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https://www.readbyqxmd.com/read/29773717/stk11-lkb1-mutations-and-pd-1-inhibitor-resistance-in-kras-mutant-lung-adenocarcinoma
#1
Ferdinandos Skoulidis, Michael E Goldberg, Danielle M Greenawalt, Matthew D Hellmann, Mark M Awad, Justin F Gainor, Alexa B Schrock, Ryan J Hartmaier, Sally E Trabucco, Laurie Gay, Siraj M Ali, Julia A Elvin, Gaurav Singal, Jeffrey S Ross, David Fabrizio, Peter M Szabo, Han Chang, Ariella Sasson, Sujaya Srinivasan, Stefan Kirov, Joseph Szustakowski, Patrik Vitazka, Robin Edwards, Jose A Bufill, Neelesh Sharma, Sai-Hong I Ou, Nir Peled, David R Spigel, Hira Rizvi, Elizabeth Jimenez Aguilar, Brett W Carter, Jeremy Erasmus, Darragh F Halpenny, Andrew J Plodkowski, Niamh M Long, Mizuki Nishino, Warren L Denning, Ana Galan-Cobo, Haifa Hamdi, Taghreed Hirz, Pan Tong, Jing Wang, Jaime Rodriguez-Canales, Pamela A Villalobos, Edwin R Parra, Neda Kalhor, Lynette M Sholl, Jennifer L Sauter, Achim A Jungbluth, Mari Mino-Kenudson, Roxana Azimi, Yasir Y Elamin, Jianjun Zhang, Giulia C Leonardi, Fei Jiang, Kwok-Kin Wong, J Jack Lee, Vassiliki A Papadimitrakopoulou, Ignacio I Wistuba, Vincent A Miller, Garrett M Frampton, Jedd D Wolchok, Alice T Shaw, Pasi A Jänne, Philip J Stephens, Charles M Rudin, William J Geese, Lee A Albacker, John V Heymach
KRAS is the most common oncogenic driver in lung adenocarcinoma (LUAC). We previously reported that STK11/LKB1 (KL) or TP53 (KP) co-mutations define distinct subgroups of KRAS-mutant LUAC. Here, we examine the efficacy of PD-1 inhibitors in these subgroups. Objective response rates to PD-1 blockade differed significantly among KL (7.4%), KP (35.7%), and K-only (28.6%) subgroups (P<0.001) in the SU2C cohort (174 patients) with KRAS-mutant LUAC and in patients treated with nivolumab in the CheckMate-057 phase 3 trial (0% vs 57...
May 17, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29731394/tumor-mutational-burden-and-efficacy-of-nivolumab-monotherapy-and-in-combination-with-ipilimumab-in-small-cell-lung-cancer
#2
Matthew D Hellmann, Margaret K Callahan, Mark M Awad, Emiliano Calvo, Paolo A Ascierto, Akin Atmaca, Naiyer A Rizvi, Fred R Hirsch, Giovanni Selvaggi, Joseph D Szustakowski, Ariella Sasson, Ryan Golhar, Patrik Vitazka, Han Chang, William J Geese, Scott J Antonia
Durable responses and encouraging survival have been demonstrated with immune checkpoint inhibitors in small-cell lung cancer (SCLC), but predictive markers are unknown. We used whole exome sequencing to evaluate the impact of tumor mutational burden on efficacy of nivolumab monotherapy or combined with ipilimumab in patients with SCLC from the nonrandomized or randomized cohorts of CheckMate 032. Patients received nivolumab (3 mg/kg every 2 weeks) or nivolumab plus ipilimumab (1 mg/kg plus 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks)...
April 21, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29728867/check-point-inhibitors-a-new-era-in-renal-cell-carcinoma-treatment
#3
REVIEW
Mohamed Alsharedi, Heather Katz
In the United States, the estimated number of new cases of renal cell carcinoma (RCC) is approximately 65,000 case with about 15,000 deaths in the year of 2018 (Siegel et al. in CA Cancer J Clin 68(1):7, 2018). RCC as an immunogenic malignancy is supported by many theories and facts which include tumor richness of lymphocytes infiltrate, the occurrence of spontaneous tumor regression, and the proved effect of traditional immunotherapy (Finke et al. in J Immunother 11(1):1-11, 1992), all these factors support the potential therapeutic effect of the novel immunotherapeutic agents in RCC...
May 4, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29727313/nivolumab-in-the-treatment-of-metastatic-renal-cell-carcinoma-a-cost-utility-analysis
#4
Jacques Raphael, Zhuolu Sun, Georg A Bjarnason, Joelle Helou, Beate Sander, David M Naimark
INTRODUCTION: Nivolumab improves overall survival and health-related quality of life compared with everolimus in metastatic renal cell carcinoma (mRCC). This study assesses the cost-utility of nivolumab from the Canadian health care payer perspective. MATERIALS AND METHODS: To evaluate the cost-utility of nivolumab, a Markov cohort model that incorporated data from the phase 3 CheckMate-025 trial and other sources was developed. The incremental cost per quality-adjusted life month (QALM) gained for nivolumab was calculated...
May 4, 2018: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29714652/real-world-evidence-in-metastatic-renal-cell-carcinoma
#5
Jeffrey Graham, Daniel Yc Heng
Real-world evidence has played an important role in expanding our knowledge on the treatment and prognostication of advanced renal cell carcinoma. This type of data has been particularly helpful in providing a better understanding of groups that are traditionally excluded from randomized controlled trials. The International mRCC Database Consortium (IMDC) represents the largest collection of real-world data on patients with advanced kidney cancer treated with targeted therapies. The IMDC prognostic model has been used to stratify patients in contemporary clinical trials and to provide risk-directed treatment selection in everyday clinical practice...
March 1, 2018: Tumori
https://www.readbyqxmd.com/read/29691222/checkpoint-checkmate-microbiota-modulation-of-cancer-immunotherapy
#6
Eric C Keen, Terence S Crofts, Gautam Dantas
No abstract text is available yet for this article.
April 24, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29682332/gender-and-outcomes-in-non-small-cell-lung-cancer-an-old-prognostic-variable-comes-back-for-targeted-therapy-and-immunotherapy
#7
Joseph A Pinto, Carlos S Vallejos, Luis E Raez, Luis A Mas, Rossana Ruiz, Junior S Torres-Roman, Zaida Morante, Jhajaira M Araujo, Henry L Gómez, Alfredo Aguilar, Denisse Bretel, Claudio J Flores, Christian Rolfo
Background: There are well-known differences in gender outcome in non-small cell lung cancer (NSCLC) and other cancers. In this work, we evaluated several randomised clinical trials to explore the gender influence in the outcome of patients with NSCLC treated with targeted therapy and immunotherapy. Methods: We performed a series of meta-analysis to compare the gender outcome in the routine setting for overall survival and progression-free survival (PFS) in phase III randomised clinical trials comparing EGFR inhibitors versus chemotherapy (OPTIMAL, LUX-lung 3, LUX-lung 6, EURTAC, ENSURE and WTJOG); ALK inhibitors versus chemotherapy (ASCEND 4, ASCEND 5, PROFILE 1014 and NCT009323893) and anti-PD1 checkpoint inhibitors versus chemotherapy (CheckMate 017, CheckMate 026, CheckMate 057, KEYNOTE 010 and KEYNOTE 024)...
2018: ESMO Open
https://www.readbyqxmd.com/read/29669553/significant-response-to-nivolumab-for-metastatic-chromophobe-renal-cell-carcinoma-with-sarcomatoid-differentiation-a-case-report
#8
Go Noguchi, Sohgo Tsutsumi, Masato Yasui, Shinji Ohtake, Susumu Umemoto, Noboru Nakaigawa, Masahiro Yao, Takeshi Kishida
BACKGROUND: The treatment of advanced or metastatic renal cell carcinoma (RCC) has drastically changed since the approval of immune checkpoint therapy. Nivolumab is a treatment option for patients with metastatic RCC, previously treated with targeted antiangiogenic therapy. The efficacy of nivolumab for patients with RCC was established by the Checkmate 025 clinical trial. Chromophobe RCC (CRCC) represents around 5% of RCC cases, but non-clear cell RCC (non-ccRCC) subtypes were excluded from the Checkmate 025 clinical trial...
April 18, 2018: BMC Urology
https://www.readbyqxmd.com/read/29669246/tgf-%C3%AE-inhibition-and-immunotherapy-checkmate
#9
Karuna Ganesh, Joan Massagué
Immune checkpoint therapy can induce durable remissions, but many tumors demonstrate resistance. In a recent issue of Nature, Mariathasan et al. (2018) and Tauriello et al. (2018) identify stromal TGF-β signaling as a determinant of immune exclusion. Combination TGF-β inhibition and immunotherapy induces complete responses in mouse models.
April 17, 2018: Immunity
https://www.readbyqxmd.com/read/29666934/quo-vadis-do-immunotherapies-have-a-role-in-glioblastoma
#10
REVIEW
Sylvia C Kurz, Patrick Y Wen
PURPOSE OF REVIEW: More effective therapies for glioblastoma are urgently needed. Immunotherapeutic strategies appear particularly promising and are therefore intensively studied. This article reviews the current understanding of the immunosuppressive glioblastoma microenvironment, discusses the rationale behind various immunotherapies, and outlines the findings of several recently published clinical studies. RECENT FINDINGS: The results of CheckMate-143 indicated that nivolumab is not superior to bevacizumab in patients with recurrent glioblastoma...
April 18, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29666439/checkmate-214-a-winning-combination
#11
Diana Romero
No abstract text is available yet for this article.
April 17, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29661758/high-tmb-predicts-immunotherapy-benefit-in-nsclc
#12
(no author information available yet)
The first data from the phase III CheckMate-227 trial of ipilimumab plus nivolumab for the treatment of non-small cell lung cancer suggests that the two drugs boost progression-free survival in patients with a high tumor mutation burden. After 1 year, progression-free survival was 43% for patients treated with the checkpoint inhibitor combination, compared with 13% for patients treated with chemotherapy.
April 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29658845/nivolumab-plus-ipilimumab-in-lung-cancer-with-a-high-tumor-mutational-burden
#13
Matthew D Hellmann, Tudor-Eliade Ciuleanu, Adam Pluzanski, Jong Seok Lee, Gregory A Otterson, Clarisse Audigier-Valette, Elisa Minenza, Helena Linardou, Sjaak Burgers, Pamela Salman, Hossein Borghaei, Suresh S Ramalingam, Julie Brahmer, Martin Reck, Kenneth J O'Byrne, William J Geese, George Green, Han Chang, Joseph Szustakowski, Prabhu Bhagavatheeswaran, Diane Healey, Yali Fu, Faith Nathan, Luis Paz-Ares
Background Nivolumab plus ipilimumab showed promising efficacy for the treatment of non-small-cell lung cancer (NSCLC) in a phase 1 trial, and tumor mutational burden has emerged as a potential biomarker of benefit. In this part of an open-label, multipart, phase 3 trial, we examined progression-free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden (≥10 mutations per megabase). Methods We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy...
April 16, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29623227/fulminant-diabetes-in-a-patient-with-advanced-melanoma-on-nivolumab
#14
Nora Chokr, Hafsa Farooq, Elizabeth Guadalupe
Background: Anti-PD-1 agents were approved for advanced melanoma after the landmark trial Checkmate-037. Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells in genetically predisposed people. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy. Case: A 61-year-old male with advanced melanoma presented with a three-day history of nausea, vomiting, and malaise...
2018: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/29587324/-immunotherapy-for-renal-cell-carcinoma-current-status
#15
Marc-Oliver Grimm, Susan Foller
Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs...
April 2018: Aktuelle Urologie
https://www.readbyqxmd.com/read/29584546/nivolumab-for-relapsed-refractory-classic-hodgkin-lymphoma-after-failure-of-autologous-hematopoietic-cell-transplantation-extended-follow-up-of-the-multicohort-single-arm-phase-ii-checkmate-205-trial
#16
Philippe Armand, Andreas Engert, Anas Younes, Michelle Fanale, Armando Santoro, Pier Luigi Zinzani, John M Timmerman, Graham P Collins, Radhakrishnan Ramchandren, Jonathon B Cohen, Jan Paul De Boer, John Kuruvilla, Kerry J Savage, Marek Trneny, Margaret A Shipp, Kazunobu Kato, Anne Sumbul, Benedetto Farsaci, Stephen M Ansell
Purpose Genetic alterations causing overexpression of programmed death-1 ligands are near universal in classic Hodgkin lymphoma (cHL). Nivolumab, a programmed death-1 checkpoint inhibitor, demonstrated efficacy in relapsed/refractory cHL after autologous hematopoietic cell transplantation (auto-HCT) in initial analyses of one of three cohorts from the CheckMate 205 study of nivolumab for cHL. Here, we assess safety and efficacy after extended follow-up of all three cohorts. Methods This multicenter, single-arm, phase II study enrolled patients with relapsed/refractory cHL after auto-HCT treatment failure into cohorts by treatment history: brentuximab vedotin (BV)-naïve (cohort A), BV received after auto-HCT (cohort B), and BV received before and/or after auto-HCT (cohort C)...
March 27, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/29562145/nivolumab-plus-ipilimumab-versus-sunitinib-in-advanced-renal-cell-carcinoma
#17
Robert J Motzer, Nizar M Tannir, David F McDermott, Osvaldo Arén Frontera, Bohuslav Melichar, Toni K Choueiri, Elizabeth R Plimack, Philippe Barthélémy, Camillo Porta, Saby George, Thomas Powles, Frede Donskov, Victoria Neiman, Christian K Kollmannsberger, Pamela Salman, Howard Gurney, Robert Hawkins, Alain Ravaud, Marc-Oliver Grimm, Sergio Bracarda, Carlos H Barrios, Yoshihiko Tomita, Daniel Castellano, Brian I Rini, Allen C Chen, Sabeen Mekan, M Brent McHenry, Megan Wind-Rotolo, Justin Doan, Padmanee Sharma, Hans J Hammers, Bernard Escudier
Background Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. Methods We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle)...
March 21, 2018: New England Journal of Medicine
https://www.readbyqxmd.com/read/29560755/nivolumab-in-squamous-cell-carcinoma-of-the-head-and-neck
#18
Pol Specenier
The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC. Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab)...
May 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29534940/nivolumab-is-a-cost-effective-second-line-treatment-for-metastatic-renal-cell-carcinoma
#19
Jacopo Giuliani, Andrea Bonetti
INTRODUCTION: The introduction of active new agents, such as small molecules and checkpoint inhibitors, for the treatment of metastatic renal-cell cancer (mRCC) is associated with a relevant increase in costs, and it is therefore important to strike a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression-free survival (PFS) and overall survival (OS). METHODS: This analysis was conducted to assess the pharmacologic costs of second-line treatments for mRCC and was restricted to pivotal phase 3 randomized controlled trials (RCTs) used as second-line therapy...
February 22, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29518553/phase-1-2-study-of-the-safety-and-tolerability-of-nivolumab-plus-crizotinib-for-the-first-line-treatment-of-anaplastic-lymphoma-kinase-translocation-positive-advanced-non-small-cell-lung-cancer-checkmate-370
#20
David R Spigel, Craig Reynolds, David Waterhouse, Edward B Garon, Jason Chandler, Sunil Babu, Paul Thurmes, Alexander Spira, Robert Jotte, Jin Zhu, Wen Hong Lin, George Blumenschein
INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses...
May 2018: Journal of Thoracic Oncology
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