How to Treat Melanoma: Current Landscape and Options
Today, melanoma is one of the most dangerous forms of skin cancer and late-stage melanoma accounts for the vast majority of skin cancer deaths. Following diagnosis, patients are often overwhelmed by the amount of information that is available to them regarding treatment options, therapy centers, and new terminology. The treatment landscape in melanoma is constantly evolving and scientists are finding safer and more effective treatments that have long term benefits for melanoma patients. To help summarize this information, the following is a brief overview of melanoma survival rates, treatment options, and new approaches. Survival Rate Survival rates for patients in the United States vary depending on the stage of cancer and when the patient is diagnosed. For early-stage melanoma (e.g., Stage I and/or II non-metastatic), surgical excision can be curative in a majority of cases. The overall five-year survival rate for patients with such localized melanoma is 98 percent in the United States.(1) At later stages, malignant melanoma remains deadly and difficult to treat cancer. The overall five-year survival rate is 63 percent in the United States when the cancer is detected in the lymph nodes; and, declines to 16 percent when the cancer has metastasized to distant organs. Treatment Options Melanoma that has metastasized to distant organs and tissues has traditionally been treated with a combination of surgery, chemotherapy and/or radiation therapy. Numerous chemotherapy regimens have been tested in melanoma with only modest success and limited overall survival benefit.(2) Immunotherapy, which harnesses the body’s immune system to fight cancer, has been an effective treatment for patients with certain types of cancer that have been previously resistant to chemotherapy and radiation treatment, such as melanoma. The emergence of two new approaches in immunotherapy – checkpoint inhibitors and targeted kinase inhibitors – have demonstrated improvement in overall survival of patients when compared to traditional chemotherapy.(2) While immunotherapy can be extremely effective, the currently marketed therapies do not benefit the majority of patients. While checkpoint therapies can produce durable responses, 70-80% of patients do not respond to this type of immunotherapy. This non-responder population represents a large unmet medical need in oncology. A New Approach Today, scientists are working on improving immunotherapies by combining them with other types of cancer treatments to improve response rates. This combination approach may increase the number of patients that can benefit from these revolutionary therapies. Early data from clinical trials evaluating these combination approaches are promising. Researchers also continue to focus efforts on targeting pathways of various immune cell activation.(3) One such approach relies on the correlation of a type of immune cell presence in a tumor with improved prognosis and long-term survival.(4,5) This cell type, known as a CD8+ T cell, is an immune cell that can recognize and kill cancer cells. Many emerging experimental immunotherapies are seeking to increase the anti-tumor CD8+ T cell response, resulting in increased immunogenicity of the tumor. Addressing the Unmet Medical Need OncoSec Medical Incorporated is developing combination approaches for melanoma and believes to be one step closer to providing an innovative immunotherapy option for patients. OncoSec is developing immune-stimulating therapies that can convert ‘T-cell poor’ (cold) tumors to ‘T-cell rich’ (hot) tumors by driving immune cells into the tumor and stimulating anti- cancer immune activity. By increasing T-cells at the tumor site, these therapies appear to prime the immune system for improved response to checkpoint inhibitors. In OncoSec’s Phase II investigational therapy trial, ImmunoPulse® IL-12 in combination with Merck's approved checkpoint inhibitor therapy, Keytruda® (also known as pembrolizumab), showed 48% of patients with advanced melanoma had a best overall response rate in patients with cold tumors. This is in comparison to a 33% response rate with KEYTRUDA alone, typically in patients that already have hot tumors. Based on previous positive clinical data, the US Food and Drug Administration (FDA), granted OncoSec Fast Track designation. Fast Track designation is an expedited review granted by the agency to facilitate the development of drugs which treat a serious or life-threatening condition and fill an unmet medical need. Based on this designation, OncoSec is initiating a registration- directed trial focusing on patients that fail on Keytruda®, Opdivo® or combination of Opdivo®- Yervoy®. This is a Phase II, open label, multicenter study of ImmunoPulse® IL-12 in combination with a checkpoint inhibitor therapy in patients with Stage III or IV melanoma that cannot be surgically removed. OncoSec is helping to pioneer combination approaches in the melanoma space and may be the first biopharma company to receive accelerated approval to help address the large population of patients who do not respond to current checkpoint inhibitor therapies. OncoSec is hoping to improve understanding of how different therapeutics can work better together to expand the number of safer and more effective combinations. It is the team’s goal to help improve outcomes for melanoma patients and provide hope for patients suffering from late-stage melanoma. Sources 1. American Cancer Society. Cancer Facts & Figures.2. National Cancer Institute. Melanoma Treatment for Health Professionals.3. Thomas, N. E., et al. (2013). "Tumor-infiltrating lymphocyte grade in primary melanomas is independently associated with melanoma-specific survival in the population-based genes, environment and melanoma study." J Clin Oncol 31(33): 4252-4259.4. Dudley, M. E., et al. (2005). "Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma." J Clin Oncol 23(10): 2346-2357.5. Hunder, N. N., et al. (2008). "Treatment of metastatic melanoma with autologous CD4+ T cells against NY- ESO-1." N Engl J Med 358(25): 2698-2703.
Immunotherapy: A New Era in Cancer Care
Immunotherapies harness the natural power of our immune system to target and fight disease. Advancements in science and technology have brought about a new wave of promising cancer immunotherapies. This burgeoning field of immuno-oncology (IO) is revolutionizing how we perceive and treat cancer.
Combining Therapies to Treat Cancer
There’s never been a more exciting time for the field of cancer immunotherapy. New treatments are showing great promise and changing the way we think about cancer care. At the forefront of this revolution is the idea of combining therapies to combat the many ways cancers can adapt and survive. As our understanding of cancer and the immune system grows, we are witnessing the emergence of a new vision – where practical combinations can benefit many more patients now faced with life-threatening disease. Immune Checkpoint InhibitorsThe Foundation of Immuno-oncologyCheckpoint inhibitors work by releasing the brakes on specialized immune cells, allowing them to target and eliminate cancer. These drugs can be highly effective, as evidenced by Jimmy Carter’s recent high-profile response. Unfortunately, at this point only a minority of patients are likely to respond to these breakthrough drugs. That’s where the power of combination therapy can make a huge impact… Data suggest patients with a ‘T-cell rich’ profile are likely to respond.Immune-stimulating therapies (like OncoSec’s ImmunoPulse IL-12) have shown an ability to convert ‘T-cell poor’ tumors to ‘T-cell rich’ tumors by stimulating anti-cancer immune activity.Combining new therapies with checkpoint inhibitors may increase the number of patients that can benefit from these game-changing drugs. Combination ApproachesThe Future of Cancer CareThe promise of combination therapy is forcing researchers and regulatory authorities to rethink how we approach cancer care. The era of single therapies competing for higher response rates is seemingly coming to an end. The focus is now shifting toward understanding how therapeutics work and evaluating how different approaches can work better together to improve outcomes for patients everywhere.
New Faces of Immunotherapy
Immunotherapy is changing cancer as we know it. Experts predict that in just 10 years, immunotherapy will form the backbone for over 60% of cancer treatments, as opposed to less than 3% today.
Cancer Moonshot 2020
Cancer Moonshot 2020 is a new initiative aimed to end cancer as we know it. Led by Vice President Joe Biden, Cancer Moonshot 2020 aims to break down barriers and enable progress by enhancing data access, facilitating collaborations, and investing in the development of new technologies and treatments. While the $1 billion announced to fund this initiative is a large figure on its own, the effort will need to hyper-focus its resources and influence to make a meaningful impact. In this issue, we explore some practical ways that Cancer Moonshot 2020 can make good on its promise to improve outcomes for patients everywhere. Early DetectionThe single most important factor for a patient’s prognosis is at what stage cancer is diagnosed. For example, the 5-year relative survival rate for breast cancer is 100% at Stage I and only 22% at Stage IV. However, at least half of all cancers in the U.S. are diagnosed in stage III or IV. Cancer Moonshot 2020 could improve early detection by investing in new technologies for early detection and screening. DevelopmentThe cost to develop a new cancer drug can range from $350 million to over $5 billion in some cases. Therefore, aiding the development of new therapies will take more than just money. Cancer Moonshot 2020 can best improve new drug development by influencing regulatory agencies like the FDA to rethink how we evaluate therapeutics. Experts believe patients will benefit most from combination therapies that target multiple aspects of cancer. Thus, regulatory agencies must learn to judge the value of therapeutic in both the single-agent and combination settings. CollaborationsThe battle between cancer and the immune system is a complex mix of activity and inhibition. Thus, the key to improving patient outcomes is to combine treatments that stimulate the immune system and limit the tumor’s ability to evade immune detection. Cancer Moonshot 2020 could help by breaking down barriers to collaboration and influencing regulatory agencies to favor combination therapies. Rational combinations, like the work coming from OncoSec Medical Incorporated, have the potential to change how we treat cancer. This initiative has the power to support these approaches and do a great deal of good.