Article
Multidisciplinary Sciences
Juliann Chmielecki, Jhanelle E. Gray, Ying Cheng, Yuichiro Ohe, Fumio Imamura, Byoung Chul Cho, Meng-Chih Lin, Margarita Majem, Riyaz Shah, Yuri Rukazenkov, Alexander Todd, Aleksandra Markovets, J. Carl Barrett, Ryan J. Hartmaier, Suresh S. Ramalingam
Summary: By sequencing circulating tumor DNA in patients from the FLAURA trial, this study identifies MET amplification and EGFR C797S mutation as the most frequent acquired resistance mechanisms to first-line osimertinib.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Luke S. McLean, Wasek Faisal, Sagun Parakh, Steven C. Kao, Craig R. Lewis, Melvin T. Chin, Mark Voskoboynik, Malinda J. Itchins, Ross R. Jennens, Adam R. Broad, Tessa A. Morris, Benjamin J. Solomon
Summary: This study focused on the outcomes of patients with EGFR-mutated non-small-cell lung cancer who developed leptomeningeal disease and were subsequently treated with osimertinib. The results indicated that osimertinib at a dose of 80 mg daily is an effective therapeutic option for these patients with limited treatment options.
JCO PRECISION ONCOLOGY
(2021)
Article
Pharmacology & Pharmacy
Tony S. Mok, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Alka Chawla, Rafael Rosell, Jesus Corral, Maria Rita Migliorino, Adam Pluzanski, Kay Noonan, Yiyun Tang, Malaika Pastel, Keith D. Wilner, Yi-Long Wu
Summary: This study provides an updated analysis of overall survival in patients with advanced NSCLC and EGFR-activating mutations treated with dacomitinib versus gefitinib. The OS benefit from first-line treatment with dacomitinib was maintained after extended follow-up, indicating its efficacy in this patient population.
Article
Oncology
Ciric To, Tyler S. Beyett, Jaebong Jang, William W. Feng, Magda Bahcall, Heidi M. Haikala, Bo H. Shin, David E. Heppner, Jaimin K. Rana, Brittaney A. Leeper, Kara M. Soroko, Michael J. Poitras, Prafulla C. Gokhale, Yoshihisa Kobayashi, Kamal Wahid, Kari J. Kurppa, Thomas W. Gero, Michael D. Cameron, Atsuko Ogino, Mierzhati Mushajiang, Chunxiao Xu, Yanxi Zhang, David A. Scott, Michael J. Eck, Nathanael S. Gray, Pasi A. Janne
Summary: Researchers have discovered a new EGFR inhibitor, JBJ-09-063, which shows efficacy against therapy-resistant mutations in EGFR-mutant lung cancer. The study also found that the resistance to JBJ-09-063 is caused by EGFR homo- or heterodimerization and specific mutations.
Article
Oncology
Chunsheng Wang, Kewei Zhao, Shanliang Hu, Wei Dong, Yan Gong, Conghua Xie
Summary: Both afatinib and osimertinib exhibited favorable clinical activities in patients with uncommon EGFR mutations. Afatinib showed a more profound and durable PFS benefit than osimertinib, although no efficacy advantage was observed.
Article
Oncology
Chunsheng Wang, Kewei Zhao, Shanliang Hu, Wei Dong, Yan Gong, Conghua Xie
Summary: This study compared the effectiveness of afatinib and osimertinib in patients with non-small cell lung cancer (NSCLC) with uncommon EGFR mutations. The results showed that afatinib had a better PFS benefit compared to osimertinib, but there was no significant difference in ORR between the two. For patients with non-ex20ins single uncommon EGFR mutations, the treatment outcomes were similar for afatinib and osimertinib.
Editorial Material
Oncology
Sun Min Lim, Chang Gon Kim, Byoung Chul Cho
Summary: Treatment resistance to targeted agents is a significant challenge in cancer therapy and is also observed in EGFR-mutant NSCLC. Current efforts focus on delaying or overcoming acquired resistance, and targeting compensatory feedback loops along with oncogenic signaling pathways holds promise for improved outcomes.
Article
Oncology
Masaki Kanazu, Masahide Mori, Madoka Kimura, Kazumi Nishino, Takayuki Shiroyama, Izumi Nagatomo, Shoichi Ihara, Kiyoshi Komuta, Hidekazu Suzuki, Tomonori Hirashima, Toru Kumagai, Fumio Imamura
Summary: The study found that both first- and second-generation EGFR-TKIs have favorable responses in NSCLC patients with uncommon EGFR mutations. Patients with G719X mutation had a more favorable progression-free survival compared to those with L861Q mutation and compound mutations. EGFR-TKIs not only present favorable responses but also contribute to long-term disease control in NSCLC patients with uncommon EGFR mutations, surpassing the effects of cytotoxic chemotherapy and immune checkpoint inhibitors.
Article
Pharmacology & Pharmacy
Xueting Cai, Jing Miao, Rongwei Sun, Sainan Wang, Miguel Angel Molina-Vila, Imane Chaib, Rafael Rosell, Peng Cao
Summary: Osimertinib-resistant EGFR-mutant NSCLC cell lines showed increased heme levels, while plasma heme levels were also elevated in patients treated with osimertinib. The antimalarial drug DHA was found to reverse osimertinib resistance by enhancing ROS levels and impairing heme metabolism. Combination treatment of osimertinib and DHA inhibited tumor growth and downregulated RTKs in a xenograft mouse model.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Oncology
Alexis B. Cortot, Anne Madroszyk, Etienne Giroux-Leprieur, Olivier Molinier, Elisabeth Quoix, Henri Berard, Josiane Otto, Isabelle Rault, Denis Moro-Sibilot, Judith Raimbourg, Elodie Amour, Franck Morin, Jose Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Aldo Renault, Eric Pichon, Benjamin Huret, Sandrine Charpentier, Marc G. Denis, Jacques Cadranel
Summary: The addition of cetuximab to afatinib in the treatment of treatment-naive advanced EGFR-mutant NSCLC did not show any significant improvement in efficacy, suggesting that further investigation into this combination therapy may not be warranted.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
K. Tamura, T. Yoshida, K. Masuda, Y. Matsumoto, Y. Shinno, Y. Okuma, Y. Goto, H. Horinouchi, N. Yamamoto, Y. Ohe
Summary: This retrospective study investigated the activity of EGFR-TKIs in untreated EGFR-mutated NSCLC patients with leptomeningeal metastases (LM). The results showed that osimertinib had better outcomes in LM compared to first-generation TKIs, especially in patients with exon 19 deletion.
Article
Oncology
Satoru Miura, Yasuhiro Koh, Koichi Azuma, Hiroshige Yoshioka, Kenichi Koyama, Shunsuke Teraoka, Hidenobu Ishii, Kayoko Kibata, Yuichi Ozawa, Takaaki Tokito, Jun Oyanagi, Toshio Shimokawa, Takayasu Kurata, Nobuyuki Yamamoto, Hiroshi Tanaka
Summary: The aim of this study was to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib. The maximum tolerated dose of afatinib when combined with osimertinib was determined as 30 mg, and the most frequent adverse events were diarrhea, anemia, and rash. The synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients.
Article
Chemistry, Medicinal
Meredith S. Eno, Jason D. Brubaker, John E. Campbell, Chris De Savi, Timothy J. Guzi, Brett D. Williams, Douglas Wilson, Kevin Wilson, Natasja Brooijmans, Joseph Kim, Aysegul Ozen, Emanuele Perola, John Hsieh, Victoria Brown, Kristina Fetalvero, Andrew Garner, Zhuo Zhang, Faith Stevison, Rich Woessner, Jatinder Singh, Yoav Timsit, Caitlin Kinkema, Clare Medendorp, Christopher Lee, Faris Albayya, Alena Zalutskaya, Stefanie Schalm, Thomas A. Dineen
Summary: While EGFR tyrosine kinase inhibitors have revolutionized the treatment of NSCLC, the development of resistance mutations remains a challenge. This study introduces a novel reversible inhibitor, BLU-945, that shows promising activity against different resistance mutations. Clinical trials are currently underway to evaluate its efficacy and safety.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Dongliang Bian, Liangdong Sun, Junjie Hu, Liang Duan, Haoran Xia, Xinsheng Zhu, Fenghuan Sun, Lele Zhang, Huansha Yu, Yicheng Xiong, Zhida Huang, Deping Zhao, Nan Song, Jie Yang, Xiao Bao, Wei Wu, Jie Huang, Wenxin He, Yuming Zhu, Gening Jiang, Peng Zhang
Summary: This study aimed to assess the feasibility of neoadjuvant Afatinib treatment for stage III NSCLC patients. The results showed that Afatinib improved the objective response rate (ORR) in NSCLC patients and caused dynamic changes in the tumor microenvironment.
NATURE COMMUNICATIONS
(2023)
Review
Oncology
Juan Bautista Blaquier, Sandra Ortiz-Cuaran, Biagio Ricciuti, Laura Mezquita, Andres Felipe Cardona, Gonzalo Recondo
Summary: The landscape of targeted therapies for EGFR-mutant NSCLC is expanding, but resistance to treatment is a challenge. Understanding and using DNA sequencing has led to the development of innovative strategies to overcome or prevent resistance in the clinical setting.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Luiz H. Araujo, Clarissa S. Baldotto, Mariana R. Monteiro, Pedro N. Aguiar, Maria Clara Andrade, Cecilia L. Longo, Mayara Batista, Raphaela Lima, Debora Azevedo, Natalia Carvalho, Perla Andrade, Mauro Zukin, Nelson Teich
Summary: This study explored patient-centered outcomes in lung cancer in a real-world setting, finding that patients diagnosed at advanced stages had more symptoms and lower functioning but tended to improve during treatment. The results demonstrate the feasibility of placing patients at the heart of cancer care and using their experiences to guide clinical approaches.
Article
Oncology
Guangsheng Zhu, Dian Ren, Xi Lei, Ruifeng Shi, Shuai Zhu, Ning Zhou, Lingling Zu, Ramon Andrade De Mello, Jun Chen, Song XU
Summary: The study found that FAT1 gene mutation may be a predictive biomarker for NSCLC patients with no durable clinical benefit to ICBs, and the established prognostic model performed well in screening NSCLC patients for ICBs.
Review
Oncology
Ramon Andrade de Mello, Giovanna Araujo Amaral, Nathalia Moises Neves, Estela Gudin Lippo, Fernanda Parini, Song Xu, Maria Tolia, Nikolaos Charalampakis, Hakaru Tadokoro, Pedro Castelo-Branco, Jinhui Zhu
Summary: Gastric cancer is the fourth most common type of cancer worldwide and the second most lethal. Gastric cancer biomarkers can be used for diagnosis, prediction of sensitivity to treatment, and prognosis. Some biomarkers can serve as therapeutic targets for antitumoral drugs.
Editorial Material
Immunology
Ramon Andrade de Mello, Giovanna Araujo Amaral, Carla Chizuru Tajima, Hakaru Tadokoro, Jairo Iavelberg, Debora Simonetti, Maria Tolia, Jose Antonio Silva
Meeting Abstract
Oncology
Laercio Lopes da Silva, Pedro Nazareth Aguiar, Renata D'Alpino, Rodrigo Dienstmann
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Oncology
Ramon Andrade Bezerra De Mello, Rafael Voscaboinik, Joao Vittor Pires Luciano, Rafaela Vilela Cremonese, Giovanna Araujo Amaral, Pedro Castelo-Branco, Georgios Antoniou
Summary: This paper provides a reliable data source on advanced non-small cell lung cancers without driver mutations and their treatment with immunotherapy. Through a review of the latest research on PD-1/PD-L1 and CTLA-4 inhibitors, the paper presents the current advancements in immunotherapy for this type of lung cancer, particularly the use of PD-1, PD-L1, and CTLA-4 inhibitors. Immunotherapy has transformed the treatment of advanced NSCLC lacking driver mutations, becoming first-line therapy with excellent results. The paper also explores the combination of cytotoxic chemotherapy, VEGF inhibitors, and immunotherapy for patients with low PDL-1 positivity tumors, showing significant improvement in overall survival and progression-free survival.
Article
Health Care Sciences & Services
Marina Kelner, Bruna Carvalho da Silva, Tatiane Montella, Pedro Nazareth Aguiar, Gilberto Lopes, Carlos G. Ferreira, Pedro De Marchi
Summary: This study compares the cost of treating advanced lung cancer in Brazil with the reimbursement provided by the Brazilian public healthcare system. It finds that the cost of the best treatment available is significantly higher than the amount reimbursed by the system.
VALUE IN HEALTH REGIONAL ISSUES
(2023)
Review
Pharmacology & Pharmacy
Pedro Nazareth Aguiar, Silvio Matsas, Rodrigo Dienstmann, Carlos Gil Ferreira
Summary: Personalized medicine has improved prevention and treatment of various types of neoplasms by providing individual-level knowledge. However, the high costs of genomic testing and targeted therapies are still a barrier, particularly in low- and middle-income countries. Efforts at a global level are needed to improve access to personalized medicine for more cancer patients.
PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Flavia Amaral Duarte, Pedro Nazareth Aguiar Junior, Rodrigo Dienstmann, Carlos Gil Ferreira
Summary: Precision medicine provides personalized interventions based on patients' or tumors' characteristics, but it faces challenges in becoming a global reality, with the main issue being inequities in access to genomic testing. Disparities exist between regions and populations, and socioeconomic factors play a significant role in this inequality.
EXPERT REVIEW OF PHARMACOECONOMICS & OUTCOMES RESEARCH
(2023)
Article
Oncology
Katia Roque, Rossana Ruiz, Iris Otoya-Fernandez, Jose Galarreta, Tatiana Vidaurre, Ramon Andrade de Mello, Silvia Neciosup, Luis Mas, Henry Gomez
Summary: This study retrospectively analyzed the use of telemedicine for cancer care during the COVID-19 pandemic. The results showed that telemedicine played an important role in maintaining the continuity of cancer care, and patients reported a high level of satisfaction with telemedicine.
Meeting Abstract
Oncology
Mirella Stival, Pedro Nazareth Aguiar, Marcos Aurelio Fonseca Magalhaes Filho, Auro Del Giglio
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, General & Internal
Daniela Pezzutti Domigues Armentano, Mariana Ribeiro Monteiro, Pedro Nazareth Aguiar, Jessica Sayuri Tsukamoto, Raquel Baptista Pio, Renata Arakelian, Raphael Leonardo Cunha Araujo, Pedro Luiz Serrano Uson Junior
Summary: This study aimed to investigate the association of red cell blood counts and liver panel tests with outcomes in patients with gastroenteropancreatic neuroendocrine tumors who underwent systemic antineoplastic treatments. Laboratory tests were conducted, and the results showed that chromogranin A, neutrophils, and platelets-to-lymphocyte ratio were associated with disease progression.
EINSTEIN-SAO PAULO
(2022)
Article
Medicine, General & Internal
Marcos Aurelio Fonseca Magalhaes Filho, Pedro Nazareth Aguiar, Milena Brachmans Mascarenhas Neves, Gilberto de Lima Lopes, Auro del Giglio
Summary: This study compared the treatment effectiveness and cost-effectiveness of T-DM1 and trastuzumab for residual invasive HER2-positive breast cancer. The results showed that T-DM1 had better invasive disease-free survival and overall survival compared to trastuzumab, and it was cost-effective from both Brazilian and American perspectives.
EINSTEIN-SAO PAULO
(2022)
Article
Immunology
Geane Tomaides Henriques, Cleide Barbieri de Souza, Pedro Nazareth Aguiar
Summary: Currently, immunotherapy based on immune checkpoint inhibitors is a crucial treatment option for non-small-cell lung cancer. However, not all patients respond well to this therapy, and the available biomarker (PD-L1 expression) has limitations. Understanding the tumor genetics and microenvironment could provide potential tools for patient selection and the development of new predictive biomarkers.
Article
Oncology
Helder Almeida-Lousada, Andre Mestre, Sara Ramalhete, Aryeh J. Price, Ramon Andrade de Mello, Ana D. Marreiros, Ricardo Pires das Neves, Pedro Castelo-Branco
Summary: Colorectal cancer plays a significant role in cancer incidence and mortality worldwide, requiring improved screening methods for early detection and patient management. The three pillars of CRC screening include endoscopy, radiological imaging, and molecular assays, with biomarker-based screening methods showing promising advantages for the future.
