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Curative-Intent Treatment Improves Survival In Early NSCLC Regardless Of Race
Curative-intent therapy in patients with early non-small cell lung cancer resulted in "nearly identical survival" for Black and White individuals.
Curative-intent treatment for early-stage non-small cell lung cancer (NSCLC) yielded comparable survival rates in non-Hispanic Black and non-Hispanic White individuals, according to findings presented at the 2023 ASCO Annual Meeting.
"Racial disparities in early-stage NSCLC survival have persisted between [Black patients] and [White patients] in the past few decades," Paulo S. Pinheiro, PhD, and colleagues wrote. "The role of receipt of curative-intent surgery and/or stereotactic body radiation therapy (SBRT) in this disparity is unclear."
To investigate this question, Dr. Pinheiro and colleagues assessed associations of race/ethnicity and curative-intent treatment (surgery and/or SRBT) with mortality among individuals with early-stage NSCLC using population-based data from Florida, "the third largest state in the US and the second state in the number of cancer cases diagnosed annually," according to the study results.
The researchers examined all patients in the state with a diagnosis between 2007 and 2018 according to racial/ethnic group: non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander (API), and non-Hispanic White (NHW). Multivariable Cox proportional hazards regression models were used to examine the association of race/ethnicity and curative-intent treatment with lung cancer-specific mortality.
The analysis included data from 63,872 patients with early-stage NSCLC (83.2% NHW; 8.7% Hispanic; 6.6% NHB; 0.79% other races; and 0.77% API). Most patients (72.2%) received curative-intent therapy in the form of surgery or SRBT, or both. Median lung cancer-specific survival for all patients was 5.43 years.
After inclusion of all clinical and sociodemographic factors, such as stage at diagnosis and comorbidities, race/ethnicity (NHB vs NHW: HR, 1.06; 95% CI, 1.00-1.11) and curative-intent treatment (SBRT vs surgery: HR, 1.87; 95% CI, 1.78-1.97) were independently associated with lung cancer-specific mortality. However, after combining the effect of race/ethnicity and curative-intent treatment in the fully adjusted model, NHB patients who received curative-intent therapy had "nearly identical survival" compared with NHW patients (HR, 0.95; 95% CI, 0.87-1.03), according to the study results. Similar findings were seen in a competing risk analysis (subdistribution HR, 0.97; 95% CI, 0.89-1.02).
"The results underscore the importance of considering receipt of (specifically) curative-intent treatment rather than receipt of any form of surgery or radiotherapy in racial/ethnic survival disparities," Dr. Pinheiro and colleagues wrote. "The uptake of curative-intent surgery and SBRT, which currently stands at 56.5% and 9.4%, respectively, should be increased to improve survival outcomes for early-stage NSCLC for all."
DEBIOPHARM LAUNCHES PHASE 1 RESEARCH IN SMALL CELL LUNG CANCER WITH WEE1 INHIBITOR DEBIO 0123 TO OUTSMART DDR IN SMALL CELL LUNG CANCER
Debiopharm combines its potent WEE1-inhibitor Debio 0123 with standard-of-care therapy to short-circuit DNA damage repair (DDR) in adults with recurrent or progressive small cell lung cancer (SCLC).
The first patient dosed at Vall d'Hebron Hospital (Barcelona, Spain), was announced for this Phase 1 dose-escalation and expansion study evaluating Debio 0123 in combination with carboplatin and etoposide in participants with recurring or progressive, platinum-sensitive SCLC.
LAUSANNE, Switzerland, May 30, 2023 /PRNewswire/ -- Debiopharm (www.Debiopharm.Com), a privately-owned, Swiss-based biopharmaceutical company aiming to establish tomorrow's standard-of-care to cure cancer and infectious diseases, today announced the first patient dosed in its open-label, multicenter, Phase 1 study evaluating Debio 0123, an oral, potent, highly selective and brain penetrant WEE1 inhibitor, in combination with carboplatin and etoposide in patients with recurrent or progressive SCLC following standard platinum-based chemotherapy. This Phase 1 study, NCT05815160 (Debio 0123-SCLC-104), comprises two parts, namely a dose escalation phase to identify the recommended dose and an expansion phase, to characterize the safety, tolerability, and initial signal of antitumoral activity of Debio 0123 in combination with carboplatin and etoposide in this patient population.
SCLC is a highly aggressive, hard-to-treat cancer with poor prognosis, representing 15% of all lung cancers. It is characterized by an extraordinarily high proliferative rate, leading to early metastasis, most of which are already present at the time of diagnosis.1 Moreover, SCLC carries a massive variety of structural mutations and cell populations inside the tumor.1 This diversity in cell populations is known to play a critical role in tumor evolution, metastasis, and acquired resistance to available therapies. In the attempt to find new therapies, targeting the DDR pathway has shown great promise when combined with DNA-damaging agents such as carboplatin and etoposide.
The Debio 0123 program originates from a growing awareness of DDR inhibition in fighting life-threatening cancers. Optimizing efficacy, while preserving safety are key elements that Debiopharm is eager to assess throughout the clinical development of Debio 0123. With the fruition of these factors, Debio 0123 could become the first choice WEE1 inhibitor.
"Small cell lung cancer is the most aggressive type of lung cancer, and frequently presents with metastatic disease. Despite initial responses to front-line therapy these are typically transient, and survival at 5 years is infrequent. With this program we hope to show that Debio 0123 combined with one of the current standard of care treatments may extend the lives of recurrent small cell lung cancer patients." Dr. Luis Paz-Ares RodrÃguez, Coordinating Investigator.
"This combination might succeed in strategically enhancing antitumoral activity and delay the resistance to carboplatin and etoposide combination in patients with recurrent SCLC." expressed Dr. Esteban Rodrigo Imedio, Senior Medical Director, Oncology Research & Development, Debiopharm.
About Small Cell Lung Cancer (SCLC)
Lung cancer is the leading cause of cancer mortality worldwide with a yearly estimate of 250,000 new cases and 200,000 deaths globally.1 SCLC is most prevalent in men over 70 years of age, however the proportion of cases of women has risen over the past 50 years due to a popularization of tobacco consumption.1 SCLC, an aggressive high-grade malignant epithelial tumor, is deadly, highly metastatic, and highly mutagenic.1 Because of these traits and despite 30 years of clinical trials designed to improve therapies for SCLC, the outcomes for this disease still remain poor with a median overall survival from diagnosis of up to 13 months in patients receiving standard of care.2
About Debio 0123
Debio 0123 is a brain-penetrant, highly selective WEE1 kinase inhibitor. WEE1 is a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces an overload of DNA breaks. In conjunction with abrogation of other checkpoints such as G1, the compound pushes the cells through cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells. Currently in research for solid tumors in monotherapy and combination, Debio 0123 is being developed to respond to high unmet needs of patients living with the burden of difficult-to-treat cancers.
About DNA-Damage Repair (DDR)
When cells have damaged DNA, they need to undergo a repair process called DDR to be able to survive. Cancer cells use their hyperactive DDR response to divide and grow uncontrollably, which promotes cancer expansion. Inhibition of DDR, particularly in combination with other anticancer agents, induces an overall arrest in the uncontrollable cancer cell cycle. This ultimately activates a self-destruction program in cancer cells. DDR inhibitors such as Debiopharm's WEE1 and USP1 inhibitors, are being tested in clinical and preclinical studies.
Debiopharm's commitment to patients
Debiopharm aims to develop innovative therapies that target high unmet medical needs in oncology and bacterial infections. Bridging the gap between disruptive discovery products and real-world patient reach, we identify high-potential compounds and technologies for in-licensing, clinically demonstrate their safety and efficacy, and then select large pharmaceutical commercialization partners to maximize patient access globally.
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For more information, please visit www.Debiopharm.Com
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Debiopharm ContactDawn BonineHead of Communicationsdawn.Bonine@debiopharm.ComTel: +41 (0)21 321 01 11
References
[1] Rudin, C.M., Brambilla, E., Faivre-Finn, C. Et al. Small-cell lung cancer. Nat Rev Dis Primers 7, 3 (2021). Https://doi.Org/10.1038/s41572-020-00235-0
[2] Paz-Ares, Luis et al. "Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial." Lancet (London, England) vol. 394,10212 (2019): 1929-1939. Doi:10.1016/S0140-6736(19)32222-6
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What Is Non-Small Cell Lung Cancer?
© Provided by Verywell Health Edwin Tan / Getty Images Medically reviewed by Susan Russell, MD Lung cancer is an abnormal growth of cells in the lungs. These abnormal cells form tumors that damage the normal functioning of the lungs. Most lung cancer cases are non-small cell lung cancer (NSCLC), which can affect different types of cells in the lungs and airways.
Without treatment, non-small cell lung cancer can spread throughout the body, causing damage to other organ systems. This article will review the types of non-small cell lung cancer, how it is diagnosed, and its treatment options.
© Provided by Verywell Health Edwin Tan / Getty Images Types of Non-Small Cell Lung Cancer Non-small cell lung cancer makes up approximately 85% of all lung cancer cases. It is subdivided into three main types, depending on the type of cells that the cancer affects, as follows:
Symptoms of non-small cell lung cancer can relate to changes in your lungs, airways, and other body systems. Sometimes non-small cell lung cancer does not produce any noticeable signs and symptoms.
When asymptomatic, lung cancer may be detected through a chest X-ray if you have one done in diagnosing other conditions. For people at high risk (based on their age and smoking history), low-dose computed tomography (LDCT) imaging is now recommended for screening for lung cancer.
Early SignsEarly signs of non-small cell lung cancer, if present, often include shortness of breath and a cough that does not go away. The growth of cancer cells within the lungs and airways affects your ability to breathe, making it difficult to get air in and out of the lungs effectively. This can also result in:
As lung cancer spreads to other parts of the body, symptoms start to involve your entire body. You may experience such systemic symptoms as:
Non-Small Cell vs. Small Cell Lung CancerThe two main types of lung cancer are small cell lung cancer (SCLC) and non-small cell lung cancer. The main differences between the two are the size of the cancer cells when examined under a microscope.
As the names suggest, small cell lung cancer results from smaller cancer cells than non-small cell lung cancer. Small cell lung cancer tends to grow and spread more quickly, but non-small cell lung cancer is much more common.
Learn More: Small Cell vs. Non-Small Cell Lung Cancer: What's the Difference?
What Causes Non-Small Cell Lung Cancer?Anyone can develop non-small cell lung cancer, but it is much more likely to occur in smokers. Smoking significantly damages the lungs, causing inflammatory changes that can increase the risk of cancer cell growth.
Exposure to secondhand smoke, air pollution, radiation, toxic chemicals, dust, and fumes can also increase the risk of developing non-small cell lung cancer.
Sometimes, lung cancer has a genetic link in which gene mutations that cause lung cancer can be passed down through generations. If you have a family history of lung cancer, you may be at an increased risk of developing lung cancer.
How Is Non-Small Cell Lung Cancer Diagnosed?Non-small cell lung cancer is diagnosed through testing that examines the structure and function of your lungs. Diagnosis involves a variety of tests and procedures, which include:
As lung cancer continues to grow, it can progress through different stages. A higher stage of non-small cell lung cancer indicates that the cancer is worsening and spreading to other parts of the body. The stage of non-small cell lung cancer will influence what type of treatment is most appropriate.
The stages of non-small cell lung cancer include:
Treatment for non-small cell lung cancer will depend on the stage of cancer at diagnosis.
SurgerySurgical removal of a cancerous tumor from the lung is the first treatment option for early stages of non-small cell lung cancer, including stages 1 and 2 and stage 3A, when the cancer is well-isolated with minimal spread to other areas of the body.
For all other stages of non-small cell lung cancer, the tumor has spread too much to other areas, making surgery ineffective at removing enough of the cancer.
Radiation TherapyRadiation therapy, also called radiotherapy, involves exposing the areas of the body with cancer cells to targeted high-energy radiation beams. Radiation beams are powerful enough to damage the DNA within cancer cells to destroy them and stop them from dividing. Radiation therapy is often used together with chemotherapy to treat cancer.
ChemotherapyChemotherapy involves the use of powerful medications that kill rapidly growing cancer cells. Chemotherapy is often used for people with non-small cell lung cancer who are not eligible for immunotherapy treatment, especially if they have preexisting autoimmune conditions.
Chemotherapy and radiation therapy are typically the standard treatment for people with advanced non-small cell lung cancer (stages 3 to 4). Chemotherapy is often also administered after surgery to kill off any remaining cancer cells not removed from the body surgically.
ImmunotherapyImmunotherapy is a type of treatment that uses biologic medication to enhance the body's immune system to fight off cancer. Immunotherapy medications improve the function and activity of immune system cells so that they can better target cancer cells and stop or slow their growth.
Targeted TherapyTargeted therapy involves using medications that target the genes that cause cancer cells to form and divide. Approximately 10% to 30% of cases of non-small cell lung cancer are linked to mutations in the EGFR gene, while 5% or less of cases are linked to mutations in other genes, including the ALK, ROS1, RET, and BRAF V600E genes.
Ongoing research is geared toward developing drugs targeting these genetic mutations to stop abnormal cellular activity and decrease cancer growth and development.
Non-Small Cell Lung Cancer PrognosisUnfortunately, lung cancer has a poor prognosis, with a one-year survival rate of less than 50% and a five-year survival rate of less than 18%. Because lung cancer is not always symptomatic, almost 40% of people with it have already developed to stage 4 at the time they are diagnosed, making treatment less effective in slowing cancer growth.
Every case of lung cancer is different, however, and survival rates can vary from person to person depending on lifestyle factors and how early and aggressively treatment is administered after diagnosis.
Related: Lung Cancer Facts You Need to Know
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