Author
Amishi Yogesh Shah
Other affiliations: University of Texas Health Science Center at Houston, University of Texas at Austin
Bio: Amishi Yogesh Shah is an academic researcher from University of Texas MD Anderson Cancer Center. The author has contributed to research in topics: Medicine & Nivolumab. The author has an hindex of 12, co-authored 85 publications receiving 731 citations. Previous affiliations of Amishi Yogesh Shah include University of Texas Health Science Center at Houston & University of Texas at Austin.
Topics: Medicine, Nivolumab, Internal medicine, Renal cell carcinoma, Sunitinib
Papers
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Brigham and Women's Hospital1, Queen Mary University of London2, Institut Gustave Roussy3, Universidad Autónoma de Nuevo León4, Washington University in St. Louis5, University of Pavia6, University of Texas MD Anderson Cancer Center7, Royal Brisbane and Women's Hospital8, University of Colorado Denver9, Niigata University10, University of Tübingen11, Bristol-Myers Squibb12, Exelixis13, National Institutes of Health14, Memorial Sloan Kettering Cancer Center15
TL;DR: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma.
Abstract: Background The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. ...
816 citations
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TL;DR: Initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4 warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadJuvant treatment.
Abstract: Immune checkpoint therapy is being tested in the neoadjuvant setting for patients with localized urothelial carcinoma1,2, with one study reporting data in cisplatin-ineligible patients who received anti-PD-L1 monotherapy2. The study reported that patients with bulky tumors, a known high-risk feature defined as greater than clinical T2 disease, had fewer responses, with pathological complete response rate of 17%2. Here we report on the first pilot combination neoadjuvant trial (
NCT02812420
) with anti-PD-L1 (durvalumab) plus anti-CTLA-4 (tremelimumab) in cisplatin-ineligible patients, with all tumors identified as having high-risk features (n = 28). High-risk features were defined by bulky tumors, variant histology, lymphovascular invasion, hydronephrosis and/or high-grade upper tract disease3–5. The primary endpoint was safety and we observed 6 of 28 patients (21%) with grade ≥3 immune-related adverse events, consisting of asymptomatic laboratory abnormalities (n = 4), hepatitis and colitis (n = 2). We also observed pathological complete response of 37.5% and downstaging to pT1 or less in 58% of patients who completed surgery (n = 24). In summary, we provide initial safety, efficacy and biomarker data with neoadjuvant combination anti-PD-L1 plus anti-CTLA-4, which warrants further development for patients with localized urothelial carcinoma, especially cisplatin-ineligible patients with high-risk features who do not currently have an established standard-of-care neoadjuvant treatment. Neoadjuvant combination of immune checkpoint therapy in patients with cisplatin-ineligible bladder cancer achieves clinical efficacy and uncovers immune features as potential predictive biomarkers of treatment response.
152 citations
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Harvard University1, Queen Mary University of London2, Universidad Autónoma de Nuevo León3, Washington University in St. Louis4, University of Texas MD Anderson Cancer Center5, Autonomous University of Barcelona6, Pontifícia Universidade Católica do Rio Grande do Sul7, Monash University8, Niigata University9, Institut Gustave Roussy10, Bristol-Myers Squibb11, National Institutes of Health12, Memorial Sloan Kettering Cancer Center13
92 citations
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Memorial Sloan Kettering Cancer Center1, University of Texas Health Science Center at Houston2, University of Minnesota3, Providence Portland Medical Center4, Washington University in St. Louis5, Hospital Universitario La Paz6, Emory University7, Texas Oncology8, University of Chicago9, Akershus University Hospital10, Eisai11, Merck & Co.12
TL;DR: Eisai et al. as discussed by the authors evaluated the combination of lenvatinib plus pembrolizumab in patients with metastatic renal cell carcinoma (RCC) and showed encouraging antitumour activity and manageable safety profile.
Abstract: Summary Background Despite advances in the first-line treatment of metastatic renal cell carcinoma (RCC), there is an unmet need for options to address disease progression during or after treatment with immune checkpoint inhibitors (ICIs). Pembrolizumab and lenvatinib are active as monotherapies in RCC; thus, we aimed to evaluate the combination of lenvatinib plus pembrolizumab in these patients. Methods We report results of the metastatic RCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients aged at least 18 years with selected solid tumours and an Eastern Cooperative Oncology Group performance status of 0–1. Oral lenvatinib at 20 mg was given once daily along with intravenous pembrolizumab at 200 mg once every 3 weeks. Patients remained on study drug treatment until disease progression, development of unacceptable toxicity, or withdrawal of consent. Efficacy was analysed in patients with clear cell metastatic RCC receiving study drug by previous therapy grouping: treatment naive, previously treated ICI naive (previously treated with at least one line of therapy but not with an anti-PD-1 or anti-PD-L1 ICI), and ICI pretreated (ie, anti-PD-1 or anti-PD-L1) patients. Safety was analysed in all enrolled and treated patients. The primary endpoint was the objective response rate at week 24 per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. This trial is registered with ClinicalTrials.gov ( NCT02501096 ) and with the EU Clinical Trials Register (EudraCT2017-000300-26), and is closed to new participants. Findings Between July 21, 2015, and Oct 16, 2019, 145 patients were enrolled in the study. Two patients had non-clear cell RCC and were excluded from the efficacy analysis (one in the treatment-naive group and one in the ICI-pretreated group); thus, the population evaluated for efficacy comprised 143 patients (n=22 in the treatment-naive group, n=17 in the previously treated ICI-naive group, and n=104 in the ICI-pretreated group). All 145 enrolled patients were included in the safety analysis. The median follow-up was 19·8 months (IQR 14·3–28·4). The number of patients with an objective response at week 24 by irRECIST was 16 (72·7%, 95% CI 49·8–89·3) of 22 treatment-naive patients, seven (41·2%, 18·4–67·1) of 17 previously treated ICI-naive patients, and 58 (55·8%, 45·7–65·5) of 104 ICI-pretreated patients. Of 145 patients, 82 (57%) had grade 3 treatment-related adverse events and ten (7%) had grade 4 treatment-related adverse events. The most common grade 3 treatment-related adverse event was hypertension (30 [21%] of 145 patients). Treatment-related serious adverse events occurred in 36 (25%) patients, and there were three treatment-related deaths (upper gastrointestinal haemorrhage, sudden death, and pneumonia). Interpretation Lenvatinib plus pembrolizumab showed encouraging antitumour activity and a manageable safety profile and might be an option for post-ICI treatment of metastatic RCC. Funding Eisai and Merck Sharp & Dohme.
85 citations
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TL;DR: 2L antitumour activity and tolerance comparable to historical data for 1L TKI is observed in patients with mccRCC, and forty-five percent of subjects required a dose reduction, and twenty-seven percent of patients discontinued treatment because of toxicity.
74 citations
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TL;DR: The history of muscle‐invasive and advanced bladder cancer management is reviewed, the important molecular characteristics of bladder cancer are highlighted, the major advances in treatment are described, and future directions for therapeutic development are offered.
Abstract: Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has primarily consisted of platinum-based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody-drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle-invasive bladder cancer. Herein, the authors review the history of muscle-invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.
382 citations
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TL;DR: In this article, a renal cell carcinoma who undergo nephrectomy has no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence.
Abstract: Background Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. Me...
294 citations
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TL;DR: In this article, the authors survey the current understanding of mechanisms of response and resistance to ICT and propose a path forward to improving efficacy and minimizing toxicities through better patient selection and rational combinations.
Abstract: Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival However, only subsets of patients with specific tumor types respond to ICT Thus, significant challenges remain, including understanding pathways of resistance, optimizing patient selection, improving management of immune-related adverse events, and identifying rational therapeutic combinations These challenges will need a focused approach encompassing both clinical and basic research, with the integration of reverse translational studies This integrated approach will lead to identification of potential targets for subsequent clinical trials, which will guide decisions as we develop novel combination strategies to maximize efficacy and minimize toxicities for patients SIGNIFICANCE: ICTs induce durable antitumor responses for subsets of patients with cancer Recent evidence suggests that rational combinatorial strategies can improve response by overcoming primary and adaptive resistance mechanisms, although these may carry an increased risk of immune-mediated toxicities This review surveys the current understanding of mechanisms of response and resistance to ICTs and active areas of investigation, and proposes a path forward to improving efficacy and minimizing toxicities through better patient selection and rational combinations
263 citations
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TL;DR: Findings from high-throughput sequencing and gene expression profiling may help in the near future to translate knowledge of HCC biology into clinical practice, and are expected to improve precision medicine for patients with this highly aggressive malignancy.
250 citations
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TL;DR: Current and emerging first-line treatment options, including recent approvals of the tyrosine kinase inhibitor cabozantinib and the immunotherapy combination of nivolumab andipilimumab, and ongoing studies investigating combinations of checkpoint inhibitors with TKIs, and with other novel immunomodulatory agents are reviewed.
233 citations