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https://www.readbyqxmd.com/read/28419328/efficacy-and-safety-of-osimertinib-in-a-japanese-compassionate-use-program
#1
Yutaka Fujiwara, Yasushi Goto, Shintaro Kanda, Hidehito Horinouchi, Noboru Yamamoto, Naomi Sakiyama, Reiko Ando Makihara, Yuichiro Ohe
Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets the T790M mutation of EGFR. In 2016, AstraZeneca conducted a compassionate use program for osimertinib in Japan. Methods: Eighteen consecutive patients with histologically proven non-small-cell lung cancer (NSCLC) and harboring the T790M EGFR mutation participated in the compassionate use program between 1 April and 25 May 2016, at the National Cancer Center Hospital...
April 13, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28419059/late-onset-nivolumab-mediated-pneumonitis-in-a-patient-with-melanoma-and-multiple-immune-related-adverse-events
#2
Panagiotis T Diamantopoulos, Maria Gaggadi, Eva Kassi, Olga Benopoulou, Amalia Anastasopoulou, Helen Gogas
Immune-related adverse effects (AEs) of PD-1 inhibitors can affect almost every organ, but the skin, intestine, lung, eye, and liver are the most commonly affected organs. Here, we present the case of a 62-year-old female patient with stage IIIc melanoma treated with nivolumab in an adjuvant setting who sequentially developed hyperthyroidism, hypothyroidism, acute hepatitis, and pneumonitis. Six months before the emergence of pneumonitis, the patient had discontinued treatment with nivolumab because of acute hepatitis...
April 17, 2017: Melanoma Research
https://www.readbyqxmd.com/read/28418115/aggravation-of-diabetes-and-incompletely-deficient-insulin-secretion-in-a-case-with-type-1-diabetes-resistant-hla-drb1-15-02-treated-with-nivolumab
#3
Kimio Matsumura, Kaoru Nagasawa, Yoichi Oshima, Shouta Kikuno, Kyohei Hayashi, Akihiro Nishimura, Minoru Okubo, Hironori Uruga, Kazuma Kishi, Tetsuro Kobayashi, Yasumichi Mori
Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects especially in endocrine systems. Several cases of acute onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible HLA genotype for type 1 diabetes possibly suggesting that human leukocyte antigen (HLA) might be involved in the onset of diabetes with anti PD-1 therapy. We describe an atypical case of hyperglycemia after anti PD-1 antibody administration. A 68-year-old Japanese man with pancreatic diabetes and steroid diabetes was administered nivolumab three times for chemoresistant adenocarcinoma of the lung...
April 18, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28416123/immune-checkpoint-inhibitors-for-patients-with-advanced-non-small-cell-lung-cancer-a%C3%A2-systematic-review
#4
REVIEW
Peter M Ellis, Emily T Vella, Yee C Ung
Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC...
February 16, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28408617/treatment-paradigms-for-advanced-non-small-cell-lung-cancer-at-academic-medical-centers-involvement-in-clinical-trial-endpoint-design
#5
Charu Aggarwal, Hossein Borghaei
Based on the positive results of various clinical trials, treatment options for non-small cell lung cancer (NSCLC) have expanded greatly over the last 25 years. While regulatory approvals of chemotherapeutic agents for NSCLC have largely been based on improvements in overall survival, recent approvals of many targeted agents for NSCLC (afatinib, crizotinib, ceritinib, osimertinib) have been based on surrogate endpoints such as progression-free survival and objective response. As such, selection of appropriate clinical endpoints for examining the efficacy of investigational agents for NSCLC is of vital importance in clinical trial design...
April 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28407622/prolactin-as-a-potential-early-predictive-factor-in-metastatic-non-small-cell-lung-cancer-patients-treated-with-nivolumab
#6
Salvatore Caponnetto, Giovanni Maria Iannantuono, Giacomo Barchiesi, Valentina Magri, Alain Gelibter, Enrico Cortesi
BACKGROUND/AIMS: Prolactin (PRL) is a peptide hormone and several studies have demonstrated its role as a cytokine in human T cell-mediated immunity. We are unaware if PRL is a positive or negative immunomodulator, but its effects on the regulation of T cells could inhibit the antitumor activity elicited by nivolumab (NIVO). We aimed to assess whether the occurrence of hyperprolactinemia in metastatic non-small cell lung cancer (mNSCLC) patients treated with NIVO is associated with poor clinical outcomes...
April 14, 2017: Oncology
https://www.readbyqxmd.com/read/28407528/immunotherapy-revolutionises-non-small-cell-lung-cancer-therapy-results-perspectives-and-new-challenges
#7
REVIEW
Etienne Giroux Leprieur, Coraline Dumenil, Catherine Julie, Violaine Giraud, Jennifer Dumoulin, Sylvie Labrune, Thierry Chinet
Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10...
April 10, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28407039/tumor-immune-microenvironment-and-nivolumab-efficacy-in-egfr-mutation-positive-non-small-cell-lung-cancer-based-on-t790m-status-after-disease-progression-during-egfr-tki-treatment
#8
K Haratani, H Hayashi, T Tanaka, H Kaneda, Y Togashi, K Sakai, K Hayashi, S Tomida, Y Chiba, K Yonesaka, Y Nonagase, T Takahama, J Tanizaki, K Tanaka, T Yoshida, K Tanimura, M Takeda, H Yoshioka, T Ishida, T Mitsudomi, K Nishio, K Nakagawa
Background.: The efficacy of programmed death-1 (PD-1) blockade in epidermal growth factor receptor gene ( EGFR ) mutation-positive non-small cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR . Patients and Methods.: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A)...
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28393006/small-cell-lung-cancer-transformation-during-immunotherapy-with-nivolumab-a-case-report
#9
Takuma Imakita, Kohei Fujita, Osamu Kanai, Tsuyoshi Terashima, Tadashi Mio
We report a rare case of transformation of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC), without epidermal growth factor receptor (EGFR) gene mutation, during immunotherapy treatment with nivolumab. A 75-year-old man was referred to our hospital following the observation of a 64 mm mass in a chest computed tomography (CT) scan. A transbronchial biopsy of the mass identified the pathological presence of poorly differentiated NSCLC, with no histological signs of SCLC. No mutations were identified in the EGFR gene...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28383639/immune-checkpoint-inhibitors-in-advanced-renal-cell-carcinoma-experience-to-date-and-future-directions
#10
M B Atkins, J I Clark, D I Quinn
In recent years, there has been dramatic expansion of the treatment armamentarium for patients with advanced renal cell carcinoma (aRCC), including drugs targeting vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways. Despite these advances, patient outcomes remain suboptimal, underscoring the need for therapeutic interventions with novel mechanisms of action. The advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for several solid malignancies...
April 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28382561/response-to-the-treatment-immediately-before-nivolumab-monotherapy-may-predict-clinical-response-to-nivolumab-in-patients-with-non-small-cell-lung-cancer
#11
Haruki Kobayashi, Shota Omori, Kazuhisa Nakashima, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Haruyasu Murakami, Masahiro Endo, Toshiaki Takahashi
BACKGROUND: Currently, no markers predictive of response to nivolumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) are currently recognized in Japan. The present study was undertaken to identify such markers. MATERIALS AND METHODS: Medical records of 50 patients with advanced NSCLC and treated with nivolumab monotherapy at Shizuoka Cancer Center between December 2015 and April 2016 were retrospectively reviewed. The parameters studied were age, sex, Eastern Cooperative Oncology Group performance status, smoking history, histological diagnosis, epidermal growth factor receptor or anaplastic lymphoma kinase status, therapeutic line of nivolumab, efficacy of treatment immediately before nivolumab monotherapy, and time since previous therapy...
April 5, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28371614/hypermutations-in-gliomas-a-potential-immunotherapy-target
#12
Gaetano Finocchiaro, Tiziana Langella, Cristina Corbetta, Serena Pellegatta
Checkpoint inhibitors, like ipilimumab, nivolumab, and pembrolizumab, have provided a breakthrough in cancer immunotherapy, such as in the treatment of melanoma and colorectal and lung cancer. The close relationship between the number of mutations (mutational load) and the response to checkpoint immunotherapy has been convincingly demonstrated in these cancers. Hypermutations in tumors are caused by environmental factors, like UV radiations or cigarette smoking, or by germinal mutations affecting genes of the Mismatch Repair (MMR) machinery, as in the Lynch syndrome...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28371397/delayed-pseudoprogression-of-lung-adenocarcinoma-accompanied-with-interstitial-lung-disease-during-chemotherapy-after-nivolumab-treatment
#13
Toru Kumagai, Madoka Kimura, Takako Inoue, Motohiro Tamiya, Kazumi Nishino, Fumio Imamura
A 62-year-old Japanese female with primary lung adenocarcinoma received seven cycles of nivolumab as an eighth line of chemotherapy until she presented with hemoptysis. After transcatheter arterial embolization therapy, she received subsequent chemotherapy with paclitaxel and S-1. Four weeks later, a chest computed tomography examination revealed infiltrative shadows mainly in the right lung field, in addition to enlargement of the lung metastasis in the right middle lung lobe. Bronchofiberscopic examination revealed infiltration of lymphocytes without any malignant cells in the right segment 1 of the lung, which suggested interstitial lung disease...
March 30, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28368440/prior-radiotherapy-does-not-predict-nivolumab-response-in-non-small-cell-lung-cancer-a-retrospective-cohort-study
#14
Y Kataoka, N Ebi, D Fujimoto, S Hara, K Hirano, T Narabayashi, T Tanaka, K Tomii, H Yoshioka
No abstract text is available yet for this article.
March 20, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28344662/nivolumab-in-renal-cell-carcinoma-latest-evidence-and-clinical-potential
#15
REVIEW
Camille Mazza, Bernard Escudier, Laurence Albiges
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s. However, these therapies were effective in only 10-20% of cases and were not well tolerated. Recently, new insights on the interaction between the immune system and tumor have identified the programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) pathway to be a key player in evading host immune responses...
March 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28332580/clinical-impact-of-single-nucleotide-polymorphism-in-pd-l1-on-response-to-nivolumab-for-advanced-non-small-cell-lung-cancer-patients
#16
Takashi Nomizo, Hiroaki Ozasa, Takahiro Tsuji, Tomoko Funazo, Yuto Yasuda, Hironori Yoshida, Yoshitaka Yagi, Yuichi Sakamori, Hiroki Nagai, Toyohiro Hirai, Young Hak Kim
This study was intended to determine the efficacy of nivolumab, we evaluated treatment response with respect to PD-1/PD-L1 SNPs among patients with NSCLC. A total of 50 patients with NSCLC were treated with nivolumab and were also evaluated for PD-1/PD-L1 single nucleotide polymorphisms (SNPs) from plasma DNA. We investigated the association among PD-1/PD-L1 SNPs, objective response rate (ORR) and progression-free survival (PFS). Two of seven SNPs studied showed association with ORR and PFS, with maximum evidence at the marker rs2282055...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326832/nintedanib-plus-docetaxel-as-second-line-therapy-in-patients-with-non-small-cell-lung-cancer-of-adenocarcinoma-histology-a-network-meta-analysis-vs-new-therapeutic-options
#17
Sanjay Popat, Anders Mellemgaard, Martin Reck, Claudia Hastedt, Ingolf Griebsch
PATIENTS & METHODS: We provide an update to a network meta-analysis evaluating the relative efficacy of nintedanib + docetaxel versus other second-line agents in adenocarcinoma histology non-small-cell lung cancer. RESULTS: Overall similarity of nintedanib + docetaxel versus ramucirumab + docetaxel, and versus nivolumab. Comparing nintedanib + docetaxel with nivolumab, hazards ratio (HR) of overall survival and progression-free survival (PFS) pointed in opposite directions (overall survival: HR: 1...
February 27, 2017: Future Oncology
https://www.readbyqxmd.com/read/28317087/imaging-and-clinicopathological-features-of-nivolumab-related-cholangitis-in-patients-with-non-small-cell-lung-cancer
#18
Hisato Kawakami, Junko Tanizaki, Kaoru Tanaka, Koji Haratani, Hidetoshi Hayashi, Masayuki Takeda, Ken Kamata, Mamoru Takenaka, Masatomo Kimura, Takaaki Chikugo, Takao Sato, Masatoshi Kudo, Akihiko Ito, Kazuhiko Nakagawa
Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3...
March 20, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28314688/nivolumab-treatment-for-oesophageal-squamous-cell-carcinoma-an-open-label-multicentre-phase-2-trial
#19
Toshihiro Kudo, Yasuo Hamamoto, Ken Kato, Takashi Ura, Takashi Kojima, Takahiro Tsushima, Shuichi Hironaka, Hiroki Hara, Taroh Satoh, Satoru Iwasa, Kei Muro, Hirofumi Yasui, Keiko Minashi, Kensei Yamaguchi, Atsushi Ohtsu, Yuichiro Doki, Yuko Kitagawa
BACKGROUND: Nivolumab is a human monoclonal IgG4 antibody that inhibits programmed cell death protein 1 (PD-1) expressed on activated T cells. We investigated the safety and activity of nivolumab in patients with treatment-refractory oesophageal cancer. METHODS: We did an open-label, single-arm, multicentre phase 2 study. Eligible patients had advanced squamous-cell carcinoma, adenosquamous-cell carcinoma, or adenocarcinoma of the oesophagus refractory or intolerant to fluoropyrimidine-based, platinum-based, and taxane-based chemotherapy...
March 14, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28304223/metastatic-clival-chordoma-a-case-report-of-multiple-extraneural-metastases-following-resection-and-proton-beam-radiotherapy-in-a-5-year-old-boy
#20
Martin J Rutkowski, Harjus S Birk, Matthew D Wood, Arie Perry, Theodore Nicolaides, Christopher P Ames, Nalin Gupta
The authors report the case of a 5-year-old boy in whom extraneural metastases developed 5 years after he underwent an occipitocervical fusion and transoral approach to treat a clival chordoma without local recurrence. Following primary resection, the patient's postoperative course was complicated by recurrent meningitis secondary to CSF leak, which responded to antibiotics, and communicating hydrocephalus, for which a ventriculoperitoneal shunt was placed. The patient then underwent postoperative proton beam radiotherapy...
March 17, 2017: Journal of Neurosurgery. Pediatrics
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