Review
Oncology
Steven Nicolaides, Alex Boussioutas
Summary: Immunotherapy is an effective cancer treatment that activates the immune system to target and destroy cancer cells. However, the use of immune checkpoint inhibitors is often limited by immune-related adverse events. This review focuses on the management and emerging therapies for immune-related adverse events in the gastrointestinal system.
Review
Oncology
Xiao-Tong Zhang, Nan Ge, Zi-Jian Xiang, Tao Liu
Summary: This study evaluated the incidence of cardiotoxicity related to immune checkpoint inhibitor (ICI) therapies for lung cancer. The results showed that single ICI did not increase the risk of cardiotoxicity compared to chemotherapy, while single ICI plus chemotherapy increased the risk of cardiotoxicity by 67% compared to chemotherapy alone. Combination immunotherapy did not increase the risk of cardiotoxicity compared to single ICI.
CANCER CELL INTERNATIONAL
(2022)
Article
Oncology
Heidar J. Albandar, Jacob Fuqua, Jasim M. Albandar, Salahuddin Safi, Samuel A. Merrill, Patrick C. Ma
Summary: This study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.
Article
Endocrinology & Metabolism
Christopher A. Muir, Roderick J. Clifton-Bligh, Georgina Long, Richard A. Scolyer, Serigne N. Lo, Matteo S. Carlino, Venessa H. M. Tsang, Alexander M. Menzies
Summary: Thyroid dysfunction is common following immune checkpoint inhibition, with different subtypes of thyroid immune-related adverse events having unique clinical and biochemical associations. Overt thyrotoxicosis was associated with longer progression free survival and overall survival, while hypothyroidism showed no association with cancer outcomes. Multiple distinct phenotypes of thyroid irAEs suggest potentially different etiologies for thyrotoxicosis and hypothyroidism.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Endocrinology & Metabolism
Christopher A. Muir, Roderick J. Clifton-Bligh, Georgina V. Long, Richard A. Scolyer, Serigne N. Lo, Matteo S. Carlino, Venessa H. M. Tsang, Alexander M. Menzies
Summary: Thyroid dysfunction is common following immune checkpoint inhibition, with distinct phenotypes of thyroid irAEs showing unique clinical and biochemical associations. Overt thyrotoxicosis was associated with longer survival outcomes, while no association was found between hypothyroidism and cancer outcomes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Review
Immunology
Antonia M. Berz, Sarah Boughdad, Naik Vietti-Violi, Antonia Digklia, Clarisse Dromain, Vincent Dunet, Rafael Duran
Summary: Recently, cancer immunotherapies have seen significant development and have become crucial in treating various types of cancer. Immune checkpoint inhibitors have shown promise in improving patient outcomes, but they also come with the risk of immune-related adverse events (irAEs), affecting up to 76% of patients. These treatments commonly cause toxicities in the skin, gastrointestinal tract, and endocrine system. Computed tomography, magnetic resonance imaging, and 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography/computed tomography play key roles in detecting and characterizing these irAEs. It is important to differentiate irAEs from disease progression and other pathologies, such as infection or metastasis, and accurate imaging features characterization is crucial for timely and efficient patient management. F-18-FDG-PET/CT and radiomics have shown potential in reliably detecting these toxicities and predicting which patients are at risk of developing irAEs.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Li Zeng, Gang Ma, Kai Chen, Qiao Zhou
Summary: This study examined the trend of ICIs-associated rheumatic irAEs using bibliometric methods, finding that the United States is the leading contributor and observing shifts in research focus through keyword analysis and citation bursts.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Josefien W. Hommes, Rik J. Verheijden, Karijn P. M. Suijkerbuijk, Dorte Hamann
Summary: ICIs have improved cancer patient prognosis by blocking negative feedback mechanisms of the immune system, but can also lead to auto-immune toxicities. Despite numerous studies, no single biomarker has yet been proven to sufficiently predict the development of irAEs.
FRONTIERS IN ONCOLOGY
(2021)
Review
Radiology, Nuclear Medicine & Medical Imaging
Kathleen M. Capaccione, Jacienta P. Valiplackal, Alice Huang, Tina Roa, Alana Fruauff, Connie Liou, Eleanor Kim, Sakshi Khurana, Mary Maher, Hong Ma, Pamela Ngyuen, Serena Mak, Shifali Dumeer, Sonali Lala, Belinda D'souza, Sherelle Laifer-Narin, Elise Desperito, Carrie Ruzal-Shapiro, Mary M. Salvatore
Summary: Cancer immunotherapies modulate the body's immune system to enhance immune response against cancer. However, immune-related adverse events (IRAEs) can result from these therapies, making it crucial for radiologists to recognize and manage them effectively.
ACADEMIC RADIOLOGY
(2022)
Article
Oncology
Jae-Won Hyun, Ki Hoon Kim, Su-Hyun Kim, Ho Jin Kim
Summary: This study evaluated the occurrence and management of neuromuscular irAEs induced by ICIs at the National Cancer Center in Korea, and found that while rare, these irAEs can have devastating outcomes.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Immunology
Linyang Gan, Huan Chen, Xiaowei Liu, Li Zhang
Summary: This study investigated the incidence of immune-related adverse events (irAEs) of immune checkpoint inhibitor therapy and reported the clinical features, management, and outcomes of ophthalmic irAEs. Medical records of 962 patients who received ICI therapy were retrospectively reviewed, and 248 patients (25.8%) experienced irAEs. The first-year incidences of total irAEs and ophthalmic irAEs were 23.5% and 1.1% respectively. The most common ICI received was pembrolizumab (38.8%).
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Yuhong Wang, Chen Chen, Wei Du, Yixin Zhou, Lina He, Shaodong Hong, Li Zhang
Summary: This study evaluated the reporting quality of adverse events (AE), especially immune-related AE (irAE), in immunotherapy clinical trials. A total of 123 publications were included and assessed using a 16-point harm reporting quality score (HRQS). The findings showed that AE reporting in immunotherapy trials is suboptimal, highlighting the need for improvement and standardization of reporting practices.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Juyue Zhou, Zhonghai Du, Jie Fu, Xiuxiu Yi
Summary: Cancer research has focused on prolonging the life of patients, and immune checkpoint inhibitors (ICIs) have shown good clinical efficacy but with severe adverse effects. Blood counts may serve as predictors of immune-related adverse events (irAEs) in cancer patients. This meta-analysis provides further evidence for the importance of blood counts in clinical practice.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
David Hsiehchen, Abdul Rafeh Naqash, Magdalena Espinoza, Mitchell S. Von Itzstein, Alessio Cortellini, Biagio Ricciuti, Dwight H. Owen, Mehak Laharwal, Yukihiro Toi, Michael Burke, Yang Xie, David E. Gerber
Summary: The timing of immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI) varies greatly. Late-onset irAE is associated with better clinical outcomes compared to early-onset irAE.
Article
Oncology
Antonio Pizuorno Machado, Malek Shatila, Cynthia Liu, Jianbo Wang, Mehmet Altan, Hao Chi Zhang, Anusha Thomas, Yinghong Wang
Summary: This study aimed to investigate the characteristics of immune-related adverse events (irAEs) among patients with pre-existing autoimmune diseases (ADs) undergoing immune checkpoint inhibitor (ICI) therapy. The study found that patients with inflammatory bowel disease had the highest incidence of AD flare-ups, while patients with Hashimoto hypothyroidism and neurologic ADs had a higher incidence of new irAEs. Patients with pre-existing ADs experiencing flare-ups or new irAEs after ICI therapy tend to require aggressive immunosuppressive treatment.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
J. Randolph Hecht, Kyriakos P. Papadopoulos, Gerald S. Falchook, Manish R. Patel, Jeffrey R. Infante, Raid Aljumaily, Deborah J. Wong, Karen A. Autio, Zev A. Wainberg, Todd M. Bauer, Milind Javle, Shubham Pant, Johanna Bendell, Annie Hung, Navneet Ratti, Peter VanVlasselaer, Rakesh Verma, Joseph Leveque, Sujata Rao, Martin Oft, Aung Naing
Summary: The study demonstrated that pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC patients, with promising efficacy when used in combination therapy.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Oncology
Jeffrey A. How, Amir Jazaeri, Shannon N. Westin, Anil K. Sood, Lois M. Ramondetta, Mingxuan Xu, Abdulrahman Abonofal, Daniel D. Karp, Vivek Subbiah, Bettzy Stephen, Jordi A. Rodon, Fei Yang, Aung Naing
Summary: Treatment of recurrent, unresectable granulosa cell tumor of the ovary can be challenging, and there are currently no reports on the use of immune checkpoint inhibitors in GCT patients. However, a case series showed that some adult-type GCT patients treated with pembrolizumab experienced disease control for over 12 months with low toxicity, suggesting potential clinical benefit in this subset of patients. Further studies are needed to explore the role of immunotherapy in GCT and identify predictors of clinical benefit.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Oncology
Omar Alhalabi, Andrew W. Hahn, Pavlos Msaouel, Alexander Y. Andreev-Drakhlin, Funda Meric-Bernstam, Aung Naing, Sarina Piha-Paul, Janku Filip, Shubham Pant, Timothy A. Yap, David S. Hong, Siqing Fu, Daniel Karp, Erick Campbell, Hung Le, Matthew T. Campbell, Amishi Y. Shah, Nizar M. Tannir, Arlene O. Siefker-Radtke, Jianjun Gao, Jason Roszik, Vivek Subbiah
Summary: The prognosis for patients with metastatic bladder carcinoma (mBC) remains limited, but experimental therapies such as FGFR inhibitors have shown potential efficacy in disease control. Analysis of genetic alterations in TP53, ERBB2, PI3KCA, FGFR3, and ARID1A could help in selecting treatment options for patients.
MOLECULAR CANCER RESEARCH
(2021)
Article
Oncology
Aung Naing, Fiona Thistlethwaite, Elisabeth G. E. De Vries, Ferry A. L. M. Eskens, Nataliya Uboha, Patrick A. Ott, Patricia LoRusso, Javier Garcia-Corbacho, Valentina Boni, Johanna Bendell, Karen A. Autio, Manreet Randhawa, Greg Durm, Marta Gil-Martin, Mark Stroh, Alison L. Hannah, Hendrik-Tobias Arkenau, Alexander Spira
Summary: Probody therapeutics show potential safety and anti-tumor activity in the treatment of tumors, with low immune-related toxicity and signs of efficacy even in patients with low PD-L1 expression.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Oncology
Ryan C. Augustin, Robert D. Leone, Aung Naing, Lawrence Fong, Riyue Bao, Jason J. Luke
Summary: Evidence supports targeting the adenosine pathway in immuno-oncology, with clinical programs focusing on adenosine receptors and related factors. Intervening in the adenosine pathway can restore immune cell function and inhibit tumor growth.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Editorial Material
Oncology
Shubham Pant, Justin T. Moyers, Aung Naing
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Oncology
Aung Naing, John D. Powderly, John J. Nemunaitis, Jason J. Luke, Aaron S. Mansfield, Wells A. Messersmith, Solmaz Sahebjam, Patricia M. LoRusso, Ignacio Garrido-Laguna, Lance Leopold, Ryan Geschwindt, Kai Ding, Michael Smith, Jordan D. Berlin
Summary: This study evaluated the combination of Itacitinib with epacadostat or parsaclisib and found limited clinical activity or enhancement of immune activation in the tumor microenvironment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Gastroenterology & Hepatology
Hamzah Abu-Sbeih, David Szafron, Ahmed A. Elkafrawy, Victor Garcia-Rodriguez, Weijie Ma, Ann Xu, Shruti Khurana, Laith Numan, Ellie Chen, Ryan Goldstein, Adrianne Tsen, Yuanzun Peng, Mariela Blum, Edmund S. Kopetz, Naruhiko Ikoma, Malek Shatila, Wei Qiao, Gottumukkala S. Raju, William A. Ross, Phillip S. Ge, Emmanuel Coronel, Yinghong Wang
Summary: This study retrospectively reviewed the clinical characteristics, endoscopic findings, safety, and clinical outcomes of endoscopic interventions for gastrointestinal malignancy-related bleeding in patients at MD Anderson Cancer Center. The study found that endoscopy is a safe diagnostic tool, but endoscopic treatments may not decrease the risk of recurrent bleeding or improve survival.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Oncology
Aung Naing, Alain P. Algazi, Gerald S. Falchook, Benjamin C. Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B. Mettu, Pierre L. Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R. Patel
Summary: This study evaluated the safety and efficacy of the combination therapy of the IDO1 inhibitor epacadostat and the PD-L1 monoclonal antibody durvalumab in patients with advanced solid tumors. The study findings showed that the combination therapy had common adverse events and low objective response rate, and a higher dose of epacadostat was needed for sufficient drug effect.
Article
Oncology
Justin T. Moyers, Roberto Carmagnani Pestana, Jason Roszik, David S. Hong, Aung Naing, Siqing Fu, Sarina Piha-Paul, Timothy A. Yap, Daniel Karp, Jordi Rodon, Andy Livingston, Maria Alejandra Zarzour, Vinod Ravi, Shreyaskumar Patel, Robert S. Benjamin, Joseph Ludwig, Cynthia Herzog, Ravin Ratan, Neeta Somaiah, Anthony Conley, Richard Gorlick, Funda Meric-Bernstam, Vivek Subbiah
Summary: In this study, the outcomes of patients with ultrarare sarcomas in Phase 1 trials were assessed. The results showed that the median overall survival of ultrarare sarcomas was similar to common sarcomas, but the objective response rate to treatment was higher. Genomic selection played a significant role in identifying molecular subsets likely to benefit from targeted therapy in Phase 1 trials.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Henry Hiep Vo, Siqing Fu, David S. Hong, Daniel D. Karp, Sarina Piha-Paul, Vivek Subbiah, Filip Janku, Aung Naing, Timothy A. Yap, Jordi Rodon, Jaffer A. Ajani, Carrie Cartwright, Amber Johnson, I-Wen Song, Jennifer Beck, Michael Kahle, Graciela M. Nogueras-Gonzalez, Vincent Miller, Calvin Chao, David J. Vining, Donald A. Berry, Funda Meric-Bernstam, Apostolia-Maria Tsimberidou
Summary: The study investigated the challenges faced in conducting the IMPACT2 study in patients with metastatic cancer, revealing the complexity of executing randomized controlled trials in the field of precision oncology for advanced metastatic diseases.
NPJ PRECISION ONCOLOGY
(2022)
Article
Oncology
Blessie Elizabeth Nelson, Jason Roszik, Filip Janku, David S. Hong, Shumei Kato, Aung Naing, Sarina Piha-Paul, Siqing Fu, Apostolia Tsimberidou, Maria Cabanillas, Naifa Lamki Busaidy, Milind Javle, Lauren Averett Byers, John V. Heymach, Funda Meric-Bernstam, Vivek Subbiah
Summary: Combined BRAF + MEK inhibition has been approved by FDA for solid tumors with BRAF V600E mutation, except for colorectal cancer. However, besides MAPK-mediated resistance, there are other mechanisms of resistance, such as activation of CRAF, ARAF, MET, P13K/AKT/mTOR pathway. In the VEM-PLUS study, a pooled analysis of four phase one studies was conducted to evaluate the safety and efficacy of vemurafenib monotherapy and combination regimens in advanced solid tumors with BRAF V600 mutations. The results showed that compared to vemurafenib monotherapy, combinations of vemurafenib with targeted therapies or cytotoxic chemotherapy did not significantly improve overall survival (OS) or progression-free survival (PFS) of patients with BRAF V600E-mutant solid tumors.
NPJ PRECISION ONCOLOGY
(2023)
Review
Oncology
Omar Alhalabi, Roman Groisberg, Ralph Zinner, Andrew W. Hahn, Aung Naing, Shizhen Zhang, Apostolia M. Tsimberidou, Jordi Rodon, Siqing Fu, Timothy A. Yap, David S. Hong, Ming Sun, Yunfang Jiang, Shubham Pant, Amishi Y. Shah, Amado Zurita, Nizar M. Tannir, Raghunandan Vikram, Jason Roszik, Funda Meric-Bernstam, Vivek Subbiah
Summary: Pre-clinically, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinums and enhanced paclitaxel-induced cancer cell killing. In a clinical trial, patients with mTOR pathway aberrant tumors were treated with sapanisertib, carboplatin, and paclitaxel. The study showed that the combination therapy had manageable safety and preliminary antitumor activity in advanced malignancies with mTOR pathway alterations.
NPJ PRECISION ONCOLOGY
(2023)
Review
Oncology
Christian Rolfo, Elisa Giovannetti, Pablo Martinez, Shannon McCue, Aung Naing
Summary: Toll-like receptors (TLRs) play a crucial role in the immune system and have the potential to be targeted for cancer therapies. TLRs are involved in the defense against microbes and induce immune responses. By combining TLR agonists with immune checkpoint inhibitors, it is possible to convert cold tumors into hot tumors, improving treatment outcomes. Imiquimod is a TLR7 agonist approved for antiviral and skin cancer treatments, and several other TLR adjuvants are being used in vaccines. Many TLR agonists are currently being developed as monotherapy or in combination with immune checkpoint inhibitors for solid tumors.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Filip Janku, Divya Sakamuri, Shumei Kato, Helen J. Huang, S. Greg Call, Aung Naing, Veronica R. Holley, Sapna P. Patel, Rodabe N. Amaria, Gerald S. Falchook, Sarina A. Piha-Paul, Ralph G. Zinner, Apostolia M. Tsimberidou, David S. Hong, Funda Meric-Bernstam
Summary: The study found that combining vemurafenib with sorafenib or crizotinib could overcome therapeutic resistance in patients with BRAF mutations, and showed good tolerability and encouraging activity. Optional longitudinal collection of plasma to assess dynamic changes in circulating tumor DNA demonstrated the elimination of BRAF-mutant DNA from plasma during therapy (P = .005).