The beginning of a new era
James Fleck: Anticancerweb 13(01),2020
Data from the American Cancer Society reported through 2016 revealed a disappointing 19% five-year survival rate for all patients diagnosed with lung cancer, further decreasing to just 5% for those with metastatic disease. Currently, molecular discrimination of non-small cell lung cancer (NSCLC) and program-death 1 ligand (PD-L1) tumor proportion score (TPS) have been identified as prognostic and predictive factors, leading to a consistent increase in advanced NSCLC survival rate. An unprecedent 38.5 months median overall survival was recently reported for EGFR-mutated advanced lung adenocarcinoma treated with osimertinib, a third generation EGFR tyrosine kinase inhibitor (TKI), hopefully defining a new standard of care (FLAURA trial). EGFR-mutation is identified in roughly 15% of US lung adenocarcinoma, increasing up to 65% in the Asian population. Although ALK (anaplastic lymphoma kinase) translocation is observed in only 4% of US lung adenocarcinoma, it also predicts a better response. In a recent retrospective review conducted at University of Colorado Cancer Center, the use of ALK-inhibitors in the primary treatment of stage IV ALK-positive NSCLC has been associated with a median overall survival of 6.8 years. ROS-1 rearrangements and BRAF mutation have also been described as predictive factors.
Fortunately, treatment advances have also been reported for advanced NSCLC patients who do not express driver mutations. Immune checkpoint inhibitors have been associated with an increase response rate and survival in treatment-naïve advanced NSCLC without EGFR/ALK alterations, particularly in those showing PD-L1 TPS ≥ 50%. In this selective group of patients, the use of pembrolizumab (a monoclonal antibody that binds programmed death-1 receptor, blocking its interaction with PD-L1 and PD-L2 and restoring the ability of the immune system to recognize tumor cells) has been associated to a five-year survival rate close to 30% (KEYNOTE 001). At the same time, the CHECKMATE 227 trial identified high tumor mutational burden (TMB ≥ 10 mutations/megabase) as a new predictive factor of response to the combination of nivolumab (humanized anti-PD1 IgG4 monoclonal antibody) + ipilimumab (humanized anti-CTLA-4 IgG1 monoclonal antibody). Predictive impact of TMB occurs regardless the percentage of PD-L1 expression. Despite immature data, the results indicate a potential benefit using predictive factors for a more personalized immunotherapy in non-small cell lung cancer. Additional efforts are coming from the use of new machine learning algorithms applied to the well-curated genomic data provided by The Cancer Genome Atlas in the identification of predictive markers.
References:
1. Rebecca L. Siegel, Kimberly D. Miller and Ahmedin Jemal, Cancer Statistics, 2019, Ca Cancer J Clin 69:7-34, 2019
2. S.S. Ramalingam, J. Vansteenkiste, D. Planchard, et al: Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC, N Engl J Med, Nov 21, 2019
3. Pacheco, JM, Gao D, Smith D, at al: Natural History and Factors Associated with Overall Survival in Stage IV ALK-Rearranged Non-Small Cell Lung Cancer, J Thorac Oncol 14 (4): 671-700, 2019
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Lung cancer has a major importance in oncology and medicine in general as being the third cancer site in incidence and the first one in mortality worldwide (it is actually the first in incidence also, among males). One big concern comes with the advance in gender equality: in the past, it was considered a men's disease, since it was very inappopriate for a woman to smoke, but now the statistics are getting more similar between men and women. It is of great importance the discover of new treatments and fortunately there are great results, especially in the immunotherapy field.
Considering lung cancer’s high incidence and mortality coupled to the dificulty in define patients to screening, the molecular discrimination constitute a promising method to prognosis avaliation and personalized therapy that can change global survival, progression-free survival and patient’s quality life. However, there is some barriers to the molecular discrimination’s establishiment at the clinical practice, as hight cost and lack of technological, especially in developing countries such as Brazil.
Knowing that lung cancer is one of the most prevalent and also has a high mortality rate, treatments such as immunotherapy come to our era as a hope for increasing the expectaction of life and patient's quality of life among oncology and pneumology. We also know that, even though there are a lot of government and health programs trying to make people think over tabagism, this habit is still a big global issue. For sure, these treatments are the future of oncology, but, for now, they are a distant reality in countries as Brazil, because of cost and acessibility.
Owing to the extremely low survival rates previously demonstrated, recent research showing some progress in treatment due to the administration of a more personalised immunotherapy comes as a breath of fresh air. Notwithstanding, we still have a long way to run.
Something that never ceases to amaze me is how much medical technology is advancing towards not only a personalized treatment, but also a personalized populational disease screening. The findings of this article shows us that the disappointing 19% five-year survival rate for all patients diagnosed with lung cancer is going to improve soon with pathology-specific drugs (like osimertinib, and many others), highlighting the importance of cancer-related medical research for society.
The improve and development of new treatments for lung carcinoma is of utter importance, due to its high incidence and mortality. Because of that, it amazes me to see how this area advances in terms of new specific therapies, especially with the advent of monoclonal drugs in the recent years.
The improve and development of new treatments for lung carcinoma is of utter importance, due to its high incidence and mortality. Because of that, it amazes me to see how this area advances in terms of new specific therapies, especially with the advent of monoclonal drugs in the recent years. I firmly believe that in the future years cancer will no longer be seen as a death sentence, but more like a chronic and highly treatable disease.
In a context of a disease such as lung cancer, with a five-year survival rate of 19% for all diagnosed patients and only 5% for those with metastatic disease, the emergence of new prognostic factors, which not only predict the risk, but also inform which treatment is best for each specific patient, in order to increase the survival rate, is very important. Therefore, additional efforts to identify predictive factors for a more personalized immunotherapy are very relevant to achieve good results in the treatment of lung cancer.
This disappointing survival rate for patient with lung cancer obviously draws the attention of the medical community: something has got to be done. Yes, we can use low dose computed tomography to screen lung cancer, but we need to be able to do more for the pacient. There are some specific mutations, predictive factors which we are seeing as the future of the treatment, and this is correlated to the "personalized medicine", bringing better survival rate.
We know that lung cancer has very discouraging numbers, with a high mortality rate and five-year survival rate of 19%, which is very low, and even worse for patients with metastatic disease, so the scientific community works hard to reverse and improve this numbers. The NSCLC and the TPS added an increase in the advanced NSCLC survival rate, although what turns out to be really promising on trying to balance the scale and significantly increase the numbers are the advances in personalized treatment, the identification of certain molecules infers the possibility of a differentiated targeted therapy for each mutation. These advances have a high beneficial potential, but as the cost is elevated, this form of treatment is not accessible to a specific part of the population. Which makes it more distant from the reality of developing countries.
The fact that researchers and other professionals are being capable of developing drugs directed to a specific mutation that is present in some patients' lung cancers is fantastic, because this is bringing more hope to the treatment of a disease that is highly prevalent and that has a really high - and sad - mortality rate associated. Although, thinking about the health system here in Brazil, I keep thinking that there will be two beginnings of new eras: the one that is about the developing of the new drugs which the text tells us about, and the other where these drugs will become something available in our system. Sadly, I think that this last one "new era" will take a few years longer to turn into reality, especially because these drugs - which are really new in the pharmaceutical market - are very expensive.
As shown in the text that in a selective group of patients, the use of pembrolizumab has been associated to a five-year survival rate close to 30% improving the 19% five- year rate survival, we are advancing little by little at giving a better life span and life quality to very a deadly form of cancer thus giving equally practitioners and pacients hope that oncology will no longer carry the stigma of "uncurable deseases".
Lung cancer is a worrying disease, since it has a high mortality rate. In addition, unfortunately, it is a cancer that, when diagnosed, is usually at a more advanced stage. With this in mind, it is phenomenal to develop a treatment based on immunotherapy for patients who express a specific type of mutation. The next step in this direction is to promote the democratization of access to this
Only about 15% of lung cancer patients discover the desease at a resectable stage. It is important to know that medicine has advanced in therapies that increase the survival, almost tripling it, of this cancer that has such a high and rapid mortality. We are waiting for more mature results.
Currently, treatments are being developed and tested for lung cancer treatment, such as immunotherapy and targeted drugs - medicine is getting more and more personalized. In this sense, we have an exponential growth of possibilities, it is necessary to use them in clinical practice in a more democratic way.
The development of new technologies in the treatment of cancer has resulted in remarkable changes in the prognosis of the disease. It is now possible to establish an individualized therapy based upon the unique molecular signature of each tumor, which results in greater success rates. Thus, it is vital that the scientific community engages in further research of this field, in order to enable a better quality of life for patients with cancer. Furthermore, it is also essential to guarantee that this new technology is universal and available to all.
This is an important finding because ALK-positive NSCLC is a subtype of lung cancer that accounts for approximately 5% of all cases, and historically, patients with advanced-stage disease have had poor prognoses. However, the introduction of ALK inhibitors has improved outcomes for this patient population. The study also found that ROS-1 rearrangements and BRAF mutation were predictive factors for response to ALK inhibitors. This information could be useful for identifying patients who are likely to benefit from this therapy.
Despite the reduction in the incidence of lung cancer, which is mostly a result of the reduction of the smoking habit in the previous decades, it continues to be the cancer disease with the higher mortality rates worldwide. Therefore, the advances in treatments for specific types of lung cancer are very encouraging, as they can lead to the cure and improved survival time of many patients. Nonetheless, efforts must also be made to create strategies that can improve the percentage of cases diagnosed in initial stages, as well to make sure that campaigns to discourage smoking are implemented with a focus on younger generations.
The recent development of monoclonal drugs for the treatment of lung cancer has brought new hope in the treatment of lung cancer, which still has high rates of prevalence and incidence. With the exponential growth of treatment possibilities, remarkable changes in the prognosis of the disease have been noted.
Os avanços tecnológicos para o tratamento do câncer de pulmão permitiram uma nova e animadora realidades para muitos pacientes. O desenvolvimento de drogas monoclonais pode possibilitar a cura, bem como um melhor prognóstico no tempo de sobrevida dos pacientes diagnosticados com câncer de pulmão, o que, anteriormente, não era uma realidade viável. Por meio dos avanços já alcançados, esse cenário passa por um transformação positiva e animadora.
In the past, lung cancer was often considered a death sentence, with low long-term survival rates, especially in advanced stages of the disease. The chronicity of lung cancer represents a significant advance in the fight against this devastating disease. While much remains to be done, continuing research, medical innovation and modern targeted therapies are bringing hope and substantial improvements to patients' lives, paving the way for a future where chronification can become a reality for an ever-increasing number. number of people affected by this disease.
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