1,082 results on '"Finn, Richard S"'
Search Results
2. Effect of cross-platform gene-expression, computational methods on breast cancer subtyping in PALOMA-2 and PALLET studies
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Cheang, Maggie Chon U, Rimawi, Mothaffar, Johnston, Stephen, Jacobs, Samuel A., Bliss, Judith, Pogue-Geile, Katherine, Kilburn, Lucy, Zhu, Zhou, Schuster, Eugene F., Xiao, Hui, Swaim, Lisa, Deng, Shibing, Lu, Dongrui R., Gauthier, Eric, Tursi, Jennifer, Slamon, Dennis J., Rugo, Hope S., Finn, Richard S., and Liu, Yuan
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- 2024
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3. Author Correction: Hepatocellular carcinoma
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Llovet, Josep M., Kelley, Robin Kate, Villanueva, Augusto, Singal, Amit G., Pikarsky, Eli, Roayaie, Sasan, Lencioni, Riccardo, Koike, Kazuhiko, Zucman-Rossi, Jessica, and Finn, Richard S.
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- 2024
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4. Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
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Kim, Hyung-Don, Jung, Seyoung, Lim, Ho Yeong, Ryoo, Baek-Yeol, Ryu, Min-Hee, Chuah, Samuel, Chon, Hong Jae, Kang, Beodeul, Hong, Jung Yong, Lee, Han Chu, Moon, Deok-Bog, Kim, Ki-Hun, Kim, Tae Won, Tai, David, Chew, Valerie, Lee, Jeong Seok, Finn, Richard S., Koh, June-Young, and Yoo, Changhoon
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- 2024
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5. HCC EV ECG score: An extracellular vesicle‐based protein assay for detection of early‐stage hepatocellular carcinoma
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Sun, Na, Zhang, Ceng, Lee, Yi‐Te, Tran, Benjamin V, Wang, Jing, Kim, Hyoyong, Lee, Junseok, Zhang, Ryan Y, Wang, Jasmine J, Hu, Junhui, Zhang, Zhicheng, Alsudaney, Manaf S, Hou, Kuan‐Chu, Tang, Hubert, Zhang, Tiffany X, Liang, Icy Y, Zhou, Ziang, Chen, Mengxiang, Yeh, Angela Hsiao‐Jiun, Li, Wenyuan, Zhou, Xianghong Jasmine, Chang, Helena R, Han, Steven‐Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Noureddin, Mazen, Ayoub, Walid S, Kuo, Alexander, Sundaram, Vinay, Al‐Ghaieb, Buraq, Palomique, Juvelyn, Kosari, Kambiz, Kim, Irene K, Todo, Tsuyoshi, Nissen, Nicholas N, Tomasi, Maria Lauda, You, Sungyong, Posadas, Edwin M, Wu, James X, Wadehra, Madhuri, Sim, Myung‐Shin, Li, Yunfeng, Wang, Hanlin L, French, Samuel W, Lu, Shelly C, Wu, Lily, Pei, Renjun, Liang, Li, Yang, Ju Dong, Agopian, Vatche G, Tseng, Hsian‐Rong, and Zhu, Yazhen
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Liver Cancer ,Prevention ,Liver Disease ,Cancer ,Clinical Research ,Digestive Diseases ,Rare Diseases ,4.2 Evaluation of markers and technologies ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Good Health and Well Being ,Humans ,Carcinoma ,Hepatocellular ,Liver Neoplasms ,Biomarkers ,Tumor ,Extracellular Vesicles ,Membrane Proteins ,Electrocardiography ,Glypicans ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background and aimsThe sensitivity of current surveillance methods for detecting early-stage hepatocellular carcinoma (HCC) is suboptimal. Extracellular vesicles (EVs) are promising circulating biomarkers for early cancer detection. In this study, we aim to develop an HCC EV-based surface protein assay for early detection of HCC.Approach and resultsTissue microarray was used to evaluate four potential HCC-associated protein markers. An HCC EV surface protein assay, composed of covalent chemistry-mediated HCC EV purification and real-time immuno-polymerase chain reaction readouts, was developed and optimized for quantifying subpopulations of EVs. An HCC EV ECG score, calculated from the readouts of three HCC EV subpopulations ( E pCAM + CD63 + , C D147 + CD63 + , and G PC3 + CD63 + HCC EVs), was established for detecting early-stage HCC. A phase 2 biomarker study was conducted to evaluate the performance of ECG score in a training cohort ( n = 106) and an independent validation cohort ( n = 72).Overall, 99.7% of tissue microarray stained positive for at least one of the four HCC-associated protein markers (EpCAM, CD147, GPC3, and ASGPR1) that were subsequently validated in HCC EVs. In the training cohort, HCC EV ECG score demonstrated an area under the receiver operating curve (AUROC) of 0.95 (95% confidence interval [CI], 0.90-0.99) for distinguishing early-stage HCC from cirrhosis with a sensitivity of 91% and a specificity of 90%. The AUROCs of the HCC EV ECG score remained excellent in the validation cohort (0.93; 95% CI, 0.87-0.99) and in the subgroups by etiology (viral: 0.95; 95% CI, 0.90-1.00; nonviral: 0.94; 95% CI, 0.88-0.99).ConclusionHCC EV ECG score demonstrated great potential for detecting early-stage HCC. It could augment current surveillance methods and improve patients' outcomes.
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- 2023
6. Effect of palbociclib plus endocrine therapy on time to chemotherapy across subgroups of patients with hormone receptor‒positive/human epidermal growth factor receptor 2‒negative advanced breast cancer: Post hoc analyses from PALOMA-2 and PALOMA-3
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Rugo, Hope S, Im, Seock-Ah, Joy, Anil A, Shparyk, Yaroslav, Walshe, Janice M, Sleckman, Bethany, Loi, Sherene, Theall, Kathy Puyana, Kim, Sindy, Huang, Xin, Bananis, Eustratios, Mahtani, Reshma, Finn, Richard S, and Diéras, Véronique
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Cancer ,Clinical Trials and Supportive Activities ,Breast Cancer ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,Female ,Humans ,Antineoplastic Combined Chemotherapy Protocols ,Breast Neoplasms ,Fulvestrant ,Receptor ,ErbB-2 ,Advanced breast cancer ,Chemotherapy ,Palbociclib ,Progression -free survival ,Safety ,Receptor ,erbB-2 ,Progression-free survival ,Clinical Sciences ,Public Health and Health Services ,Oncology & Carcinogenesis - Abstract
BackgroundPrevious analyses from the PALOMA-2 and PALOMA-3 studies showed that palbociclib (PAL) plus endocrine therapy (ET) prolongs time to first subsequent chemotherapy (TTC) versus placebo (PBO) plus ET in the overall population of patients with hormone receptor‒positive/human epidermal growth factor receptor 2‒negative (HR+/HER2-) advanced breast cancer (ABC). Here, we evaluated TTC in relevant patient subgroups.MethodsThese post hoc analyses evaluated TTC by subgroup using data from 2 randomized, phase 3 studies of women with HR+/HER2- ABC. In PALOMA-2, postmenopausal patients previously untreated for ABC were randomized 2:1 to receive PAL (125 mg/day, 3/1-week schedule) plus letrozole (LET; 2.5 mg/day; n = 444) or PBO plus LET (n = 222). In PALOMA-3, premenopausal or postmenopausal patients whose disease had progressed after prior ET were randomized 2:1 to receive PAL (125 mg/day, 3/1-week schedule) plus fulvestrant (FUL; 500 mg; n = 347) or PBO plus FUL (n = 174).ResultsFirst subsequent chemotherapy was received by 35.5% and 56.2% in PALOMA-2 and PALOMA-3 after progression on palbociclib plus ET or placebo plus ET. Across all subgroups analyzed, the median progression-free survival (PFS) was longer in the PAL plus ET arm than the PBO plus ET arm. TTC was longer with PAL plus ET versus PBO plus ET across the same patient subgroups in both studies.ConclusionsAcross all subgroups, PAL plus ET versus PBO plus ET had longer median PFS and resulted in prolonged TTC in both the PALOMA-2 and PALOMA-3 studies. Pfizer Inc (NCT01740427, NCT01942135).
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- 2022
7. Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment
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Glaviano, Antonino, Wander, Seth A., Baird, Richard D., Yap, Kenneth C.-H., Lam, Hiu Yan, Toi, Masakazu, Carbone, Daniela, Geoerger, Birgit, Serra, Violeta, Jones, Robert H., Ngeow, Joanne, Toska, Eneda, Stebbing, Justin, Crasta, Karen, Finn, Richard S., Diana, Patrizia, Vuina, Karla, de Bruin, Robertus A.M., Surana, Uttam, Bardia, Aditya, and Kumar, Alan Prem
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- 2024
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8. Nonalcoholic steatohepatitis-related hepatocellular carcinoma: pathogenesis and treatment
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Llovet, Josep M., Willoughby, Catherine E., Singal, Amit G., Greten, Tim F., Heikenwälder, Mathias, El-Serag, Hashem B., Finn, Richard S., and Friedman, Scott L.
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- 2023
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9. Clinical Review on the Management of Hormone Receptor–Positive Metastatic Breast Cancer
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McAndrew, Nicholas P and Finn, Richard S
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Estrogen ,Breast Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Antineoplastic Combined Chemotherapy Protocols ,Breast Neoplasms ,Female ,Humans ,Letrozole ,Quality of Life ,Oncology and carcinogenesis - Abstract
The natural history of hormone receptor-positive breast cancer tends to be more favorable than other subtypes such as human epidermal growth factor receptor 2-amplified and triple-negative. In addition, the natural dependence on steroid hormone signaling has allowed for therapeutic targeting of this pathway and significant improvements in survival while maintaining quality of life: the two main goals in management of the disease. The sequential use of endocrine agents including the selective estrogen receptor modulators (tamoxifen), aromatase inhibitors (letrozole, anastrozole, and exemestane) and the selective estrogen receptor degrader fulvestrant has been the backbone of management for years. In the past decade, the introduction of molecularly targeted agents against intracellular targets such as mammalian target of rapamycin (everolimus), cyclin-dependent kinases 4 and 6 (palbociclib, ribociclib, and abemaciclib), and phosphatidylinositol 3-kinase (alpelisib) has offered patients effective nonchemotherapy-based options, which are improving outcomes. Although knowledge gaps still exist in regard to the optimal sequencing of these new regimens, they have expanded our repertoire of options for patients and have shifted the need for cytotoxic chemotherapy and its associated complications to later lines. Still, formatting a plan for these patients includes taking into account traditional prognostic factors such as menopausal status, previous treatments, disease-free interval for those patients with early breast cancer that has recurred, and tumor burden. To assist in developing this treatment plan, we will review the current data with systemic agents in the management of these patients.
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- 2022
10. Real-world study of overall survival with palbociclib plus aromatase inhibitor in HR+/HER2− metastatic breast cancer
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Rugo, Hope S, Brufsky, Adam, Liu, Xianchen, Li, Benjamin, McRoy, Lynn, Chen, Connie, Layman, Rachel M, Cristofanilli, Massimo, Torres, Mylin A, Curigliano, Giuseppe, Finn, Richard S, and DeMichele, Angela
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Breast Cancer ,Clinical Trials and Supportive Activities ,Clinical Research ,Rehabilitation ,Cancer ,Evaluation of treatments and therapeutic interventions ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,6.1 Pharmaceuticals - Abstract
Data on real-world effectiveness of cyclin-dependent kinase 4/6 inhibitor combination therapy versus endocrine therapy alone are limited. The Flatiron Health Analytic Database was used to assess overall survival (OS) in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC) treated with first-line palbociclib plus an aromatase inhibitor (AI) versus an AI alone in routine US clinical practice. In total, 2888 patients initiated treatment during February 3, 2015-March 31, 2020, with a potential ≥6-month follow-up (cutoff date, September 30, 2020). After stabilized inverse probability treatment weighting, median OS (95% CI) is significantly longer among palbociclib versus AI recipients (49.1 [45.2-57.7] versus 43.2 [37.6-48.0] months; hazard ratio, 0.76 [95% CI, 0.65-0.87]; P
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- 2022
11. Evolution of Systemic Therapy in Advanced Hepatocellular Carcinoma
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Bejjani, Anthony and Finn, Richard S.
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- 2024
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12. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of hepatocellular carcinoma
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Greten, Tim F, Abou-Alfa, Ghassan K, Cheng, Ann-Lii, Duffy, Austin G, El-Khoueiry, Anthony B, Finn, Richard S, Galle, Peter R, Goyal, Lipika, He, Aiwu Ruth, Kaseb, Ahmed O, Kelley, Robin Kate, Lencioni, Riccardo, Lujambio, Amaia, Hrones, Donna Mabry, Pinato, David J, Sangro, Bruno, Troisi, Roberto I, Woods, Andrea Wilson, Yau, Thomas, Zhu, Andrew X, and Melero, Ignacio
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Clinical Trials and Supportive Activities ,Liver Cancer ,Digestive Diseases ,Rare Diseases ,Vaccine Related ,Cancer ,Clinical Research ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Patient Safety ,Immunization ,Good Health and Well Being ,Carcinoma ,Hepatocellular ,Guidelines as Topic ,Humans ,Immunotherapy ,Liver Neoplasms ,antineoplastic protocols ,immunotherapy ,guidelines as topic ,liver neoplasms ,Oncology and carcinogenesis - Abstract
Patients with advanced hepatocellular carcinoma (HCC) have historically had few options and faced extremely poor prognoses if their disease progressed after standard-of-care tyrosine kinase inhibitors (TKIs). Recently, the standard of care for HCC has been transformed as a combination of the immune checkpoint inhibitor (ICI) atezolizumab plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was shown to offer improved overall survival in the first-line setting. Immunotherapy has demonstrated safety and efficacy in later lines of therapy as well, and ongoing trials are investigating novel combinations of ICIs and TKIs, in addition to interventions earlier in the course of disease or in combination with liver-directed therapies. Because HCC usually develops against a background of cirrhosis, immunotherapy for liver tumors is complex and oncologists need to account for both immunological and hepatological considerations when developing a treatment plan for their patients. To provide guidance to the oncology community on important concerns for the immunotherapeutic care of HCC, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew on the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for HCC, including diagnosis and staging, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence- and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with HCC.
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- 2021
13. Pharmacodynamic Biomarkers Predictive of Survival Benefit with Lenvatinib in Unresectable Hepatocellular Carcinoma: From the Phase III REFLECT StudyBiomarker Analysis Following Lenvatinib in Unresectable HCC
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Finn, Richard S, Kudo, Masatoshi, Cheng, Ann-Lii, Wyrwicz, Lucjan, Ngan, Roger KC, Blanc, Jean-Frederic, Baron, Ari D, Vogel, Arndt, Ikeda, Masafumi, Piscaglia, Fabio, Han, Kwang-Hyub, Qin, Shukui, Minoshima, Yukinori, Kanekiyo, Michio, Ren, Min, Dairiki, Ryo, Tamai, Toshiyuki, Dutcus, Corina E, Ikezawa, Hiroki, Funahashi, Yasuhiro, and Evans, Thomas R Jeffry
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Clinical Trials and Supportive Activities ,Clinical Research ,Antineoplastic Agents ,Biomarkers ,Tumor ,Carcinoma ,Hepatocellular ,Humans ,Liver Neoplasms ,Phenylurea Compounds ,Predictive Value of Tests ,Quinolines ,Sorafenib ,Survival Rate ,Oncology & Carcinogenesis ,Clinical sciences ,Oncology and carcinogenesis - Abstract
PurposeIn REFLECT, lenvatinib demonstrated an effect on overall survival (OS) by confirmation of noninferiority to sorafenib in unresectable hepatocellular carcinoma. This analysis assessed correlations between serum or tissue biomarkers and efficacy outcomes from REFLECT.Experimental designSerum biomarkers (VEGF, ANG2, FGF19, FGF21, and FGF23) were measured by ELISA. Gene expression in tumor tissues was measured by the nCounter PanCancer Pathways Panel. Pharmacodynamic changes in serum biomarker levels from baseline, and associations of clinical outcomes with baseline biomarker levels, were evaluated.ResultsFour hundred and seven patients were included in the serum analysis set (lenvatinib n = 279, sorafenib n = 128); 58 patients were included in the gene-expression analysis set (lenvatinib n = 34, sorafenib n = 24). Both treatments were associated with increases in VEGF; only lenvatinib was associated with increases in FGF19 and FGF23 at all time points. Lenvatinib-treated responders had greater increases in FGF19 and FGF23 versus nonresponders at cycle 4, day 1 (FGF19: 55.2% vs. 18.3%, P = 0.014; FGF23: 48.4% vs. 16.4%, P = 0.0022, respectively). Higher baseline VEGF, ANG2, and FGF21 correlated with shorter OS in both treatment groups. OS was longer for lenvatinib than sorafenib [median, 10.9 vs. 6.8 months, respectively; HR, 0.53; 95% confidence interval (CI), 0.33-0.85; P-interaction = 0.0397] with higher baseline FGF21. In tumor tissue biomarker analysis, VEGF/FGF-enriched groups showed improved OS with lenvatinib versus the intermediate VEGF/FGF group (HR, 0.39; 95% CI, 0.16-0.91; P = 0.0253).ConclusionsHigher baseline levels of VEGF, FGF21, and ANG2 may be prognostic for shorter OS. Higher baseline FGF21 may be predictive for longer OS with lenvatinib compared with sorafenib, but this needs confirmation.
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- 2021
14. Covalent Chemistry‐Mediated Multimarker Purification of Circulating Tumor Cells Enables Noninvasive Detection of Molecular Signatures of Hepatocellular Carcinoma
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Sun, Na, Lee, Yi‐Te, Kim, Minhyung, Wang, Jasmine J, Zhang, Ceng, Teng, Pai‐Chi, Qi, Dongping, Zhang, Ryan Y, Tran, Benjamin V, Lee, Yue Tung, Ye, Jinglei, Palomique, Juvelyn, Nissen, Nicholas N, Han, Steven‐Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Posadas, Edwin M, Liang, Li, Pei, Renjun, Yang, Ju Dong, You, Sungyong, Agopian, Vatche G, Tseng, Hsian‐Rong, and Zhu, Yazhen
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Digestive Diseases ,Genetics ,Prevention ,Rare Diseases ,Liver Disease ,Biotechnology ,Cancer ,Clinical Research ,Liver Cancer ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Good Health and Well Being ,circulating tumor cells ,click chemistry ,hepatocellular carcinoma ,nanosubstrate ,transcriptome profiling - Abstract
Transcriptomic profiling of tumor tissues introduces a large database, which has led to improvements in the ability of cancer diagnosis, treatment, and prevention. However, performing tumor transcriptomic profiling in the clinical setting is very challenging since the procurement of tumor tissues is inherently limited by invasive sampling procedures. Here, we demonstrated the feasibility of purifying hepatocellular carcinoma (HCC) circulating tumor cells (CTCs) from clinical patient samples with improved molecular integrity using Click Chips in conjunction with a multimarker antibody cocktail. The purified CTCs were then subjected to mRNA profiling by NanoString nCounter platform, targeting 64 HCC-specific genes, which were generated from an integrated data analysis framework with 8 tissue-based prognostic gene signatures from 7 publicly available HCC transcriptomic studies. After bioinformatics analysis and comparison, the HCC CTC-derived gene signatures showed high concordance with HCC tissue-derived gene signatures from TCGA database, suggesting that HCC CTCs purified by Click Chips could enable the translation of HCC tissue molecular profiling into a noninvasive setting.
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- 2021
15. Lenvatinib plus pembrolizumab versus lenvatinib plus placebo for advanced hepatocellular carcinoma (LEAP-002): a randomised, double-blind, phase 3 trial
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Strasser, Simone, Thompson, Alexander, Roohullah, Aflah, Sievert, William, Andelkovic, Vladimir, Knox, Jennifer, Davies, Janine, Asselah, Jamil, Brahmania, Mayur, Majeed, Habeeb, Villanueva, Luis, Yanez Weber, Patricio, Garrido, Marcelo, Pizarro, Gonzalo Ignacio, Yanez, Nicolas, Xu, Ruocai, Ou, Shuangyan, Ren, Zhenggang, Pan, Hongming, Meng, Zhiqiang, Gu, Kangsheng, Chen, Xi, Zhang, Tao, Hao, Chunyi, Cao, Peiguo, Guo, Yabing, Qin, Shukui, Xiao, Juxiang, Fang, Weijia, Wang, Xin, Bai, Yuxian, Chen, Xiaoming, Yan, Dong, Zhao, Hong, Ying, Jieer, Bonilla, Carlos, Urrego, Olga, Zambrano, Angela, Lema, Mauricio, Restrepo Gutierrez, Juan Carlos, Cardona, Andres, Franco Millan, Sandra, Oscar, Madiedo, Ramos, Victor, Merle, Philippe, LeSourd, Samuel, Edeline, Julien, Bronowicki, Jean-Pierre, Bourliere, Marc, Cattan, Stephane, Bouattour, Mohamed, Mineur, Laurent, Regnault, Helene, Dauvois, Barbara, Schulze, Kornelius, Folprecht, Gunnar, Geier, Andreas, Waidmann, Oliver, Finkelmeier, Fabian, Venerito, Marino, Berres, Marie-Luise, Berg, Thomas, Lange, Christian, Schmidt, Hartmut, Waldschmidt, Dirk T, Bitzer, Michael, McDermott, Ray, Duffy, Austin, Masi, Gianluca, Zagonel, Vittorina, Tonini, Giuseppe, Piscaglia, Fabio, Gori, Stefania, Rizzo, Mimma, Biscaldi, Elisa, Foltran, Luisa, Cabibbo, Giuseppe, Ikeda, Masafumi, Kudo, Masatoshi, Aikata, Hiroshi, Numata, Kazushi, Marusawa, Hiroyuki, Kato, Naoya, Kurosaki, Masayuki, Morimoto, Manabu, Yamashita, Tatsuya, Koga, Hironori, Masaki, Tsutomu, Tateishi, Ryosuke, Inaba, Yoshitaka, Arakawa, Tomohiro, Suzuki, Yoshiyuki, Akua, Norio, Kobayashi, Masahiro, Hosaka, Tetsuya, Nakamuta, Makoto, Oza, Noriko, Kondo, Shunsuke, Furuse, Junji, Nagashima, Fumio, Kitano, Masayuki, Takaguchi, Koichi, Ryoo, Baek-Yeol, Lim, Ho Yeong, Kim, Jee Hyun, Kim, Tae-You, Kim, Han Sang, Hernandez Hernandez, Carlos, Motola Kuba, Daniel, Segura Gonzalez, Manuel, Cabrera Luviano, Jesus, Huitzil Melendez, Fidel, Ramirez Godinez, Francisco, Silva-Bravo, Fernando, Gane, Edward, Stedman, Catherine, Kwiatkowski, Mariusz, Wyrwicz, Lucjan, Nowakowska-Zajdel, Ewa, Kraj, Leszek, Janczewska, Ewa, Surma-Wlodarczyk, Renata, Breder, Valeriy, Sekacheva, Marina, Orlova, Rashida, Vasilyev, Alexander, Zukov, Ruslan, Vladimirov, Vladimir, Minguez, Beatriz, Matilla Pena, Ana, Fernandez Castroagudin, Javier, Romero Gomez, Manuel, Luis Lledo, Jose, Rubin, Angel, Garcia Sanchez, Araceli, Calleja Panero, Jose, Yu, Ming-Chin, Shen, Ying-Chun, Huang, Yi-Hsiang, Jeng, Long-Bin, Chang, Ting-Tsung, Yang, Sheng-Shun, Chen, Shinn-Cherng, Dechaphunkul, Arunee, Tanwandee, Tawesak, Leerapun, Apinya, Seker, Mesut, Harputluoglu, Hakan, Cicin, Irfan, Oksuzoglu, Berna, Bilici, Mehmet, Sezgin Goksu, Sema, Artac, Mehmet, Cil, Timucin, Yalcin, Suayib, Meyer, Tim, Sarker, Debashis, Rao, Ankit, Palmer, Daniel, Evans, Jeff, Hubner, Richard, Finn, Richard, Ulahannan, Susanna, Zakari, Ahmed, Feun, Lynn, Al-Rajabi, Raed, Sung, Max, He, Aiwu, Kardosh, Adel, Goyal, Lipika, Li, Daneng, Choi, Minsig, Posada, Juan, Dodlapati, Jyothi, Shroff, Rachna, Agrawal, Saurabh, Gopaluni, Srivalli, Akce, Mehmet, Alese, Olatunji, Baron, Ari, Dunne, Richard, Loaiza-Bonilla, Arturo, Frenette, Catherine, Llovet, Josep M, Kumada, Hiromitsu, Cheng, Ann-Lii, Galle, Peter R, Kaneko, Shuichi, Wang, Anran, Mody, Kalgi, Dutcus, Corina, Dubrovsky, Leonid, Siegel, Abby B, and Finn, Richard S
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- 2023
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16. Effectiveness and safety of atezolizumab-bevacizumab in patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis
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Kulkarni, Anand V., Tevethia, Harshvardhan, Kumar, Karan, Premkumar, Madhumita, Muttaiah, Mark D., Hiraoka, Atsushi, Hatanaka, Takeshi, Tada, Toshifumi, Kumada, Takashi, Kakizaki, Satoru, Vogel, Arndt, Finn, Richard S., Rao, Padaki Nagaraja, Pillai, Anjana, Reddy, Duvvur Nageshwar, and Singal, Amit G.
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- 2023
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17. Combination immunotherapy for hepatocellular carcinoma
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Rimassa, Lorenza, Finn, Richard S., and Sangro, Bruno
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- 2023
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18. Hepatocellular Carcinoma–Circulating Tumor Cells Expressing PD‐L1 Are Prognostic and Potentially Associated With Response to Checkpoint Inhibitors
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Winograd, Paul, Hou, Shuang, Court, Colin M, Lee, Yi‐Te, Chen, Pin‐Jung, Zhu, Yazhen, Sadeghi, Saeed, Finn, Richard S, Teng, Pai‐Chi, Wang, Jasmin J, Zhang, Zhicheng, Liu, Hongtao, Busuttil, Ronald W, Tomlinson, James S, Tseng, Hsian‐Rong, and Agopian, Vatche G
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Liver Cancer ,Liver Disease ,Digestive Diseases ,Clinical Research ,Cancer ,Rare Diseases ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,4.1 Discovery and preclinical testing of markers and technologies ,Good Health and Well Being ,Clinical sciences - Abstract
Hepatocellular carcinoma (HCC) is a leading cause of mortality. Checkpoint inhibitors of programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown great efficacy, but lack biomarkers that predict response. Circulating tumor cells (CTCs) have promise as a liquid-biopsy biomarker; however, data on HCC CTCs expressing PD-L1 have not been reported. We sought to detect PD-L1-expressing HCC-CTCs and investigated their role as a prognostic and predictive biomarker. Using an antibody-based platform, CTCs were enumerated/phenotyped from a prospective cohort of 87 patients with HCC (49 early-stage, 22 locally advanced, and 16 metastatic), 7 patients with cirrhosis, and 8 healthy controls. Immunocytochemistry identified total HCC CTCs (4',6-diamidino-2-phenylindole-positive [DAPI+]/cytokeratin-positive [CK+]/clusters of differentiation 45-negative [CD45-]) and a subpopulation expressing PD-L1 (DAPI+/CK+/PD-L1+/CD45-). PD-L1+ CTCs were identified in 4 of 49 (8.2%) early-stage patients, but 12 of 22 (54.5%) locally advanced and 15 of 16 (93.8%) metastatic patients, accurately discriminating early from locally advanced/metastatic HCC (sensitivity = 71.1%, specificity = 91.8%, area under the receiver operating characteristic curve = 0.807; P
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- 2020
19. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial
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Akce, Mehmet, Ales Diaz, Inmaculada, Alves, Gustavo, Anand, Sumitra, Arslan, Cagatay, Asselah, Jamil, Assenat, Eric, Aubin, Francine, Bai, Li-Yuan, Bai, Yuxian, Barajas, Olga, Bates, Susan, Begbie, Stephen, Ben-Aharon, Irit, Beri, Nina, Berres, Marie-Luise, Blanc, Jean-Frederic, Borbath, Ivan, Bordonaro, Robert, Bouattour, Mohamed, Brandi, Giovanni, Burgoyne, Adam, Butthongkomvong, Kritiya, Camandaroba, Marcos, Cao, Ke, Carballido, Marcela, Chan, Stephan Lam, Chen, Jen-Shi, Chen, Ming-Huang, Chen, Xiaoming, Cheng, Ashley, Chiu, Tai-Jan, Choi, Hye Jin, Chon, Hong Jae, Collignon, Joelle, Cubillo Gracian, Antonio, Davis, Sarah, de Carvalho, Ricardo Saraiva, de Groot, D.J.A., Demols, Anne, De Vos, Judith, Diab, Maria, Easaw, Jacob, Eatock, Martin, Edeline, Julien, Elias, Rawad, Eskens, Fredericus, Falcone, Alfredo, Fernandez, Plinio, Finn, Richard, Franke, Fabio, Furukawa, Masayuki, Furuse, Junji, Gbolahan, Olumide, Geboes, Karen, Geneser, Keri-Lee, Geng, Zhimin, Geva, Ravit, Gillmore, Roopinder, Goetze, Thorsten, Gou, Hongfeng, Grasselli, Julieta, Gu, Shanzhi, Gumus, Mahmut, Haj Mohammad, Nadia, Hao, Chunyi, Harputluoglu, Hakan, Hatoum, Hassan, Heinemann, Volker, Ho, Wang Kwong, Hsu, Chiun, Hubert, Ayala, Hwang, Juneul, Inanc, Mevlude, Iseas, Soledad, Jeyasingam, Vaishnavi, Jimenez Fonseca, Paula, Joubert, Warren, Juengsamarn, Jitlada, Kaen, Diego, Kanai, Masashi, Kasper-Virchow, Stefan, Kazemi, Ghazaleh, Kelleher, Fergal, Kelley, Robin, Kim, Jin Won, Kim, Jong Gwang, Kinupe Abrahao, Ana Beatriz, Klumpen, Heinz, Kochenderfer, Mark, Kose, Fatih, Lam, Ho Ching, Lee, Choong-kun, Lee, Hyun Woo, Lee, Margaret, Lee, Myung Ah, Lee, Wai Man Sarah, Le Sourd, Samuel, Li, Dongliang, Li, Wei, Liang, Houjie, Liang, Tingbo, Lim, Chun Sen, Lingerfelt, Brian, Lopez, Charles, Low, John, Macarulla Mercade, Teresa, Malka, David, Mao, Yimin, Masi, Gianluca, McCune, Steven, McDermott, Ray, McWhirter, Elaine, Mendez, Guillermo, Milella, Michele, Mizuno, Nobumasa, Mizutani, Tomonori, Moniz, Camila, Morales, Luisa, Munoz Martin, Andres Jesús, Nervi, Bruno, Ngamphaiboon, Nuttapong, Oh, Sang Cheul, Oksuzoglu, Berna, Outlaw, Darryl, Ozaka, Masato, Ozguroglu, Mustafa, Ozyilkan, Ozgur, Painemal, Claudio, Pan, Yueyin, Park, Joon Oh, Pelzer, Uwe, Peng, Chuang, Petorin, Caroline, Pezet, Denis, Power, Derek, Qin, Shukui, Ren, Zhenggang, Roohullah, Aflah, Ryu, Hyewon, Salman, Pamela, Sasaki, Mitsuhito, Sasidharan, Rita, Satoh, Taroh, Schulze, Kornelius, Scott-Brown, Martin, Segovia, Ruben, Seufferlein, Thomas, Siena, Salvatore, Sinapi, Isabelle, Smolenschi, Cristina, Song, Tianqiang, Sookprasert, Aumkhae, Soparattanapaisarn, Nopadol, Starling, Naureen, Stein, Stacey, Stemmer, Salomon, Su, Haichuan, Sugimoto, Rie, Suksombooncharoen, Thatthan, Tam, Vincent, Tan, Ai Lian, Tan, Chih Kiang, Tanasanvimon, Suebpong, Tonini, Giuseppe, Tortora, Giampaolo, Tsuji, Akihito, Ueno, Makoto, Uribe, Rodrigo, Venerito, Marino, Verdaguer Mata, Helena, Verslype, Chris, Victorino, Ana Paula, Vogel, Arndt, Wade, James, Waldschmidt, Dirk Thomas, Wang, Lu, Wan Isahk, Wan Zamaniah, Wasan, Harpeet, Weschenfelder, Rui, Wong, Chun Yin, Wong, Yoke Fui, Yalcin, Suayib, Yanez Weber, Patricio, Yang, Xuezhong, Yasui, Hisateru, Yau, Thomas, Yazici, Ozan, Yen, Chia-Jui, Ying, Jieer, Yoo, Changhoon, Yu, Wenchang, Zhao, Haitao, Kelley, Robin Kate, Finn, Richard S, Klümpen, Heinz-Josef, Chan, Stephen L, Valle, Juan W, Yu, Li, Malhotra, Usha, and Siegel, Abby B
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- 2023
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20. Purification of HCC-specific extracellular vesicles on nanosubstrates for early HCC detection by digital scoring.
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Sun, Na, Lee, Yi-Te, Zhang, Ryan Y, Kao, Rueihung, Teng, Pai-Chi, Yang, Yingying, Yang, Peng, Wang, Jasmine J, Smalley, Matthew, Chen, Pin-Jung, Kim, Minhyung, Chou, Shih-Jie, Bao, Lirong, Wang, Jing, Zhang, Xinyue, Qi, Dongping, Palomique, Juvelyn, Nissen, Nicolas, Han, Steven-Huy B, Sadeghi, Saeed, Finn, Richard S, Saab, Sammy, Busuttil, Ronald W, Markovic, Daniela, Elashoff, David, Yu, Hsiao-Hua, Li, Huiying, Heaney, Anthony P, Posadas, Edwin, You, Sungyong, Yang, Ju Dong, Pei, Renjun, Agopian, Vatche G, Tseng, Hsian-Rong, and Zhu, Yazhen
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Humans ,Carcinoma ,Hepatocellular ,Liver Neoplasms ,Liver Cirrhosis ,Disease Progression ,Dimethylpolysiloxanes ,RNA ,Messenger ,Diagnosis ,Differential ,Neoplasm Staging ,Microfluidic Analytical Techniques ,Case-Control Studies ,ROC Curve ,Reverse Transcriptase Polymerase Chain Reaction ,Nanostructures ,Computer Simulation ,Aged ,Middle Aged ,Female ,Male ,Nanowires ,Early Detection of Cancer ,Lab-On-A-Chip Devices ,Hep G2 Cells ,Click Chemistry ,Extracellular Vesicles ,Biomarkers ,Tumor ,Liquid Biopsy ,Computational Chemistry - Abstract
We report a covalent chemistry-based hepatocellular carcinoma (HCC)-specific extracellular vesicle (EV) purification system for early detection of HCC by performing digital scoring on the purified EVs. Earlier detection of HCC creates more opportunities for curative therapeutic interventions. EVs are present in circulation at relatively early stages of disease, providing potential opportunities for HCC early detection. We develop an HCC EV purification system (i.e., EV Click Chips) by synergistically integrating covalent chemistry-mediated EV capture/release, multimarker antibody cocktails, nanostructured substrates, and microfluidic chaotic mixers. We then explore the translational potential of EV Click Chips using 158 plasma samples of HCC patients and control cohorts. The purified HCC EVs are subjected to reverse-transcription droplet digital PCR for quantification of 10 HCC-specific mRNA markers and computation of digital scoring. The HCC EV-derived molecular signatures exhibit great potential for noninvasive early detection of HCC from at-risk cirrhotic patients with an area under receiver operator characteristic curve of 0.93 (95% CI, 0.86 to 1.00; sensitivity = 94.4%, specificity = 88.5%).
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- 2020
21. Somatic copy number profiling from hepatocellular carcinoma circulating tumor cells.
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Court, Colin M, Hou, Shuang, Liu, Lian, Winograd, Paul, DiPardo, Benjamin J, Liu, Sean X, Chen, Pin-Jung, Zhu, Yazhen, Smalley, Matthew, Zhang, Ryan, Sadeghi, Saeed, Finn, Richard S, Kaldas, Fady M, Busuttil, Ronald W, Zhou, Xianghong J, Tseng, Hsian-Rong, Tomlinson, James S, Graeber, Thomas G, and Agopian, Vatche G
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Molecular medicine ,Prognostic markers - Abstract
Somatic copy number alterations (SCNAs) are important genetic drivers of many cancers. We investigated the feasibility of obtaining SCNA profiles from circulating tumor cells (CTCs) as a molecular liquid biopsy for hepatocellular carcinoma (HCC). CTCs from ten HCC patients underwent SCNA profiling. The Cancer Genome Atlas (TCGA) SCNA data were used to develop a cancer origin classification model, which was then evaluated for classifying 44 CTCs from multiple cancer types. Sequencing of 18 CTC samples (median: 4 CTCs/sample) from 10 HCC patients using a low-resolution whole-genome sequencing strategy (median: 0.88 million reads/sample) revealed frequent SCNAs in previously reported HCC regions such as 8q amplifications and 17p deletions. SCNA profiling revealed that CTCs share a median of 80% concordance with the primary tumor. CTCs had SCNAs not seen in the primary tumor, some with prognostic implications. Using a SCNA profiling model, the tissue of origin was correctly identified for 32/44 (73%) CTCs from 12/16 (75%) patients with different cancer types.
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- 2020
22. Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial.
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Diéras, Véronique, Harbeck, Nadia, Joy, Anil Abraham, Gelmon, Karen, Ettl, Johannes, Verma, Sunil, Lu, Dongrui R, Gauthier, Eric, Schnell, Patrick, Mori, Ave, Rugo, Hope S, and Finn, Richard S
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Humans ,Breast Neoplasms ,Piperazines ,Pyridines ,Receptor ,erbB-2 ,Antineoplastic Combined Chemotherapy Protocols ,Postmenopause ,Female ,Letrozole ,Breast cancer ,Hematologic ,Neutropenia ,Palbociclib ,Safety ,Receptor ,ErbB-2 ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundPALOMA-2 confirmed that first-line palbociclib + letrozole improved progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.46-0.72) in postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). This analysis evaluated palbociclib-associated hematologic adverse events (AEs) and provides insight on managing these AEs.Materials and methodsPostmenopausal women with ER+/HER2- ABC were randomly assigned 2:1 to letrozole (2.5 mg daily continuously) plus oral palbociclib (125 mg daily; 3 weeks on/1 week off) or placebo. Safety assessments were performed at baseline, days 1 and 15 (first two cycles) and day 1 of subsequent cycles, and included white blood cell, platelet, and absolute neutrophil count (ANC).ResultsPALOMA-2 randomized 666 women to palbociclib + letrozole (n = 444) or placebo + letrozole (n = 222). Neutropenia was the most common AE (95.3%) with palbociclib (grade 3, 55.6%; grade 4, 11.5%) and was managed by dose modifications; progression-free survival was similar between patients who experienced grade ≥ 3 neutropenia versus those who did not. Median (range) time to onset of neutropenia with palbociclib + letrozole was 15 (12-700) days (grade ≥ 3, 28.0 [12-854] days); median duration of each neutropenia episode grade ≥ 3 was 7.0 days. Asian ethnicity and low baseline ANC were associated with increased risk of grade 3/4 neutropenia with palbociclib (p < .001).ConclusionPalbociclib + letrozole was generally well tolerated. Neutropenia, the most frequently reported AE in women with ER+/HER2- ABC, was mostly transient and manageable by dose modifications in patients who experienced grade ≥ 3 neutropenia, without appearing to compromise efficacy. (Pfizer; NCT01740427) IMPLICATIONS FOR PRACTICE: Palbociclib demonstrated an acceptable safety profile in PALOMA-2 in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) receiving first-line palbociclib + letrozole. Although hematologic adverse events (AEs) are typically expected with anticancer therapies and are often clinically significant, palbociclib-related hematologic AEs, particularly neutropenia (most frequent AE), were transient/manageable by dose reduction, interruption, or cycle delay, which is in contrast to the more profound neutropenia associated with chemotherapy. Palbociclib dose adjustments decreased hematologic AE severity without appearing to compromise efficacy, supporting palbociclib + letrozole as a first-line treatment for ER+/HER2- ABC.
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- 2019
23. Molecular Markers of Response to Anti-PD1 Therapy in Advanced Hepatocellular Carcinoma
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Haber, Philipp K., Castet, Florian, Torres-Martin, Miguel, Andreu-Oller, Carmen, Puigvehí, Marc, Miho, Maeda, Radu, Pompilia, Dufour, Jean-Francois, Verslype, Chris, Zimpel, Carolin, Marquardt, Jens U., Galle, Peter R., Vogel, Arndt, Bathon, Melanie, Meyer, Tim, Labgaa, Ismail, Digklia, Antonia, Roberts, Lewis R., Mohamed Ali, Mohamed A., Mínguez, Beatriz, Citterio, Davide, Mazzaferro, Vincenzo, Finkelmeier, Fabian, Trojan, Jörg, Özdirik, Burcin, Müller, Tobias, Schmelzle, Moritz, Bejjani, Anthony, Sung, Max W., Schwartz, Myron E., Finn, Richard S., Thung, Swan, Villanueva, Augusto, Sia, Daniela, and Llovet, Josep M.
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- 2023
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24. Overall survival and objective response in advanced unresectable hepatocellular carcinoma: A subanalysis of the REFLECT study
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Kudo, Masatoshi, Finn, Richard S., Qin, Shukui, Han, Kwang-Hyub, Ikeda, Kenji, Cheng, Ann-Lii, Vogel, Arndt, Tovoli, Francesco, Ueshima, Kazuomi, Aikata, Hiroshi, López, Carlos López, Pracht, Marc, Meng, Zhiqiang, Daniele, Bruno, Park, Joong-Won, Palmer, Daniel, Tamai, Toshiyuki, Saito, Kenichi, Dutcus, Corina E., and Lencioni, Riccardo
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- 2023
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25. Molecular correlates of clinical response and resistance to atezolizumab in combination with bevacizumab in advanced hepatocellular carcinoma
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Zhu, Andrew X., Abbas, Alexander R., de Galarreta, Marina Ruiz, Guan, Yinghui, Lu, Shan, Koeppen, Hartmut, Zhang, Wenjun, Hsu, Chih-Hung, He, Aiwu Ruth, Ryoo, Baek-Yeol, Yau, Thomas, Kaseb, Ahmed O., Burgoyne, Adam M., Dayyani, Farshid, Spahn, Jessica, Verret, Wendy, Finn, Richard S., Toh, Han Chong, Lujambio, Amaia, and Wang, Yulei
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- 2022
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26. Combination and Optimal Sequencing of Systemic and Locoregional Therapies in Hepatocellular Carcinoma: Proceedings from the Society of Interventional Radiology Foundation Research Consensus Panel
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Thornton, Lindsay M., primary, Abi-Jaoudeh, Nadine, additional, Lim, Howard J., additional, Malagari, Katerina, additional, Spieler, Benjamin Oren, additional, Kudo, Masatoshi, additional, Finn, Richard S., additional, Lencioni, Riccardo, additional, White, Sarah B., additional, Kokabi, Nima, additional, Jeyarajah, D. Rohan, additional, Chaudhury, Prosanto, additional, and Liu, David, additional
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- 2024
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27. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update Clinical Insights
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Rose, Michal G., primary, Kennedy, Erin B., additional, Abou-Alfa, Ghassan K., additional, Finn, Richard S., additional, Gade, Terence, additional, Kelley, R. Kate, additional, Taddei, Tamar, additional, and Gordan, John D., additional
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- 2024
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28. Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment
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Llovet, Josep M., Vogel, Arndt, Madoff, David C., Finn, Richard S., Ogasawara, Sadahisa, Ren, Zhenggang, Mody, Kalgi, Li, Jerry J., Siegel, Abby B., Dubrovsky, Leonid, and Kudo, Masatoshi
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- 2022
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29. Recent Developments and Therapeutic Strategies against Hepatocellular Carcinoma
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Yarchoan, Mark, Agarwal, Parul, Villanueva, Augusto, Rao, Shuyun, Dawson, Laura A, Karasic, Thomas, Llovet, Josep M, Finn, Richard S, Groopman, John D, El-Serag, Hashem B, Monga, Satdarshan P, Wang, Xin Wei, Karin, Michael, Schwartz, Robert E, Tanabe, Kenneth K, Roberts, Lewis R, Gunaratne, Preethi H, Tsung, Allan, Brown, Kimberly A, Lawrence, Theodore S, Salem, Riad, Singal, Amit G, Kim, Amy K, Rabiee, Atoosa, Resar, Linda, Meyer, Jeffrey, Hoshida, Yujin, He, Aiwu Ruth, Ghoshal, Kalpana, Ryan, Patrick B, Jaffee, Elizabeth M, Guha, Chandan, Mishra, Lopa, Coleman, C Norman, and Ahmed, Mansoor M
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Liver Disease ,Liver Cancer ,Cancer ,Orphan Drug ,Rare Diseases ,Chronic Liver Disease and Cirrhosis ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Anilides ,Antibodies ,Monoclonal ,Humanized ,Carcinoma ,Hepatocellular ,Chemoembolization ,Therapeutic ,Clinical Trials as Topic ,Humans ,Immunotherapy ,Liver Neoplasms ,Molecular Targeted Therapy ,Mutation ,Phenylurea Compounds ,Protein Kinase Inhibitors ,Pyridines ,Quinolines ,beta Catenin ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.
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- 2019
30. Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer
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Diéras, Véronique, Rugo, Hope S, Schnell, Patrick, Gelmon, Karen, Cristofanilli, Massimo, Loi, Sherene, Colleoni, Marco, Lu, Dongrui R, Mori, Ave, Gauthier, Eric, Bartlett, Cynthia Huang, Slamon, Dennis J, Turner, Nicholas C, and Finn, Richard S
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Clinical Research ,Breast Cancer ,Clinical Trials and Supportive Activities ,Cancer ,Patient Safety ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Combined Chemotherapy Protocols ,Breast Neoplasms ,Double-Blind Method ,Female ,Follow-Up Studies ,Fulvestrant ,Humans ,Letrozole ,Middle Aged ,Piperazines ,Prognosis ,Pyridines ,Receptor ,ErbB-2 ,Receptors ,Estrogen ,Receptor ,erbB-2 ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundPalbociclib administered with endocrine therapy was tolerable when the overall incidence of toxicities was assessed separately for three PALOMA studies. This study analyzed pooled, longer-term PALOMA safety data longitudinally.MethodsData were pooled from three randomized phase II and III studies (ClinicalTrials.gov: NCT00721409, NCT01740427, NCT01942135) of hormone receptor-positive/human epidermal growth factor receptor 2‒negative advanced breast cancer patients. Front-line patients were randomly assigned to receive letrozole with/without palbociclib (PALOMA-1) or letrozole plus palbociclib/placebo (PALOMA-2). In PALOMA-3, patients with prior endocrine resistance received fulvestrant plus palbociclib/placebo. The cumulative event rates of adverse events (AEs), reporting up to 50 months of treatment, were assessed over time.ResultsPatients who received endocrine therapy (n = 1343) were included in this pooled analysis (872 were also treated with palbociclib, and 471 were not). The most common AEs with palbociclib plus endocrine therapy were neutropenia and infections (any grade, 80.6% and 54.7%, respectively), which were higher than in the endocrine monotherapy arm (any grade, 5.3% and 36.9%). The most common hematologic AEs (≥15.0% in the palbociclib arm) were more likely to be reported in the initial months of the study, after which time the cumulative event rate did not substantially increase. With palbociclib plus endocrine therapy, any grade AEs leading to permanent discontinuation over three years occurred in only 8.3% of patients.ConclusionsBased on these long-term safety analyses, there is no evidence of specific cumulative or delayed toxicities with palbociclib plus endocrine therapy, supporting the ongoing investigation of palbociclib plus endocrine therapy in early breast cancer (NCT02513394).
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- 2019
31. Immunotherapies for hepatocellular carcinoma
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Llovet, Josep M., Castet, Florian, Heikenwalder, Mathias, Maini, Mala K., Mazzaferro, Vincenzo, Pinato, David J., Pikarsky, Eli, Zhu, Andrew X., and Finn, Richard S.
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- 2022
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32. Comparative biomarker analysis of PALOMA-2/3 trials for palbociclib
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Zhu, Zhou, Turner, Nicholas C., Loi, Sherene, André, Fabrice, Martin, Miguel, Diéras, Véronique, Gelmon, Karen A., Harbeck, Nadia, Zhang, Cathy, Cao, Joan Q., Yan, Zhengming, Lu, Dongrui R., Wei, Ping, VanArsdale, Todd L., Rejto, Paul A., Huang, Xin, Rugo, Hope S., Loibl, Sibylle, Cristofanilli, Massimo, Finn, Richard S., and Liu, Yuan
- Published
- 2022
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33. A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors
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Chan, Stephen L., Schuler, Martin, Kang, Yoon-Koo, Yen, Chia-Jui, Edeline, Julien, Choo, Su Pin, Lin, Chia-Chi, Okusaka, Takuji, Weiss, Karl-Heinz, Macarulla, Teresa, Cattan, Stéphane, Blanc, Jean-Frederic, Lee, Kyung-Hun, Maur, Michela, Pant, Shubham, Kudo, Masatoshi, Assenat, Eric, Zhu, Andrew X., Yau, Thomas, Lim, Ho Yeong, Bruix, Jordi, Geier, Andreas, Guillén-Ponce, Carmen, Fasolo, Angelica, Finn, Richard S., Fan, Jia, Vogel, Arndt, Qin, Shukui, Riester, Markus, Katsanou, Vasiliki, Chaudhari, Monica, Kakizume, Tomoyuki, Gu, Yi, Porta, Diana Graus, Myers, Andrea, and Delord, Jean-Pierre
- Published
- 2022
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34. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial
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Yau, Thomas, Park, Joong-Won, Finn, Richard S, Cheng, Ann-Lii, Mathurin, Philippe, Edeline, Julien, Kudo, Masatoshi, Harding, James J, Merle, Philippe, Rosmorduc, Olivier, Wyrwicz, Lucjan, Schott, Eckart, Choo, Su Pin, Kelley, Robin Kate, Sieghart, Wolfgang, Assenat, Eric, Zaucha, Renata, Furuse, Junji, Abou-Alfa, Ghassan K, El-Khoueiry, Anthony B, Melero, Ignacio, Begic, Damir, Chen, Gong, Neely, Jaclyn, Wisniewski, Tami, Tschaika, Marina, and Sangro, Bruno
- Published
- 2022
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35. Impact of Bevacizumab Being Skipped due to Adverse Events of Special Interest for Bevacizumab in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab plus Bevacizumab: An Exploratory Analysis of the Phase III IMbrave150 Study.
- Author
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Kudo, Masatoshi, Tsuchiya, Kaoru, Shao, Yu-Yun, Finn, Richard S., Galle, Peter R., Ducreux, Michel, Cheng, Ann-Lii, Yamashita, Tatsuya, Koga, Hironori, Take, Ryosuke, Yamada, Kyoko, Asakawa, Takashi, Nakagawa, Yuki, and Ikeda, Masafumi
- Subjects
HEPATOCELLULAR carcinoma ,OVERALL survival ,PROGRESSION-free survival ,BEVACIZUMAB ,SPECIAL events - Abstract
Introduction: The phase III IMbrave150 study established atezolizumab + bevacizumab as the global standard of care in patients with unresectable hepatocellular carcinoma (HCC). This exploratory analysis examined the impact of bevacizumab interruption due to bevacizumab adverse events of special interest (AESIs). Methods: Patients in IMbrave150 who were randomized to atezolizumab + bevacizumab and received treatment for ≥6 months (to reduce immortal time bias) were included in group A-1 if bevacizumab had ever been skipped due to bevacizumab AESIs or to group A-2 otherwise. Efficacy analyses included overall survival (OS) and progression-free survival (PFS) by whether bevacizumab was skipped (group A-1 vs. A-2). PFS was evaluated per independent review facility (IRF)-assessed Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and HCC-modified RECIST (IRF-HCC mRECIST). Safety was also evaluated. Results: Of the 210 patients who received ≥6 months of atezolizumab + bevacizumab, 69 were assigned to group A-1 and 141 to A-2. At data cutoff (August 20, 2020), hazard ratio (HR) for OS was 1.04 (95% CI: 0.64, 1.69) for group A-1 versus A-2. HR for PFS was 1.07 (95% CI: 0.74, 1.55) per IRF-assessed RECIST 1.1 and 1.10 (95% CI: 0.76, 1.59; 15.5 vs. 9.7 months) per IRF-HCC mRECIST for group A-1 versus A-2. Safety profiles for atezolizumab and bevacizumab were largely similar between groups. More group A-1 patients had grade 3/4 adverse events. A separate analysis investigating the impact of immortal time bias in patients who received ≥3 months of atezolizumab + bevacizumab supported the appropriateness of the ≥6-month landmark analysis. Discussion/Conclusion: Efficacy was similar between patients who skipped bevacizumab due to bevacizumab AESIs and those who did not. Although this comparison was nonrandomized and exploratory, results suggest that skipping bevacizumab due to bevacizumab AESIs did not considerably impact the efficacy and safety of atezolizumab + bevacizumab. [ABSTRACT FROM AUTHOR]
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- 2024
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36. A Phase 1b Study of Lenvatinib plus Pembrolizumab in Patients with Unresectable Hepatocellular Carcinoma: Extended Analysis of Study 116.
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Kudo, Masatoshi, Finn, Richard S., Ikeda, Masafumi, Sung, Max W., Baron, Ari D., Okusaka, Takuji, Kobayashi, Masahiro, Kumada, Hiromitsu, Kaneko, Shuichi, Pracht, Marc, Meyer, Tim, Nagao, Satoshi, Saito, Kenichi, Mody, Kalgi, Ramji, Zahra, Dubrovsky, Leonid, and Llovet, Josep M.
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PROGRESSION-free survival ,OVERALL survival ,HEPATOCELLULAR carcinoma ,PATIENT safety ,ANTINEOPLASTIC agents - 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. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases
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Marrero, Jorge A, Kulik, Laura M, Sirlin, Claude B, Zhu, Andrew X, Finn, Richard S, Abecassis, Michael M, Roberts, Lewis R, and Heimbach, Julie K
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Good Health and Well Being ,Antineoplastic Agents ,Carcinoma ,Hepatocellular ,Early Detection of Cancer ,Female ,Hepatectomy ,Humans ,Liver ,Liver Neoplasms ,Liver Transplantation ,Male ,Neoplasm Staging ,United States ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Published
- 2018
38. A novel multimarker assay for the phenotypic profiling of circulating tumor cells in hepatocellular carcinoma
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Court, Colin M, Hou, Shuang, Winograd, Paul, Segel, Nicholas H, Li, Qingyu Wilda, Zhu, Yazhen, Sadeghi, Saeed, Finn, Richard S, Ganapathy, Ekambaram, Song, Min, French, Samuel W, Naini, Bita V, Sho, Shonan, Kaldas, Fady M, Busuttil, Ronald W, Tomlinson, James S, Tseng, Hsian‐Rong, and Agopian, Vatche G
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Clinical Research ,Digestive Diseases ,Cancer ,Rare Diseases ,Liver Disease ,Liver Cancer ,Good Health and Well Being ,Aged ,Asialoglycoprotein Receptor ,Biological Assay ,Biomarkers ,Tumor ,Carcinoma ,Hepatocellular ,Cell Line ,Tumor ,Epithelial Cell Adhesion Molecule ,Female ,Glypicans ,Healthy Volunteers ,Humans ,Immunoassay ,Kaplan-Meier Estimate ,Liquid Biopsy ,Liver Cirrhosis ,Liver Neoplasms ,Male ,Microfluidics ,Middle Aged ,Neoplasm Recurrence ,Local ,Neoplastic Cells ,Circulating ,Prognosis ,Prospective Studies ,Sensitivity and Specificity ,Tissue Array Analysis ,Vimentin ,Clinical Sciences ,Surgery ,Clinical sciences - Abstract
Current clinicopathologic staging systems and serum biomarkers poorly discriminate tumor biology in hepatocellular carcinoma (HCC), with high recurrence rates following curative-intent surgical resection and liver transplantation (LT). Identification of accurate biomarkers for improved prognostication and treatment selection is a critical unmet need. We sought to develop a novel "liquid-biopsy" assay capable of detecting HCC circulating tumor cells (CTCs) and characterizing phenotypic subpopulations with prognostic significance. Using HCC cell lines, a tissue microarray, and human blood samples, an antibody cocktail targeting the cell-surface markers asialoglycoprotein receptor (ASGPR), glypican-3, and epithelial cell adhesion molecule was optimized for HCC CTC capture using the NanoVelcro CTC Assay. The ability of HCC CTCs and vimentin (VIM)-positive CTCs (a subpopulation expressing an epithelial-to-mesenchymal phenotype) to accurately discriminate tumor stage, recurrence, progression, and overall survival (OS) was evaluated in a prospective study of 80 patients. Multimarker capture detected greater numbers of CTCs than any individual antibody alone for both cell line and patient samples (P < 0.001). HCC CTCs were identified in 59/61 (97%) patients, and HCC (median, 6 CTCs) and non-HCC patients (median, 1 CTC; area under the receiver operating characteristic curve [AUROC] = 0.92; P < 0.001; sensitivity = 84.2%; specificity = 88.5%) were accurately discriminated. VIM-positive CTCs accurately discriminated early-stage, LT eligible patients (median, 0 CTCs) from locally advanced/metastatic, LT ineligible patients (median, 6 CTCs; AUROC = 0.89; P = 0.001; sensitivity = 87.1%; specificity = 90.0%), and predicted OS for all patients (hazard ratio [HR], 2.21; P = 0.001), and faster recurrence after curative-intent surgical or locoregional therapy in potentially curable early-stage HCC (HR, 3.14; P = 0.002). In conclusion, we developed a novel multimarker CTC enrichment assay that detects HCC CTCs with high efficiency and accuracy. A phenotypic subpopulation of VIM-positive CTCs appears to signify the presence of aggressive underlying disease and occult metastases and may have important implications for treatment selection. Liver Transplantation 24 946-960 2018 AASLD.
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- 2018
39. Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer
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Durairaj, Chandrasekar, Ruiz-Garcia, Ana, Gauthier, Eric R, Huang, Xin, Lu, Dongrui R, Hoffman, Justin T, Finn, Richard S, Joy, Anil A, Ettl, Johannes, Rugo, Hope S, Zheng, Jenny, Wilner, Keith D, and Wang, Diane D
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Estrogen ,Clinical Research ,Clinical Trials and Supportive Activities ,Breast Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Adult ,Aged ,Aged ,80 and over ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Breast Neoplasms ,Double-Blind Method ,Electrocardiography ,Female ,Heart Rate ,Humans ,Letrozole ,Middle Aged ,Nitriles ,Piperazines ,Pyridines ,Triazoles ,advanced breast cancer ,concentration-QTc modeling ,ECG ,palbociclib ,QT interval ,Medicinal and Biomolecular Chemistry ,Medical Biochemistry and Metabolomics ,Pharmacology and Pharmaceutical Sciences ,Oncology & Carcinogenesis ,Oncology and carcinogenesis ,Pharmacology and pharmaceutical sciences ,Medicinal and biomolecular chemistry - Abstract
The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.
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- 2018
40. Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma
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Javle, Milind, Lowery, Maeve, Shroff, Rachna T, Weiss, Karl Heinz, Springfeld, Christoph, Borad, Mitesh J, Ramanathan, Ramesh K, Goyal, Lipika, Sadeghi, Saeed, Macarulla, Teresa, El-Khoueiry, Anthony, Kelley, Robin Kate, Borbath, Ivan, Choo, Su Pin, Oh, Do-Youn, Philip, Philip A, Chen, Li-Tzong, Reungwetwattana, Thanyanan, Van Cutsem, Eric, Yeh, Kun-Huei, Ciombor, Kristen, Finn, Richard S, Patel, Anuradha, Sen, Suman, Porter, Dale, Isaacs, Randi, Zhu, Andrew X, Abou-Alfa, Ghassan K, and Bekaii-Saab, Tanios
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Orphan Drug ,Rare Diseases ,Clinical Research ,Digestive Diseases ,Cancer ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Administration ,Oral ,Adult ,Aged ,Antineoplastic Agents ,Bile Duct Neoplasms ,Biomarkers ,Tumor ,Cholangiocarcinoma ,Disease Progression ,Drug Administration Schedule ,Gene Amplification ,Gene Fusion ,Genetic Predisposition to Disease ,Humans ,Middle Aged ,Mutation ,Phenotype ,Phenylurea Compounds ,Progression-Free Survival ,Prospective Studies ,Protein Kinase Inhibitors ,Pyrimidines ,Receptor ,Fibroblast Growth Factor ,Type 2 ,Time Factors ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Purpose No standard treatment exists for patients with cholangiocarcinoma for whom first-line gemcitabine-based therapy fails. Fibroblast growth factor receptor 2 ( FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations. Methods A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions or other FGFR alterations whose disease had progressed while receiving prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary end point was investigator-assessed overall response rate. Results Sixty-one patients (35 women; median age, 57 years) with FGFR2 fusion (n = 48), mutation (n = 8), or amplification (n = 3) participated. At the prespecified data cutoff (June 30, 2016), 50 patients had discontinued treatment. All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months). Adverse events included hyperphosphatemia (72.1% all grade), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3 or 4 treatment-related adverse events occurred in 25 patients (41%) and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar-plantar erythrodysesthesia (4.9%). Conclusion BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.
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- 2018
41. AASLD guidelines for the treatment of hepatocellular carcinoma
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Heimbach, Julie K, Kulik, Laura M, Finn, Richard S, Sirlin, Claude B, Abecassis, Michael M, Roberts, Lewis R, Zhu, Andrew X, Murad, M Hassan, and Marrero, Jorge A
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Carcinoma ,Hepatocellular ,Humans ,Liver Neoplasms ,Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology - Published
- 2018
42. Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer
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Slamon, Dennis J., primary, Diéras, Véronique, additional, Rugo, Hope S., additional, Harbeck, Nadia, additional, Im, Seock-Ah, additional, Gelmon, Karen A., additional, Lipatov, Oleg N., additional, Walshe, Janice M., additional, Martin, Miguel, additional, Chavez-MacGregor, Mariana, additional, Bananis, Eustratios, additional, Gauthier, Eric, additional, Lu, Dongrui R., additional, Kim, Sindy, additional, and Finn, Richard S., additional
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- 2024
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43. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline Update
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Gordan, John D., primary, Kennedy, Erin B., additional, Abou-Alfa, Ghassan K., additional, Beal, Eliza, additional, Finn, Richard S., additional, Gade, Terence P., additional, Goff, Laura, additional, Gupta, Shilpi, additional, Guy, Jennifer, additional, Hoang, Hang T., additional, Iyer, Renuka, additional, Jaiyesimi, Ishmael, additional, Jhawer, Minaxi, additional, Karippot, Asha, additional, Kaseb, Ahmed O., additional, Kelley, R. Kate, additional, Kortmansky, Jeremy, additional, Leaf, Andrea, additional, Remak, William M., additional, Sohal, Davendra P.S., additional, Taddei, Tamar H., additional, Wilson Woods, Andrea, additional, Yarchoan, Mark, additional, and Rose, Michal G., additional
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- 2024
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44. Critical Appraisal of Guideline Recommendations on Systemic Therapies for Advanced Hepatocellular Carcinoma
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Cappuyns, Sarah, primary, Corbett, Virginia, additional, Yarchoan, Mark, additional, Finn, Richard S., additional, and Llovet, Josep M., additional
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- 2024
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45. Analysis of patients (pts) with unresectable hepatocellular carcinoma (uHCC) and Child–Pugh (CP)-B liver function treated with regorafenib in routine clinical practice in the observational REFINE study.
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Kim, Yoon Jun, primary, Merle, Philippe, additional, Finn, Richard S., additional, Kudo, Masatoshi, additional, Klümpen, Heinz-Josef, additional, Lim, Ho Yeong, additional, Pinter, Matthias, additional, Babajanyan, Svetlana, additional, Khan, Javeed, additional, Awan, Maria, additional, Özgürdal, Kirhan, additional, and Qin, Shukui, additional
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- 2024
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46. Lenvatinib plus pembrolizumab versus lenvatinib alone as first-line therapy for advanced hepatocellular carcinoma: Longer-term efficacy and safety results from the phase 3 LEAP-002 study.
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Finn, Richard S., primary, Kudo, Masatoshi, additional, Merle, Philippe, additional, Meyer, Tim, additional, Qin, Shukui, additional, Ikeda, Masafumi, additional, Xu, Ruocai, additional, Edeline, Julien, additional, Ryoo, Baek-Yeol, additional, Ren, Zhenggang, additional, Cheng, Ann-Lii, additional, Galle, Peter R., additional, Kaneko, Shuichi, additional, Kumada, Hiromitsu, additional, Wang, Anran, additional, Mody, Kalgi, additional, Dubrovsky, Leonid, additional, Siegel, Abby B., additional, and Llovet, Josep M, additional
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- 2024
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47. 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, Peter, primary, Finn, Richard S, additional, Mitchell, Catherine Ruth, additional, Ndirangu, Kerigo, additional, Ramji, Zahra, additional, Redhead, Gabrielle Sophie, additional, and Pinato, David J, additional
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- 2024
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48. Patient-reported outcomes with atezolizumab plus bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma (IMbrave150): an open-label, randomised, phase 3 trial
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Galle, Peter R, Finn, Richard S, Qin, Shukui, Ikeda, Masafumi, Zhu, Andrew X, Kim, Tae-You, Kudo, Masatoshi, Breder, Valeriy, Merle, Philippe, Kaseb, Ahmed, Li, Daneng, Mulla, Sohail, Verret, Wendy, Xu, Derek-Zhen, Hernandez, Sairy, Ding, Beiying, Liu, Juan, Huang, Chen, Lim, Ho Yeong, Cheng, Ann-Lii, and Ducreux, Michel
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- 2021
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49. Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2
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Kudo, Masatoshi, Galle, Peter R., Brandi, Giovanni, Kang, Yoon-Koo, Yen, Chia-Jui, Finn, Richard S., Llovet, Josep M., Assenat, Eric, Merle, Philippe, Chan, Stephen L., Palmer, Daniel H., Ikeda, Masafumi, Yamashita, Tatsuya, Vogel, Arndt, Huang, Yi-Hsiang, Abada, Paolo B., Yoshikawa, Reigetsu, Shinozaki, Kenta, Wang, Chunxiao, Widau, Ryan C., and Zhu, Andrew X.
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- 2021
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50. A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor
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Bendell, Johanna C, Javle, Milind, Bekaii-Saab, Tanios S, Finn, Richard S, Wainberg, Zev A, Laheru, Daniel A, Weekes, Colin D, Tan, Benjamin R, Khan, Gazala N, Zalupski, Mark M, Infante, Jeffrey R, Jones, Suzanne, Papadopoulos, Kyriakos P, Tolcher, Anthony W, Chavira, Renae E, Christy-Bittel, Janna L, Barrett, Emma, and Patnaik, Amita
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Clinical Research ,Digestive Diseases ,Clinical Trials and Supportive Activities ,Cancer ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Benzimidazoles ,Drug Administration Schedule ,Female ,Humans ,MAP Kinase Kinase 1 ,MAP Kinase Kinase 2 ,Male ,Maximum Tolerated Dose ,Neoplasms ,Proto-Oncogene Proteins B-raf ,Treatment Outcome ,ras Proteins ,binimetinib ,MEK162 ,MEK inhibitor ,gastrointestinal cancers ,colorectal cancers ,clinical trial ,Public Health and Health Services ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundBinimetinib (MEK162; ARRY-438162) is a potent and selective oral MEK 1/2 inhibitor. This phase 1 study determined the maximum tolerated dose (MTD), safety, pharmacokinetic and pharmacodynamic profiles, and preliminary anti-tumour activity of binimetinib in patients with advanced solid tumours, with expansion cohorts of patients with biliary cancer or KRAS- or BRAF-mutant colorectal cancer.MethodsBinimetinib was administered twice daily. Expansion cohorts were enroled after MTD determination following a 3+3 dose-escalation design. Pharmacokinetic properties were determined from plasma samples. Tumour samples were assessed for mutations in RAS, RAF, and other relevant genes. Pharmacodynamic properties were evaluated in serum and skin punch biopsy samples.ResultsNinety-three patients received binimetinib (dose-escalation phase, 19; expansion, 74). The MTD was 60 mg twice daily, with dose-limiting adverse events (AEs) of dermatitis acneiform and chorioretinopathy. The dose for expansion patients was subsequently decreased to 45 mg twice daily because of the frequency of treatment-related ocular toxicity at the MTD. Common AEs across all dose levels included rash (81%), nausea (56%), vomiting (52%), diarrhoea (51%), peripheral oedema (46%), and fatigue (43%); most were grade 1/2. Dose-proportional increases in binimetinib exposure were observed and target inhibition was demonstrated in serum and skin punch biopsy samples. Three patients with biliary cancer had objective responses (one complete and two partial).ConclusionsBinimetinib demonstrated a manageable safety profile, target inhibition, and dose-proportional exposure. The 45 mg twice daily dose was identified as the recommended phase 2 dose. The three objective responses in biliary cancer patients are encouraging and support further evaluation in this population.
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- 2017
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