Ticiana Leal, MD, from the Winship Cancer Institute of Emory University, shared her insights during a discussion with Allen Wilbanks regarding the promising potential of TT fields (Tumor Treating Fields) as a treatment modality for cancer patients.
When asked about patient subgroups that might benefit more or less from TT field treatment, Dr. Leal responded with a wealth of knowledge and confidence. "I think, from the results of the Lunar trial," she began, "what we saw was a striking improvement in overall survival in the ICI-treated subgroups." She went on to elaborate, emphasizing the significance of combining immune checkpoint inhibitors (ICI) with TT fields. "In the ICI treated subgroups, the median overall survival was 18.5 months in the TT fields plus ICI versus 10.8 months in the ICI alone group with a hazard ratio here of 0.63 and a P value of 0.03."
Learn more by watching the full video.
Check the full interview with Ticiana Leal, MD here.
In this informative video, viewers will gain valuable insights into the groundbreaking research discussed by medical experts Ticiana Leal, MD, from the Winship Cancer Institute of Emory University, and Allen Wilbanks. The discussion revolves around the implications of recent findings for clinical practice in the field of oncology.
Dr. Ticiana Leal begins by highlighting the significance of the study, emphasizing its novelty in demonstrating an improvement in overall survival for patients who have previously undergone platinum-based chemotherapy and are now being treated with immune checkpoint inhibitors (ICIs) as a first-line therapy. She underscores the importance of these findings as a potential paradigm shift in cancer treatment.
Dr. Leal then introduces an innovative approach to cancer treatment known as tumor treating fields (TT fields), which is non-invasive and delivered through a wearable medical device. She elaborates on how this technology works, with electric fields being delivered to the tumors via two pairs of arrays applied to the patient's chest. The device, designed for continuous use for approximately 18 hours a day, is conveniently delivered to the patient's home and comes with 24/7 phone support by a device technician.
Furthermore, Dr. Leal discusses the potential synergy between TT fields and immune checkpoint inhibitors. She highlights that in their study, they observed a higher magnitude of benefit when combining these modalities, and this approach was well tolerated by patients. This combination therapy offers an exciting avenue for enhancing cancer treatment outcomes.
Dr. Leal concludes by pointing out the need for additional research to explore the integration of TT fields with immune checkpoint inhibitors in the front-line setting and in patients with locally advanced non-small cell lung cancer who have undergone chemo-radiation therapy. She emphasizes that ongoing clinical studies in these areas will provide further insights into how these results can impact clinical practice and ultimately benefit cancer patients.
Stay tuned for more updates on this promising and transformative approach to cancer treatment.
In a groundbreaking lunar trial, Ticiana Leal, MD, a distinguished expert from the Winship Cancer Institute of Emory University, spearheaded a Phase three study that promised to reshape the landscape of cancer treatment. This global, randomized study aimed to scrutinize the safety and efficacy of tumor treating fields (TT fields) therapy in conjunction with standard-of-care therapies. The subjects of this trial were patients grappling with advanced non-small cell lung cancer, a cohort that had experienced progression after undergoing platinum-based chemotherapy.
In a nutshell, the primary objective was to fathom the impact of TT fields therapy, either combined with an immune checkpoint inhibitor (ICI) or docetaxel, as opposed to administering these standard therapies alone. Patients were meticulously categorized based on their ECOG performance status and followed until disease progression or the emergence of intolerable side effects.
However, for the comprehensive and detailed findings of this groundbreaking lunar trial, viewers are encouraged to watch the video presentation by Dr. Ticiana Leal herself. The trial's key discovery, particularly the significant improvement in overall survival, unveils a promising avenue in the fight against advanced non-small cell lung cancer. So, don't miss the chance to delve into the intriguing insights presented in the video.
Watch HERE the full interview with Ticiana Leal, MD
Ticiana Leal, MD, is at the forefront of an intriguing and evolving discussion centered on the mechanism underlying tumor treating fields (TT fields). These fields are a topic of great interest in the field of oncology, and Dr. Leal's expertise shines through as she delves into the question at hand: how do tumor-treating fields actually work?
TT fields, a novel approach in cancer therapy, harness the power of electric fields to interact with electrically charged components within the human body, specifically targeting dividing cancer cells. Their precise mode of action revolves around disrupting the crucial process of mitosis, where cells divide and multiply. Dr. Leal and her colleagues explore this disruption in-depth, unraveling the intricate cellular events it triggers.
One key aspect they investigate is the induction of ploidy, an intriguing phenomenon where cells accumulate multiple sets of chromosomes due to TT field interference. This shift in cellular dynamics raises intriguing questions about the potential impact on cancer cell survival and behavior.
In a conversation hosted by Allen Wilbanks, Solange Peters, MD, PhD, a full professor and chair of medical oncology specializing in thoracic malignancies at the University Hospital of Lausanne in Switzerland, discussed the remarkable findings from the CheckMate 227 trial, particularly the six-year outcomes of Nivolumab and Ipilimumab as first-line treatment for metastatic non-small cell lung cancer.
Dr. Peters emphasized that Nivolumab and Ipilimumab, being chemotherapy-free, offer an intriguing approach based solely on immune responses. Another key aspect is that the treatment stops at two years, allowing researchers to evaluate the long-term effects of promoting an immune response.
Regarding the use of chemotherapy in combination with Nivolumab and Ipilimumab, Dr. Peters stated, "The feeling we have is chemotherapy does not add so much. So when you have this dual immunotherapy, provided that response is reached, I think the long-term benefit is really related to the immunotherapy part."
In summary, Dr. Solange Peters highlighted three key takeaways for oncologists:
In a discussion with Allen Wilbanks from Oncology Tube, Brandon McNaughton, CEO & Founder of Akadeum Life Sciences, shed light on the innovative Akadeum's human T cell activation and expansion kit and its impact on cell therapy. McNaughton explained the advantages of their microbubble-based technology compared to traditional methods, highlighting its gentleness, scalability, and compatibility with various cell culture systems.
He stated, "What's different about what we do, which is using tiny floating particles, we call them micro bubbles to essentially reach into a sample, essentially a blood bag that was derived from a phoresis or Luca pack. We use microbubbles to essentially grab onto, say, a T cell, which is something you use in CAR T therapy, and essentially float it to the top of a sample while everything else sinks. What that does, as you can imagine, it's the most gentle way, in our opinion, to recover a cell from a sample."
When asked about the economic and clinical benefits of incorporating Akadeum's technology into CAR T cell therapies, McNaughton discussed the potential to reduce costs through simplified processes and increased cell yield. He emphasized the importance of cost reduction in making cell therapies more accessible to patients.
Regarding the challenges of implementing Akadeum's technology, McNaughton acknowledged the need for increased awareness and the importance of demonstrating their product's effectiveness in the cell and gene therapy industry. He also emphasized the significance of providing support and guidance to researchers integrating their technology into their workflows.
In conclusion, Akadeum Life Sciences aims to make a meaningful impact on the field of cell therapy through their innovative microbubble-based technology, addressing challenges in cost, yield, and overall process efficiency.
In the pivotal phase 3 LUNAR study, Ticiana Leal, MD, and her colleagues made a groundbreaking discovery that could revolutionize the treatment of metastatic non-small-cell lung cancer (NSCLC) in patients who have experienced disease progression following platinum-based therapy. The study, which aimed to evaluate the efficacy and safety of TTFields therapy in combination with standard systemic therapy, yielded remarkable results.
Dr. Leal stated, "The randomized, pivotal phase 3 LUNAR study provides level 1 evidence that TTFields therapy, an innovative, locoregional treatment method, applied concomitantly with standard systemic therapy significantly improves overall survival in patients with metastatic non-small-cell lung cancer following progression on or after platinum-based therapy compared with standard systemic therapy alone."
The study's findings demonstrated that TTFields therapy not only extended overall survival by more than 3 months but also did so without exacerbating the toxicities commonly associated with systemic therapies. This is particularly significant in a landscape where treatment options are limited for patients with advanced NSCLC following progression on platinum-based therapy.
Dr. Leal continued, "Optimizing treatment after progression on platinum-based therapy remains an unmet need, particularly in the era of immune checkpoint inhibitors. In the LUNAR clinical study, overall survival was over 3 months longer with the addition of TTFields therapy, a clinically meaningful improvement that substantiates its use in this burdened patient population that has few other treatment options."
Moreover, the study demonstrated that TTFields therapy could be a valuable addition to immune checkpoint inhibitor therapy, yielding an impressive 8-month survival benefit in the subgroup receiving an immune checkpoint inhibitor. Preclinical models suggested that TTFields therapy could enhance the effectiveness of immune checkpoint inhibitors by inducing immunogenic cell death, ultimately improving patient outcomes.
However, it's important to note that the study had some limitations, including its open-label design and the relatively low number of patients with brain metastases, which may affect the generalizability of the findings to that population. Additionally, further research is needed to fully understand the relationship between TTFields therapy efficacy and tumor genetic subtypes.
In conclusion, the LUNAR study's results present a compelling case for the integration of TTFields therapy into the treatment landscape for metastatic NSCLC patients who have progressed after platinum-based therapy. This innovative locoregional approach has the potential to provide hope and improved outcomes for a patient population facing limited treatment options.
Check the full interview with Ticiana Leal, MD here
OneOncology, a rapidly expanding national platform for independent medical practices, proudly announces the completion of 25 distinctive oncology and hematology pathways. These pathways are now integrated into the platform's clinical decision support tool, a testament to OneOncology's dedication to precision and excellence. Lisa Sowinski-Raff PharmD, serving as Vice President of Pharmacy Services, plays a pivotal role in this achievement.
OneOncology adopts a physician-driven approach to pathway development, led by Medical Director Edward Arrowsmith, MD. Experts in gastrointestinal, genitourinary, breast, lung, and hematology, along with disease subject matter experts in gynecology and head and neck specialties, meticulously craft and continuously update these pathways. These pathways align seamlessly with nationally recognized, evidence-based guidelines, subject to regular review and refinement as new data emerges from recognized meetings and peer-reviewed journals.
The pathways are thoughtfully structured, categorizing treatment options by stage, including neoadjuvant, adjuvant, recurrent, locally advanced, and metastatic settings, with clear listings of potential treatment choices.
Davey Daniel, MD, Chief Medical Officer at OneOncology, emphasizes the program's significance within the diverse realm of cancer patients. The pathways address the multitude of clinical scenarios within each cancer type, highlighting clinical trial availability. The overarching goal is to simplify the ordering process for physicians and ensure prompt dissemination of the latest medical evidence.
Pathway development commences with rigorous review by the Pharmacy and Therapeutics (P&T) Committee, operating within OneCouncil—an all-physician governing body led by partner physicians within OneOncology. Approved drug monographs are then seamlessly integrated into relevant pathways, subject to further evaluation by the OneCouncil Disease Group, assessing the new agent's efficacy and adverse event profile compared to existing treatment options.
For Lisa Raff, Vice President of Pharmacy Services at OneOncology, efficacy and safety are paramount in the Pathways Program. Cost considerations come into play post-pathway approval. The overarching mission is to promote suitable first-line treatments rooted in genomic testing and biomarkers, alongside participation in value-based care programs. These pathways aim to minimize adverse events through standardized regimens and appropriate supportive care protocols.
In essence, OneOncology's commitment to precision and patient-centric care is embodied in these 25 unique oncology and hematology pathways. Under the leadership of Lisa Sowinski-Raff PharmD and the OneOncology team, these pathways set a new standard in cancer treatment, promising more effective and patient-centric strategies.
By: Timothy Looney, PhD
The topic at hand revolves around "Immune-Related Adverse Events (IRAEs)" in the context of cancer treatment using "Immune Checkpoint Inhibitors (ICIs)." Timothy Looney, a prominent researcher with a PhD, discusses the significance of IRAEs in cancer immunotherapy. IRAEs are adverse events that occur when therapeutic agents like ICIs activate T cells, causing them to mistakenly target healthy tissues, leading to damage or destruction. These events, which can range from mild to life-threatening, are a major concern in cancer immunotherapy due to the lack of effective predictive biomarkers.
The conversation also explores how T cell receptor beta variable (TRBV) gene polymorphisms influence T cell function and autoantigen recognition. Studying these polymorphisms in relation to IRAEs has historically been challenging due to the repetitive nature of TRBV genes and the presence of pseudogenes resembling them in the genome. Timothy Looney's research introduces a novel method, "long amplicon TCR beta chain sequencing," to accurately analyze TRBV polymorphisms in cancer immunotherapy patients. This approach identifies specific TRBV allele haplotypes associated with the risk of severe IRAEs, potentially transforming personalized cancer treatment.
The major findings of this study reveal a strong correlation between certain TRBV allele haplotypes and the risk of severe IRAEs. Patients can be categorized into different haplotype groups based on their TRBV allele profiles, allowing predictions about their likelihood of experiencing adverse events during immunotherapy. This breakthrough could revolutionize patient management and treatment strategies, offering personalized approaches to cancer care. Additionally, these findings have broader implications for autoimmune disease research, potentially aiding in the identification of predictive biomarkers for such conditions.
The interview with Jill O'Donnell-Tormey, PhD, delves into the vital topic of cancer immunotherapy and research, emphasizing the transformative potential of harnessing the human immune system to combat various forms of cancer. Throughout the conversation, O'Donnell-Tormey provides valuable insights and perspectives on key areas of focus within the field. Here are some direct quotes from her on these topics:
On the mission of the Cancer Research Institute (CRI):
"We are a non-profit organization that's been around for 70 years with the singular view that your immune system could be harnessed as a way to treat, control, and potentially cure all cancers."
On the impact of philanthropic donations:
"We rely on totally philanthropic donations to support our activities. We fund about 40 million a year in research that goes from the laboratory through translational through clinical trials."
On the significance of recent immunotherapy approvals by the U.S. FDA:
"Probably the most notable is that since the first time since 2014, a new checkpoint blockade. Antibody has been approved... I think this gives great hope that this is first seeing in melanoma, but we'll probably see this combination be approved in the years coming up in a variety of other cancers."
On the promising results of personalized neoantigen vaccines:
"So over the last year, we've seen two cases, one in basically advanced melanoma and in pancreatic cancer where these new personalized neoantigen vaccines... have been shown to have very promising results."
These quotes encapsulate the essence of the interview, which explores groundbreaking developments in cancer immunotherapy, the role of the Cancer Research Institute in advancing the field, and the potential of innovative technologies to shape the future of cancer care.
In the interview, Susan Pandya, MD, Vice President of Clinical Development at Servier Pharmaceuticals, discusses the pivotal FDA acceptance and priority review for TIBSOVO in the treatment of IDH1-mutated relapsed or refractory myelodysplastic syndromes (MDS). The acceptance marks a significant milestone in advancing targeted therapies for patients facing limited options in this challenging disease context.
TIBSOVO's clinical data submission showcased remarkable results, with complete remissions achieved in approximately 40% of patients and an overall response rate of 83.3% among those with relapsed or refractory IDH1-mutated MDS. These outcomes far exceed existing treatment options, underscoring TIBSOVO's potential as a transformative therapy for this patient population.
The potential approval of TIBSOVO as the first targeted therapy for IDH1-mutated MDS patients holds promise for improving their outcomes. It offers hope to the 3.6% of diagnosed patients who harbor this mutation and have historically faced limited treatment options, providing a pathway to enhanced survival rates and improved quality of life.
Marwan Fakih, MD - City of Hope - FDA Approval of LONSURF in combination with Bevacizumab
The FDA approval of Lonsurf plus Bevacizumab represents a significant breakthrough in the treatment of metastatic colorectal cancer. This combination therapy offers new hope for patients who have previously exhausted their treatment options, providing substantial improvements in both overall survival and progression-free survival.
The clinical trial results from the Sunlight trial have solidified Lonsurf plus Bevacizumab as the standard third-line treatment for metastatic colorectal cancer, with potential implications for future research and control arms in clinical trials. Physicians are encouraged to consider this combination for eligible patients and discuss its benefits and risks as it reshapes the treatment landscape in this challenging disease.
Can you provide an overview of the recent FDA approval of LONSURF® in combination with bevacizumab for the treatment of metastatic colorectal cancer (mCRC)? What are the key details about this approval?
How significant is the approval of LONSURF® plus bevacizumab for patients with metastatic colorectal cancer who have previously undergone fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy?
Could you explain the clinical trial design of the SUNLIGHT trial that led to this approval? What were the key endpoints and results of the trial?
The combination of LONSURF® plus bevacizumab showed statistically significant improvements in overall survival and progression-free survival compared to LONSURF alone. Could you discuss the magnitude of these improvements?
Were there any specific patient subgroups that particularly benefited from the combination treatment of LONSURF® and bevacizumab?
What were the most common adverse events associated with the combination of LONSURF® and bevacizumab in the SUNLIGHT trial? How manageable were these adverse events?
The approval covers patients previously treated with anti-VEGF biological therapy and, if RAS wild-type, anti-EGFR therapy. Could you explain the significance of RAS wild-type status in this context?
How does this FDA approval impact the current treatment landscape for metastatic colorectal cancer? Are there any other notable treatment options available?
Are there any specific considerations for patients with metastatic colorectal cancer who are considering treatment with LONSURF® plus bevacizumab?
What should physicians communicate to their patients?
What are the next steps for physicians now that LONSURF® plus bevacizumab has been approved? Are there any ongoing studies or initiatives related to this treatment?
Lajos Pusztai, MD, DPhil, Professor of Medicine, Co-Leader Genetics, Genomics, and Epigenetics Program, Scientific Co-Director of the Center for Breast Cancer, Yale Cancer Center. In this video, he speaks about the Cancer Relevance of Human Genes.
We postulate that genes that interact with core cancer genes (CCG) directly or indirectly in a comprehensive gene-gene interaction network may have functional value in cancer.
We classified 12,767 human genes into CCGs (n = 468), one (n = 5,467), two (n = 5,573), three (n = 915), and more than three (n = 416) steps distant from the next CCG in the STRING network. We estimated cancer-relevant functional importance in these neighborhood categories using I gene dependency score, which reflects a gene's effect on cell viability after knock-down; ii) somatic mutation frequency in The Cancer Genome Atlas, iii) effect size, which estimates the extent to which a gene mutation improves cell survival; and iv) negative selection pressure of germline protein-truncating variants in healthy populations.
The functional relevance of genes in cancer biology reduces as their distance from CCGs increases. Genes adjacent to cancer genes exhibit more network connectivity, are more important in sustaining cancer cell viability, are subject to more negative germline selection pressure, and have a higher somatic mutation frequency in cancer. We provide cancer relevance annotation to known human genes based on these four parameters.
A significant number of human genes are linked to core cancer genes and may influence cancer biology to varying degrees when dysregulated; any one mutation may be functionally important in one individual but not in another depending on genomic context.
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