure (LRF) and distant metastasis (DM)., Methods: In this population-based study, we identified all patients with anal cancer in our province treated radically with radiation and concurrent 5-Fluorouracil (5FU) and 1 vs. 2 doses of MMC between the years 2000-2019. The primary outcomes analyzed were locoregional recurrence (LRR), disease free survival (DFS), ASCC cancer-specific survival (ASCC-CSS) and overall survival (OS)., Results: 451 patients were identified. 272 (60%) patients received 1 cycle of MMC (MMC1) and 179 (40%) received 2 cycles (MMC2) as part of the CRT regimen. The median follow-up was 57 (36-252) and 97 (38-239) months for MMC1 and MMC2, respectively. Cox Regression analysis showed stage IIIb and IIIc were associated with worse locoregional recurrence free survival (RFS) (HR=2.851, p=<0.001) and distant RFS (HR=3.391, p=<0.001). Similarly, stage IIIb and IIIc patients had poorer DFS (HR 3.439, p=<0.001), ASCC-SS (HR 3.729, p=<0.001) and OS (2.230, p=<0.001). The use of MMC2 showed a positive impact on improved ASCC-SS (HR 0.569, p=0.029) and distant RFS (HR 0.555, p=0.040) in patients with stage IIIb and IIIc., Conclusions: Our analysis showed that 1 vs. 2 cycles of MMC along with 5FU and radiation is associated with comparable treatment outcomes in general. However, in patients with stage IIIb and IIIc cancer, 2 doses of MMC were associated with improved ASCC-SS and distant DFS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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4. Association between treatment-emergent hypertension and survival with lenvatinib treatment for patients with hepatocellular carcinoma in the REFLECT study.
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Piscaglia F, Ikeda K, Cheng AL, Kudo M, Ikeda M, Breder V, Ryoo BY, Mody K, Ren M, Ramji Z, and Sung MW
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- Humans, Retrospective Studies, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Hypertension chemically induced, Hypertension complications, Hypertension drug therapy, Phenylurea Compounds, Quinolines
- Abstract
Background: Lenvatinib is approved as a first-line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment-emergent hypertension (CSTE-HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE-HTN on the efficacy and safety of lenvatinib in HCC., Methods: Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE-HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression-free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks., Results: A total of 212 patients in the lenvatinib arm developed CSTE-HTN, and 264 did not. CSTE-HTN first occurred at 3.7 weeks (median); the worst grade CSTE-HTN occurred at 4.1 weeks (median). No patients had life-threatening CSTE-HTN and/or died due to CSTE-HTN. Median OS was numerically longer in patients with versus without CSTE-HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621-1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696-1.089). Median PFS was similar between patients with and without CSTE-HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680-1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84-1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE-HTN (34.5%)., Conclusions: In this retrospective analysis, CSTE-HTN was associated with improved OS but not PFS. CSTE-HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2024
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5. Characterization of Tumor Responses in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib in the Phase 3 Randomized Trial: REFLECT.
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Finn RS, Qin S, Piscaglia F, Evans TRJ, Knox JJ, López López C, Ramji Z, Ren M, Mody K, Vogel A, and Kudo M
- Abstract
Introduction: In REFLECT, lenvatinib was noninferior to sorafenib in terms of overall survival (OS) in patients with unresectable hepatocellular carcinoma (uHCC; median 13.6 vs. 12.3 months; HR 0.92, 95% CI 0.79-1.06). The objective response rate (ORR) with lenvatinib was 18.8% by blinded independent imaging review (IIR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); per modified RECIST (mRECIST), the ORR was 40.6%. We sought to further characterize these tumor responses and explore ORR's importance among outcomes for patients with HCC., Methods: Efficacy assessments included all patients randomly assigned to receive lenvatinib treatment (if bodyweight ≥60 kg, 12 mg/day; if <60 kg, 8 mg/day). Time to first objective response (TTR) and duration of response (DOR) included patients who achieved a partial or complete tumor response. Tumors were assessed by IIR per RECIST v1.1 or mRECIST., Results: Four hundred seventy-eight patients were randomly assigned to receive lenvatinib. By IIR, 90 patients (18.8%) achieved an objective response per RECIST v1.1, and 194 (40.6%) had an objective response per mRECIST. Median TTR/DOR were 2.8 months/7.4 months in responders per RECIST v1.1, and 1.9 months/7.3 months in responders per mRECIST, respectively. Per baseline disease characteristics, ORRs by Child-Pugh score (A5/A6) were 21.2%/11.2% per RECIST v1.1 and 42.9%/33.6% per mRECIST, respectively. By baseline alpha-fetoprotein level (<400/≥400 ng/mL), ORRs were 21.4%/15.4% per RECIST v1.1 and 45.6%/33.8% per mRECIST, respectively. Incidences of treatment-related treatment-emergent adverse events were 98.9% in responders per RECIST v1.1 and 97.9% in responders per mRECIST., Conclusions: Responses were seen even in those patients with more severe disease at baseline. Tumor responses occurred early and were durable., Competing Interests: R.S.F. reports receiving institutional research funding from Pfizer, Bayer, Novartis, Eisai, Lilly, Merck, Bristol Myers Squibb, and Roche/Genentech; receiving a consulting or advisory role from Pfizer, Bayer, Novartis, Bristol Myers Squibb, Merck, Eisai, Lilly, Genentech/Roche, AstraZeneca, Exelixis, and C Stone Pharma; and providing expert testimony to Novartis. S.Q. has no relationships to disclose. F.P. reports receiving honoraria for advisory boards, lecturing, or consultancies from AstraZeneca, Bayer, Bracco, ESAOTE, EISAI, Exact Sciences, IPSEN, MSD, Roche, Samsung, and Siemens Healthineers. A.V. reports honoraria from Roche, Amgen, Lilly, Bristol Myers Squibb, MSD, Pierre Fabre, Ipsen, Janssen, Incyte, AstraZeneca/MedImmune, Sirtex Medical, Daiichi Sankyo, Advanced Accelerator Applications/Imaging Equipment Ltd., Terumo, Taiho Oncology, Eisai, BeiGene, Boehringer Pharma GmbH, GlaxoSmithKline, Boston Scientific, Sirtex Medical, and Servier; consulting or advisory role for Novartis, Lilly, Roche, Amgen, Baxalta, AstraZeneca, Eisai, BTG, Ipsen, Pierre Fabre, Terumo, Daiichi Sankyo, Sirtex Medical, Boehringer Pharma GmbH, Incyte, and Taiho Oncology; research funding from Novartis; and travel/accommodations/expenses from Roche, Ipsen, AstraZeneca, MSD, and Lilly. T.R.J.E. reports honoraria from Ascelia, AstraZeneca, Bicycle Therapeutics, Bristol Myers Squibb, Eisai, Medivir, Merck Sharp & Dohme, NuCana, and Roche/Genentech; consulting or advisory role for Karus Therapeutics; speakers’ bureau for AstraZeneca, Bristol Myers Squibb, Eisai, Medivir, Merck Sharp & Dohme, NuCana, Roche/Genentech, United Medical; research funding from Adaptimmune, Astellas Pharma, AstraZeneca, Athenex, Basilea, Beigene, Berg Pharma, Bicycle Therapeutics, BiolineRx, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Clovis Oncology, CytomX Therapeutics, Eisai, GlaxoSmithKline, Halozyme, Immunocore, iOnctura, Iovance Biotherapeutics, Janssen, Johnson & Johnson, Lilly, Medivir, Merck Serono, Merck Sharp & Dohme, MiNA Therapeutics, Modulate Pharma, Novartis, NuCana, Plexxikon, Roche/Genentech, Sanofi/Aventis, Sapience Therapeutics, Seagen, Sierra Pharma, Starpharma, UCB, Verastem, Vertex; expert testimony for Medivir; and travel/accommodations/expenses from Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, NuCana, and Pierre Fabre. J.J.K. reports honoraria from AstraZeneca, Roche Canada; consulting or advisory role for AstraZeneca/MedImmune, Incyte, Lilly, and Merck; research funding from AstraZeneca, Ipsen, and Merck; and expert testimony from AstraZeneca. CLL reports consulting or advisory fees and research funding from Bristol Myers Squibb, Merck Sharp & Dohme, Eisai Co. Ltd., Merck Group, Servier, Sanofi S.A., Roche/Genentech, Exelixis, Daiichi Sankyo, Ipsen, and AstraZeneca and consulting or advisory fees from Bayer AG, Amgen Inc., Novartis, and Pfizer Inc. Z.R. was an employee of Eisai Inc., Nutley, NJ, USA. M.R. is an employee of Eisai Inc., Nutley, NJ, USA. K.M. is an employee of Eisai Inc., Nutley, NJ, USA. M.K. reports consulting or advisory fees and research funding from Chugai, Roche, Eisai, AstraZeneca, Otsuka, Taiho, GE Healthcare, AbbVie, and EA Pharma and honoraria from Chugai, Eisai, Eli Lilly, and Takeda., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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6. Treatment-emergent antidrug antibodies related to PD-1, PD-L1, or CTLA-4 inhibitors across tumor types: a systematic review.
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Galle P, Finn RS, Mitchell CR, Ndirangu K, Ramji Z, Redhead GS, and Pinato DJ
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- Humans, CTLA-4 Antigen, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Immunotherapy methods, Immune Checkpoint Inhibitors therapeutic use, Neoplasms drug therapy
- Abstract
Background: Increased understanding of how the immune system regulates tumor growth has innovated the use of immunotherapeutics to treat various cancers. The impact of such therapies, including programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, on the production of antidrug antibodies (ADAs) and their impact on outcomes, is poorly understood. This study aims to evaluate the clinical trial evidence on ADA incidence associated with PD-1, PD-L1, and CTLA-4 inhibitors in the treatment of cancer and to assess associations between treatment administered, ADA incidence, and treatment outcomes., Methods: Embase
® , Medline® , and EBM Reviews were searched via the OVID® platform on February 15, 2022. Conference proceedings, clinical trial registries, and global regulatory and reimbursement body websites were also searched. Eligible publications included clinical trials enrolling patients receiving cancer treatment with either PD-1, PD-L1, or CTLA-4 reporting outcomes including incidence or prevalence of ADAs and the impact of immunogenicity on treatment safety and efficacy. Reference lists of eligible publications were also searched. The review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and evidence quality assessment was conducted using the appropriate Joanna Briggs Institute Critical Appraisal tool., Results: After screening 4160 records and reviewing 97 full publications, a total of 34 publications reporting on 68 trials were included. A further 41 relevant clinical trials were identified on ClinicalTrials.gov and a further 32 from searches of packaging inserts. In total, 141 relevant trials covering 15 different checkpoint inhibitors and 16 different tumor types were included. Across the included trials, atezolizumab was associated with the highest incidence of ADAs (29.6% of 639 patients), followed by nivolumab (11.2% of 2,085 patients). Combination checkpoint inhibitor treatment appeared to increase the rate of ADAs versus monotherapy. Only 17 trials reported on the impact of ADAs on treatment outcomes with mixed results for the impact of ADAs on treatment efficacy, safety, and pharmacokinetics., Conclusions: Checkpoint inhibitors for the treatment of cancer are immunogenic, with the incidence of treatment-emergent ADAs varying between individual therapies. It remains unclear what impact ADAs have on treatment outcomes., Competing Interests: Competing interests: KN and ZR were an employee of Eisai, USA. CRM and GSR of Mtech Access were paid consultants to Eisai. PG has received lecture fees and honoraria from BMS, Adaptimmune, AstraZeneca, Sirtex, MSD, Eisai, Ipsen, Bayer, Roche, Lilly, Boston Scientific, and Guerbet. DJP has received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, Eisai, Falk Foundation; travel expenses from BMS and Bayer Healthcare; consulting fees from Mina Therapeutics, Eisai, Roche, Ipsen, Mursla, Starpharma, Avamune, DaVolterra, and Astra Zeneca; and research funding (to institution) from MSD, GSK, and BMS. RSF has acted as a consultant to AstraZeneca, Bayer, BMS, CStone, Exelixis, Eisai, Merck, Pfizer, Roche/Genentech, and has received grants (to institution) from Bayer, BMS, Eisai, Merck, Pfizer, and Roche/Genentech., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2024
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7. A Phase 1b Study of Lenvatinib plus Pembrolizumab in Patients with Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116.
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Kudo M, Finn RS, Ikeda M, Sung MW, Baron AD, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Meyer T, Nagao S, Saito K, Mody K, Ramji Z, Dubrovsky L, and Llovet JM
- Abstract
Introduction: Lenvatinib (dosing for patients who weigh ≥60 kg was 12 mg/day; for patients who weigh <60 kg, the dose was 8 mg/day) plus pembrolizumab 200 mg once every 3 weeks demonstrated antitumor activity and a manageable safety profile in patients with first-line unresectable hepatocellular carcinoma (uHCC) in the open-label phase 1b Study 116/KEYNOTE-524 (primary analysis data cutoff date: October 31, 2019; median follow-up: 10.6 months). This analysis (updated data cutoff date: March 31, 2021) reports efficacy results from 17 months of additional follow-up time., Methods: 100 patients with uHCC were included in the primary analysis (median follow-up: 27.6 months). Endpoints included overall survival (OS), investigator-assessed progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) per modified RECIST. Landmark analyses of OS by the best response at 3 and 9 months were performed. Pembrolizumab antidrug antibodies (ADAs) and concentrations were also measured (cutoff date: August 7, 2020)., Results: ORR was 43.0% (95% CI 33.1-53.3%) and median DOR was 17.1 months (95% CI 6.9-19.3 months). Median PFS and OS were 9.3 months (95% CI 7.4-9.8 months) and 20.4 months (95% CI 14.4-25.9 months), respectively. No treatment-emergent ADAs were detected., Conclusion: Results show a sustained treatment effect with lenvatinib plus pembrolizumab in patients with uHCC in the first-line setting., Competing Interests: Masatoshi Kudo: honoraria – Eli Lilly, Bayer, Eisai, Chugai, Takeda, and AstraZeneca; grant – Taiho, Otsuka, EA Pharma, AbbVie, Eisai, Chugai, and GE Healthcare; and advisory consulting – Chugai, Roche, Eisai, and AstraZeneca. Richard S. Finn: consulting or advisory role – Pfizer, Bayer, Novartis, Bristol Myers Squibb, Merck, Eisai, Lilly, Genentech/Roche, AstraZeneca, Exelixis, and C Stone Pharma; research funding – Pfizer (Inst), Bayer (Inst), Novartis (Inst), Eisai (Inst), Lilly (Inst), Merck (Inst), Bristol Myers Squibb (Inst), and Roche/Genentech (Inst); and expert testimony – Novartis. Masafumi Ikeda: honoraria – Abbott Japan, Bayer Yakuhin, Bristol Myers Squibb Japan, Chugai Pharma, Eisai, Lilly Japan, Novartis, Taiho Pharmaceutical, Teijin Pharma, Yakult, Nihon Servier, AstraZeneca, MSD, Takeda, Astellas Pharma, AbbVie, Fujifilm Toyama Chemical, EA Pharma, Ono Pharmaceutical, Incyte Biosciences Japan, and Taisho Pharmaceutical; consulting or advisory role – Eisai, Novartis, Lilly Japan, Chugai Pharma, Ono Pharmaceutical, AstraZeneca, Nihon Servier, Takeda, and GlaxoSmithKline; and research funding – AstraZeneca (Inst), Bayer Yakuhin (Inst), Bristol Myers Squibb (Inst), Chugai Pharma (Inst), Eisai, Lilly Japan (Inst), Merck Biopharma (Inst), Delta-Fly Pharma (Inst), Novartis (Inst), Ono Pharmaceutical (Inst), Yakult (Inst), MSD (Inst), J-Pharma (Inst), Takeda (Inst), Pfizer (Inst), Chiome Bioscience (Inst), Merus N.V. (Inst), Nihon Servier (Inst), and Syneos Health (Inst). Max W. Sung: honoraria – Genentech and Bayer. Ari D. Baron: speakers’ bureau – Bristol Myers Squibb, Merck, Lilly, Amgen, Eisai, Johnson & Johnson, and AbbVie. Takuji Okusaka: honoraria – Meiji Seika Kaisha, Merck Sharp & Dohme, Shire, AbbVie, Eisai, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceuticals, Teijin Pharma, Lilly, Nippon Shinyaku, Servier, Novartis, Bayer, Pfizer, and Mundipharma; consulting or advisory role – Taiho Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Bristol Myers Squibb, AstraZeneca, and Eisai; research funding – Novartis (Inst), Eisai (Inst), Dainippon Sumitomo Pharma (Inst), Baxter (Inst), Lilly (Inst), Taiho Pharmaceutical (Inst), AstraZeneca (Inst), Chugai Pharma (Inst), Bristol Myers Squibb, and Merck Sharp & Dohme (Inst); and travel, accommodations, and expenses – Takara Bio. Masahiro Kobayashi: honoraria – Eisai Japan. Hiromitsu Kumada: honoraria – Merck Sharp & Dohme, Dainippon Sumitomo Pharma, AbbVie, Gilead Sciences, and Eisai. Shuichi Kaneko: honoraria – Merck Sharp & Dohme, Eisai, Gilead Sciences, Dainippon Sumitomo Pharma, Bayer, Bristol Myers Squibb, and Lilly; consulting or advisory role – Bayer, Merck Sharp & Dohme, Lilly, and Eisai; research funding – Merck Sharp & Dohme (Inst), Bayer (Inst), Chugai Pharma (Inst), and Eisai (Inst). Marc Pracht: consulting – BMS and Ipsen. Tim Meyer: consulting – Eisai, BMS, Adaptimmune, Ipsen, Roche, and AstraZeneca; grant funding – MSD. Satoshi Nagao, Kalgi Mody, and Zahra Ramji: employment – Eisai. Kenichi Saito: employment – Eisai; and patents, royalties, and other intellectual property – applying for patent for pharmaceutical composition. Leonid Dubrovsky: employment – Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Josep M. Llovet: research support – Eisai, Bristol Myers Squibb, Bayer Pharmaceuticals, Boehringer-Ingelheim, and Ipsen; and consultancy – Eisai, Merck, Bayer Pharmaceuticals, Bristol Myers Squibb, Celsion Corporation, Eli Lilly, Roche, Genentech, Ipsen, Glycotest, Nucleix, Biopharma, Sirtex, and AstraZeneca., (© 2023 The Author(s). Published by S. Karger AG, Basel.)
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- 2023
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8. Characterization and Management of Adverse Reactions in Patients With Unresectable Hepatocellular Carcinoma Treated With Lenvatinib.
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Jones A, Degregorio P, Sung MW, Ramji Z, Ren M, and Baron AD
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Aims: Advanced practice providers (APPs) play a vital role in monitoring for and managing adverse reactions (ARs). As lenvatinib ARs can resemble cirrhosis (commonly presenting with hepatocellular carcinoma [HCC]), APP input is important for timely detection and management of ARs and to promote medication adherence., Design: The goal of this post-hoc analysis of the REFLECT trial was to characterize key ARs associated with lenvatinib, and to discuss management strategies., Methods: In REFLECT, patients with unresectable HCC were randomized to either daily lenvatinib (12 mg/day for patients who weighed ≥ 60 kg or 8 mg/day for those < 60 kg) or sorafenib 400 mg twice daily. Adverse events in the lenvatinib arm were grouped into ARs (hypertension, fatigue, palmar-plantar erythrodysesthesia syndrome, proteinuria, and decreased appetite) per the United States Prescribing Information (USPI) for lenvatinib., Results: Key ARs in the lenvatinib arm ( n = 476) generally occurred within months of starting lenvatinib. Some cases of proteinuria, decreased appetite, and diarrhea were first reported at about 2 years of treatment., Conclusions: The onset of key ARs associated with lenvatinib treatment can be predicted and generally be managed (per the lenvatinib USPI and REFLECT) by withholding lenvatinib and resuming it at a reduced dose after the severity decreases. However, lenvatinib should generally be discontinued if the AR is life-threatening., Competing Interests: This study was sponsored by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Medical writing support was provided by Michael Venditto, PharmD, of Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Nutley, NJ, USA, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Ms. Jones and Ms. Degregorio have no conflicts of interest to disclose. Dr. Sung has served a consulting or advisory role for Bayer, Eisai, Exelixis, and Genentech. Ms. Ramji and Dr. Ren are employees of Eisai Inc. Dr. Baron has served on the speakers bureau for Lilly, Amgen, Eisai, Johnson & Johnson, AbbVie, Merck, and Bristol Myers Squibb., (© 2023 BroadcastMed LLC.)
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- 2023
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9. Lenvatinib in patients with unresectable hepatocellular carcinoma who progressed to Child-Pugh B liver function.
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Huynh J, Cho MT, Kim EJ, Ren M, Ramji Z, and Vogel A
- Abstract
Background: Lenvatinib is an approved first-line treatment for unresectable hepatocellular carcinoma (uHCC). We evaluated the safety and efficacy of lenvatinib versus sorafenib in patients with uHCC who deteriorated to Child-Pugh class B (CP-B) on treatment., Methods: We retrospectively evaluated patients from REFLECT who deteriorated to CP-B versus those who remained Child-Pugh class A (CP-A) within 8 weeks after randomization. Best overall response and objective response rate (ORR) per modified Response Evaluation Criteria In Solid Tumors (mRECIST) were assessed from baseline. Progression-free survival (PFS) per mRECIST and overall survival (OS) were assessed beginning at week 8., Results: Patients with CP-B versus CP-A classification receiving lenvatinib had ORRs of 28.3 and 42.9%, respectively; patients with CP-B versus CP-A classification receiving sorafenib had ORRs of 8.5 and 12.9%, respectively. Median PFS and OS (landmark analyses beginning at week 8) in patients receiving lenvatinib were 3.7 months [95% confidence interval (CI): 1.8-7.4] and 6.8 months (95% CI: 2.6-10.3) in the CP-B subgroup versus 6.5 months (95% CI: 5.6-7.4) and 13.3 months (95% CI: 11.6-16.1) in the CP-A subgroup, respectively. Median PFS and OS in patients receiving sorafenib were 0.5 months (95% CI: 0.1-3.6) and 4.5 months (95% CI: 2.9-6.1) in the CP-B subgroup versus 3.6 months (95% CI: 2.7-3.7) and 12.0 months (95% CI: 10.2-14.0) in the CP-A subgroup, respectively. The most common treatment-emergent adverse events in the lenvatinib cohort were hypertension (both subgroups) and decreased appetite (CP-B subgroup)., Conclusion: Results suggest that patients with uHCC whose liver function deteriorates to CP-B after initiation of therapy may continue to receive lenvatinib., Trial Registration: ClinicalTrials.gov, NCT01761266, https://clinicaltrials.gov/ct2/show/NCT01761266., Competing Interests: Competing interests: JH: No disclosures. MTC: Eisai: consulting and advisory board. EJ-HK: Eisai: advisory board, speakers bureau; Taiho: advisory board. MR: Employee of Eisai Inc. ZR: Employee of Eisai Inc. AV: Speaker, consultancy, and advisory role: Amgen, Roche, Bayer, Sanofi, BMS, Lilly, Novartis, Eisai, AstraZeneca, Merck, Incyte, Ipsen, PierreFabre, MSD, Sirtex, BTG, Servier, Terumo, GS, (© The Author(s), 2022.)
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- 2022
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10. Ankle Lead Arthropathy and Systemic Lead Toxicity Secondary to a Gunshot Wound After 49 Years: A Case Report.
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Ramji Z and Laflamme M
- Subjects
- Arthritis etiology, Arthrodesis, Foreign Bodies complications, Humans, Joint Diseases etiology, Lead blood, Male, Middle Aged, Synovial Membrane surgery, Ankle Joint surgery, Foreign Bodies surgery, Joint Diseases surgery, Lead toxicity, Wounds, Gunshot complications
- Abstract
Intra-articular bullet wounds have been found to cause both local and systemic consequences, in particular, when retained over many years. Only a few such cases have been described in published reports, each with different implications, depending on the joint involved and whether the patient experienced lead toxicity. We report the rare case of a 63-year-old male with lead arthropathy of the ankle secondary to a gunshot wound 49 years earlier. In addition to his severe tibiotalar arthritis, he presented with significantly elevated blood lead levels. Although he remained asymptomatic of lead toxicity, the patient was treated with preoperative chelator therapy and arthroscopic debridement, excision of accessible bullet fragments, and partial synovectomy to alleviate his ankle pain. However, he continued to experience ankle pain, and his blood lead levels remained elevated. He, therefore, underwent arthroscopic ankle arthrodesis with preoperative chelator therapy to prevent a further increase in blood lead levels secondary to surgical manipulation. Although lead arthropathy and toxicity secondary to retained intra-articular bullets has been documented in various joints during the past decades, to the best of our knowledge, the present case is the first adult case of an affected ankle reported in published English studies in 40 years. The standard of care has evolved since then, in particular, in regard to chelator therapy and the necessity for removal of intra-articular lead fragments to prevent further lead toxicity. The present case serves as an example of lead arthropathy of the ankle and highlights the importance of balancing the standard of care with symptomatic care to optimize patient well-being., (Copyright © 2017 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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