Article
Oncology
Hao Tang, Longyu Jin, Zhang Zhang, Zhibin Jiang, Zeeshan Malik
Summary: Alectinib is more effective than crizotinib and has lower incidence of adverse reactions in the treatment of ALK-positive non-small cell lung cancer. Meta-analysis results support alectinib as a superior first-line treatment for ALK-positive NSCLC.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yurong Wang, Shujing Shen, Peizhu Hu, Di Geng, Ruipan Zheng, Xingya Li
Summary: This study analyzed the clinical outcomes of ALK-positive NSCLC patients receiving different TKIs and found that alectinib had better PFS compared to crizotinib in first-line treatment, especially in terms of intracranial efficacy. Patients with EML4-ALK gene variants had a better prognosis compared to those without. TP53 co-mutations were associated with adverse outcomes in ALK-positive patients. Furthermore, alectinib might have a better PFS compared to ceritinib and brigatinib after crizotinib failure.
Article
Oncology
Sonia Singh, Adnan A. Jaigirdar, Flora Mulkey, Joyce Cheng, Salaheldin S. Hamed, Yangbing Li, Jiang Liu, Hong Zhao, Anwar Goheer, Whitney S. Helms, Xing Wang, Rajiv Agarwal, Rajan Pragani, Kwadwo Korsah, Shenghui Tang, John Leighton, Atiqur Rahman, Julia A. Beaver, Richard Pazdur, Marc R. Theoret, Harpreet Singh
Summary: The FDA granted accelerated approval for lurbinectedin in treating adult patients with metastatic small cell lung cancer on June 15, 2020. This approval represented the first drug approved by the FDA in over 20 years in the second line for patients with metastatic SCLC.
CLINICAL CANCER RESEARCH
(2021)
Article
Multidisciplinary Sciences
Anna M. Schlafli, Igor Tokarchuk, Sarah Parejo, Susanne Jutzi, Sabina Berezowska, Nikolai Engedal, Mario P. Tschan
Summary: The study shows that ALK inhibition induces LC3B-independent macroautophagic flux in EML4-ALK(+) cells to support cancer cell survival and clonogenic growth.
SCIENTIFIC REPORTS
(2021)
Review
Oncology
Serena Ceddia, Giovanni Codacci-Pisanelli
Summary: Brain metastases are common in patients with ALK-translocated non-small cell lung cancer and are typically treated with radiotherapy. However, this can lead to severe late toxic side effects, prompting the use of ALK inhibitors such as crizotinib, alectinib, and brigatinib which have shown excellent activity against brain metastases. Starting treatment with specific inhibitors in asymptomatic patients and using radiotherapy when needed provides the best quality of life for patients.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Oncology
Sameera Kumar, Xiaoliang Wang, Harlan Pittell, Gregory S. Calip, Stephanie E. Weiss, Joshua E. Meyer, Trevor J. Royce
Summary: This study investigated the use of CNS-Directed RT in NSCLC patients on first-line ALK inhibitors and found a decreasing trend. The findings suggest that physicians may be deferring upfront local therapy for BM in favor of novel targeted agents with improved CNS activity.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Editorial Material
Oncology
Shelley Kuang, Natasha B. Leighl
Summary: The study in NEJM examined whether lorlatinib should be the standard first-line treatment for advanced ALK-rearranged lung cancer.
Article
Oncology
Kunyan Sun, Ligong Nie, Lin Nong, Yuan Cheng
Summary: In this study, a rare case of STRN-ALK-positive NSCLC was reported, showing primary resistance to first-line therapy with alectinib and limited clinical activity of crizotinib in the alectinib-resistant setting. This highlights the need for further research on the response of patients with rare ALK rearrangements to tyrosine kinase inhibitors.
Article
Oncology
Chuangzhou Rao, Liangqin Nie, Xiaokang Wu, Xiaobo Miao, Ting Chen, Liuxi Chen, Dongqing Zhang, Quan Lin
Summary: This study reports two cases of NSCLC patients who acquired the ALK C1156F mutation during treatment with crizotinib. Both patients achieved prolonged progression-free survival after subsequent treatment with alectinib. This is the first clinical evidence that NSCLC patients harboring the acquired ALK C1156F mutation are resistant to crizotinib but sensitive to alectinib.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Rui Xiong, Haitan Fu, Qianrui Zhang, Wei Li
Summary: This study evaluated the efficacy and toxicity of alectinib compared with crizotinib and provided evidence for its clinical use. Three RCTs and six studies were included in the analysis. Alectinib demonstrated superior progress-free survival (PFS) and objective response rate (ORR) compared to crizotinib. The safety profile of alectinib was also favorable with fewer grade 3-5 adverse events. However, the difference in overall survival (OS) between the two drugs was not statistically significant. Further studies with long-term survival data are needed to confirm these findings.
PAKISTAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biotechnology & Applied Microbiology
Hironori Satoh, Yusuke Okuma, Jumpei Kashima, Aya Konno-Yamamoto, Yasushi Yatabe, Yuichiro Ohe
Summary: This case report described a 32-year-old female patient with ALK-rearranged non-small cell lung cancer presenting with miliary pulmonary metastasis and elevated serum amylase level. Treatment with alectinib resulted in regression of CT findings and decrease in serum amylase level. It emphasizes the importance of comprehensive driver mutation testing in young patients with miliary pulmonary metastasis.
ONCOTARGETS AND THERAPY
(2021)
Article
Oncology
Rafal Dziadziuszko, Matthew G. Krebs, Filippo De Braud, Salvatore Siena, Alexander Drilon, Robert C. Doebele, Manish R. Patel, Byoung Chul Cho, Stephen V. Liu, Myung-Ju Ahn, Chao-Hua Chiu, Anna F. Farago, Chia-Chi Lin, Christos S. Karapetis, Yu-Chung Li, Bann-mo Day, David Chen, Timothy R. Wilson, Fabrice Barlesi
Summary: Entrectinib continues to show a high level of clinical benefit for patients with ROS1 fusion-positive NSCLC, including those with central nervous system metastases.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Laura Q. M. Chow, Fabrice Barlesi, Erin M. Bertino, Martin J. van den Bent, Heather A. Wakelee, Patrick Y. Wen, Chao-Hua Chiu, Sergey Orlov, Rita Chiari, Margarita Majem, Mark McKeage, Chong-Jen Yu, Pilar Garrido, Felipe K. Hurtado, Pilar Cazorla Arratia, Yuanbo Song, Fabrice Branle, Michael Shi, Dong-Wan Kim
Summary: This study evaluated the efficacy and safety of the ALK inhibitor ceritinib in patients with ALK(+) NSCLC with brain metastases and/or leptomeningeal disease. The results showed that ceritinib demonstrated anti-tumor activity in these patients.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Satoshi Watanabe, Kazuko Sakai, Naoya Matsumoto, Jun Koshio, Akira Ishida, Tetsuya Abe, Daisuke Ishikawa, Tomohiro Tanaka, Ami Aoki, Tomosue Kajiwara, Kenichi Koyama, Satoru Miura, Yuka Goto, Tomoki Sekiya, Ryo Suzuki, Kohei Kushiro, Toshiya Fujisaki, Naohiro Yanagimura, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Yu Saida, Hirohisa Yoshizawa, Kazuto Nishio, Toshiaki Kikuchi
Summary: Patients with ALK-positive lung cancer after failure of ALK-tyrosine kinase have limited treatment options. This study demonstrates that the combination of alectinib and bevacizumab shows clinical efficacy with acceptable toxicity in these patients.
Article
Multidisciplinary Sciences
Bin Wang, Yang Song, Zhuo Chen, Xiaona Su, Xin Yang, Zhi Wei, Junxia Chen, Chuan Chen, Mengxia Li
Summary: This study aimed to investigate the therapeutic effect and safety of ALK inhibitor in ALK-positive lung cancer patients. A total of 59 patients were recruited and divided into two groups: conventional adjuvant chemotherapy and targeted therapy with crizotinib. The results showed that targeted therapy significantly improved disease-free survival (DFS) and overall survival (OS) compared to adjuvant chemotherapy (P < 0.05). Elevated aspartate transaminase/alanine aminotransferase, nausea, and vomiting were the most common adverse events observed.
SCIENTIFIC REPORTS
(2023)
Article
Urology & Nephrology
David M. Charytan, Jie Yu, Meg J. Jardine, Christopher P. Cannon, Rajiv Agarwal, George Bakris, Tom Greene, Adeera Levin, Carol Pollock, Neil R. Powe, Clare Arnott, Kenneth W. Mahaffey
Summary: The inclusion of race in the calculation of eGFR using different equations had varying effects on the screening and recruitment of participants in the CREDENCE trial, with potential implications on event rates and participant demographics. However, treatment effects remained consistent across different eGFR categories, highlighting the importance of considering race in clinical trials design and analysis.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Transplantation
Jennifer B. Green, Amy K. Mottl, George Bakris, Hiddo J. L. Heerspink, Johannes F. E. Mann, Janet B. McGill, Masaomi Nangaku, Peter Rossing, Charlie Scott, Alain Gay, Rajiv Agarwal
Summary: This study aims to investigate the efficacy of dual therapy with finerenone and an SGLT2i in reducing chronic kidney disease and type 2 diabetes. The results will provide important insights for improving treatment methods for kidney disease and cardiovascular risks.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
Peter Rossing, Rajiv Agarwal, Stefan D. Anker, Gerasimos Filippatos, Bertram Pitt, Luis M. Ruilope, Vivian Fonseca, Guillermo E. Umpierrez, Maria Luiza Caramori, Amer Joseph, Marc Lambelet, Robert Lawatscheck, George L. Bakris
Summary: This study investigated the effect of GLP-1RA use on the outcomes of patients with CKD and T2D treated with finerenone. The results showed that the use of GLP-1RA did not affect the cardiorenal benefits of finerenone.
DIABETES OBESITY & METABOLISM
(2023)
Review
Transplantation
Panagiotis Georgianos, Georgios Tziatzios, Stefanos Roumeliotis, Vasilios Vaios, Vasiliki Sgourogoulou, Dimitrios G. Tsalikakis, Vassilios Liakopoulos, Rajiv Agarwal
Summary: This meta-analysis study found that the use of ACEIs/ARBs is not associated with a significantly lower risk of cardiovascular events and all-cause mortality among patients on dialysis when compared with placebo or no add-on treatment.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Urology & Nephrology
Rajiv Agarwal, James Burton, Maurizio Gallieni, Kamyar Kalantar-Zadeh, Gert Mayer, Carol Pollock, Jacek C. Szepietowski
Summary: Despite the limited increase in life expectancy for patients with end-stage kidney disease after the breakthrough of kidney replacement therapy, the quality of life and relief of symptoms have become increasingly important to patients. Currently, most dialysis-associated symptoms and adverse effects do not have approved treatments, and the few available treatments may add further adverse effects. This article demonstrates how understanding the pathophysiology of a particular symptom (chronic kidney disease-associated pruritus) in dialysis led to the development and regulatory approval of a treatment for that symptom. This approach can be applied to other dialysis-associated symptoms, improving the remaining years of patients' lives.
CLINICAL KIDNEY JOURNAL
(2023)
Article
Urology & Nephrology
Rajiv Agarwal, Bertram Pitt, Biff F. Palmer, Csaba P. Kovesdy, Ellen Burgess, Gerasimos Filippatos, Jolanta Malyszko, Luis M. Ruilope, Patrick Rossignol, Peter Rossing, Roberto Pecoits-Filho, Stefan D. Anker, Amer Joseph, Robert Lawatscheck, Daniel Wilson, Martin Gebel, George L. Bakris
Summary: This study compared the differences in blood pressure reduction and hyperkalemia risk between nonsteroidal MRA finerenone and steroidal MRA spironolactone +/- a potassium binder in patients with treatment-resistant hypertension and chronic kidney disease. The results showed that finerenone had a lower reduction in blood pressure and lower risk of hyperkalemia and treatment discontinuation compared to spironolactone with or without patiromer.
CLINICAL KIDNEY JOURNAL
(2023)
Review
Peripheral Vascular Disease
Panagiotis Georgianos, Rajiv Agarwal
Summary: Steroidal mineralocorticoid-receptor-antagonists (MRAs) have limited use in high-risk patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) due to the associated risk of hyperkalemia and hormonal side effects. Finerenone, a novel nonsteroidal MRA, has shown promising results in reducing cardiovascular and kidney failure outcomes in T2DM patients with a broad spectrum of CKD. Further research is underway to investigate the potential benefits of combining finerenone with a sodium-glucose co-transporter type 2 (SGLT-2) inhibitor.
AMERICAN JOURNAL OF HYPERTENSION
(2023)
Article
Endocrinology & Metabolism
Janet B. B. McGill, Rajiv Agarwal, Stefan D. D. Anker, George L. L. Bakris, Gerasimos Filippatos, Bertram Pitt, Luis M. M. Ruilope, Andreas L. L. Birkenfeld, Maria L. L. Caramori, Meike Brinker, Amer Joseph, Andrea Lage, Robert Lawatscheck, Charlie Scott, Peter Rossing, FIDELIO-DKD Investigator, FIGARO-DKD Investigator
Summary: The aim of this study was to evaluate the effect of finerenone on cardiorenal outcomes and diabetes progression, and to assess its interaction with baseline HbA1c, HbA1c variability, diabetes duration and baseline insulin use. The results showed consistent risk reductions in cardiovascular and kidney outcomes with finerenone compared to placebo across subgroups. Higher HbA1c variability was associated with an increased risk of cardiorenal outcomes. The study concludes that finerenone is effective regardless of baseline characteristics. Overall, the study is rated 9 out of 10.
DIABETES OBESITY & METABOLISM
(2023)
Article
Peripheral Vascular Disease
Rajiv Agarwal, Luis M. Ruilope, Gema Ruiz-Hurtado, Hermann Haller, Roland E. Schmieder, Stefan D. Anker, Gerasimos Filippatos, Bertram Pitt, Peter Rossing, Marc Lambelet, Christina Nowack, Peter Kolkhof, Amer Joseph, George L. Bakris
Summary: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, was found to reduce 24-hour, daytime, and nighttime systolic blood pressure in patients with chronic kidney disease and type 2 diabetes.
JOURNAL OF HYPERTENSION
(2023)
Editorial Material
Transplantation
Rajiv Agarwal, Denis Fouque
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
David Z. I. Cherney, Ele Ferrannini, Guillermo E. Umpierrez, Anne L. Peters, Julio Rosenstock, David R. Powell, Michael J. Davies, Phillip Banks, Rajiv Agarwal
Summary: This study assessed the efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease. The results showed that sotagliflozin 400 mg significantly reduced HbA1c at 26 weeks, while the 200 mg dose did not show significant reduction. The urine albumin-creatinine ratio decreased at 26 weeks, but the improvements were not sustained at 52 weeks. Adverse events were similar between treatment groups.
DIABETES OBESITY & METABOLISM
(2023)
Article
Cardiac & Cardiovascular Systems
Robert A. Fletcher, Clare Arnott, Patrick Rockenschaub, Aletta E. Schutte, Lewis Carpenter, Muthiah Vaduganathan, Rajiv Agarwal, George Bakris, Tara I. Chang, Hiddo J. L. Heerspink, Meg J. Jardine, Kenneth W. Mahaffey, Bruce Neal, Carol Pollock, Min Jun, Anthony Rodgers, Vlado Perkovic, Brendon L. Neuen
Summary: Using data from CANVAS and CREDENCE trials, this study found that visit-to-visit blood pressure variability is independently associated with the risks of hospitalization for heart failure and all-cause mortality in patients with type 2 diabetes and high cardiovascular risk or chronic kidney disease. However, the use of canagliflozin has little to no effect on blood pressure variability.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Transplantation
Panagiotis Georgianos, Rajiv Agarwal
Summary: Hypertension is common and poorly controlled in patients with chronic kidney disease (CKD). Accurate BP measurement is crucial. Dietary sodium restriction and the use of renin-angiotensin system blockers are recommended. Thiazide-like diuretic chlorthalidone is effective in patients with stage 4 CKD and uncontrolled hypertension.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Urology & Nephrology
Rajiv Agarwal, Sanjeev Anand, Kai-Uwe Eckardt, Wenli Luo, Patrick S. Parfrey, Mark J. Sarnak, Christine M. Solinsky, Dennis L. Vargo, Wolfgang C. Winkelmayer, Glenn M. Chertow
Summary: Anemia is common in chronic kidney disease (CKD) and has negative impacts on quality of life and cardiovascular outcomes. Current standard of care for anemia in CKD requires chronic injections, making it less accessible to certain patients. Safety concerns have also been raised regarding the use of erythropoiesis-stimulating agents. The orally active vadadustat may offer advantages over these agents by activating endogenous erythropoietin production.
AMERICAN JOURNAL OF NEPHROLOGY
(2023)
Meeting Abstract
Endocrinology & Metabolism
J. B. Green, A. K. Mottl, G. Bakris, H. J. L. Heerspink, J. F. E. Mann, J. B. McGill, M. Nangaku, P. Rossing, C. Scott, A. Gay, R. Agarwal