Lung cancer is the most prevalent form of cancer on a global scale, and it stands as the primary cause of cancer-related deaths worldwide. A staggering 85% of lung cancer cases fall under the category of non-small cell lung cancer (NSCLC).
The landscape of treatment for early-stage NSCLC that is resectable is on the brink of significant transformation, thanks to promising outcomes from randomized trials that have assessed neoadjuvant and adjuvant immunotherapy, along with adjuvant targeted therapy.
Efforts by researchers are underway to enhance our comprehension of how to prevent, detect, and manage lung cancer. Notably, scientists have made headway in pinpointing numerous genetic mutations that can fuel the growth of lung cancer.
Early Detection of Lung Cancer
Numerous studies have been conducted to explore ways of detecting lung cancer at an early stage. Several techniques are currently under scrutiny to ascertain their potential in lowering the fatality rate linked to lung cancer.
CT Scan
The National Lung Screening Trial (NLST), sponsored by the NCI, demonstrated that low-dose CT scans are effective for screening lung cancer in individuals with a significant smoking history. The utilization of this screening method can reduce the likelihood of death from lung cancer. Currently, researchers are exploring methods to enhance CT screening for improved accuracy in detecting the presence of cancer.
Markers in Blood and Sputum
Researchers are currently working on enhancing tests for sputum and blood in order to detect lung cancer at an early stage. Two key areas of focus include:
- Investigating blood samples to determine if the detection of tumor cells or molecular markers in the blood can aid in the early diagnosis of lung cancer.
- Scrutinizing sputum samples for abnormal cells or molecular markers can pinpoint individuals who may require further follow-up.
Treatments for early-stage lung cancer
Early-stage lung cancer can frequently be addressed through surgical means. Scientists are working on developing methods to enhance the safety and efficacy of surgery.
- When lung cancer is detected early, individuals typically undergo surgery to remove an entire section (lobe) of the lung containing the tumor. However, recent clinical research has indicated that, for specific individuals with early-stage NSCLC, removing a portion of the affected lobe is equally effective as removing the entire lobe through surgery.
- The FDA approved the targeted therapy Osimertinib (Tagrisso) in 2021 for use as adjuvant therapy after surgery in individuals with early-stage NSCLC carrying certain mutations in the EGFR gene.
- Two immunotherapy medications, atezolizumab (Tecentriq) and pembrolizumab (Keytruda), have also received FDA approval for use as adjuvant treatments following surgery and chemotherapy in some early-stage NSCLC patients.
- Furthermore, the immunotherapy drug nivolumab (Opdivo) has been approved for use in combination with chemotherapy to treat early-stage lung cancer patients before surgery (neoadjuvant). This approval, granted in 2022, was based on the findings of the CheckMate 816 trial, which demonstrated that patients in this stage who received neoadjuvant nivolumab alongside chemotherapy had a longer lifespan compared to those who only received chemotherapy.
- In a separate trial (Keynote-671), early-stage NSCLC patients who received pembrolizumab in combination with chemotherapy before and after surgery showed improved outcomes compared to those who only received neoadjuvant or adjuvant treatment.
Treatments for advanced lung cancer
Cutting-edge treatments are now accessible for individuals diagnosed with advanced lung cancer. These mainly consist of immunotherapies and targeted therapies, both of which demonstrate ongoing benefits as scientific studies progress.
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Immunotherapy
Immunotherapies are a crucial component of current lung cancer treatment research, as they collaborate with the body’s immune system to combat cancer. Ongoing clinical trials are exploring novel combinations of immunotherapies, with or without chemotherapy, to effectively address lung cancer.
Immune checkpoint inhibitors, such as pembrolizumab (Keytruda), atezolizumab (Tecentriq), cemiplimab (Libtayo), durvalumab (Imfinzi), and nivolumab (Opdivo), are medications that disrupt the interaction between proteins on immune cells and cancer cells. This disruption ultimately reduces the immune response to the cancer, and several immune checkpoint inhibitors have already been approved for the treatment of advanced lung cancer.
Targeted Therapies
Targeted therapies are designed to pinpoint and combat specific cancer cells while minimizing damage to healthy cells. Over the past few years, numerous targeted treatments have emerged for advanced lung cancer, with additional options currently in the pipeline. Some of the targeted treatments for lung cancer are as follows.
Anaplastic lymphoma kinase (ALK) Inhibitors
ALK inhibitors are designed to target specific cancer-causing changes in the ALK protein. These medications are continuously being developed to better serve the 5% of NSCLC patients who possess an altered ALK gene. Among the approved treatments are ceritinib (Zykadia), alectinib (Alecensa), brigatinib (Alunbrig), and lorlatinib (Lorbrena).
These ALK inhibitors represent advancements over their predecessors due to their improved ability to penetrate the blood-brain barrier. This advancement is crucial because patients with non-small cell lung cancer and ALK mutations often experience disease progression in the brain. Following positive results from clinical trials, alectinib was granted FDA approval in 2024 as an adjuvant therapy for individuals with ALK-positive NSCLC.
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EGFR Inhibitors
EGFR inhibitors are medications that work by blocking the activity of a protein known as epidermal growth factor receptor (EGFR). In certain cases of lung cancer, altered forms of EGFR are present at elevated levels, leading to accelerated tumor growth. Osimertinib (Tagrisso) is recognized as the most effective and commonly used EGFR inhibitor, often utilized as adjuvant therapy following surgery for resectable NSCLC. Additional EGFR-targeting drugs approved for the treatment of NSCLC include afatinib (Gilotrif), dacomitinib (Vizimpro), erlotinib (Tarceva), and gefitinib (Iressa). Amivantamab (Rybrevant) is an approved targeted therapy specifically for individuals with Exon 20 mutations.
ROS1 Inhibitors
The ROS1 protein plays a crucial role in cell signaling and growth. A minority of individuals diagnosed with NSCLC exhibit rearranged versions of the ROS1 gene. Crizotinib (Xalkori) and entrectinib (Rozlytrek) are authorized therapies for individuals with these genetic alterations. In the latter part of 2023, repotrectinib (Augtyro) received FDA approval for the treatment of advanced or metastatic NSCLC with ROS1 fusions as a first-line therapy and as a second-line option for those who have previously undergone treatment with a ROS1-targeted medication.
BRAF Inhibitors
The B-Raf protein plays a crucial role in cellular signaling and growth. Alterations in the B-Raf gene can lead to enhanced proliferation and metastasis of NSCLC cells.
The drug dabrafenib (Tafinlar), which targets B-Raf, in combination with trametinib (Mekinist), targeting MEK protein, has received approval for treating NSCLC patients harboring specific mutations in the BRAF gene.
For patients with metastatic NSCLC carrying a BRAF V600E mutation, the combination of encorafenib (Braftovi) and binimetinib (Mektovi) has been approved as a treatment option.
Other Inhibitors
Certain NSCLCs carry mutations in the NRTK-1 and NRTK-2 genes, which can be effectively treated with targeted larotrectinib (Vitrakvi). Meanwhile, individuals with specific mutations in the MET gene can benefit from treatment with tepotinib (Tepmetko) or capmatinib (Tabrecta). Additionally, those with alterations in the RET gene can be treated with selpercatinib (Retevmo) and pralsetinib (Gavreto). A clinical trial conducted in 2023 demonstrated that treatment with selpercatinib resulted in longer progression-free survival compared to individuals who received chemotherapy with or without pembrolizumab. Furthermore, clinical trials are underway to test inhibitors targeting other drivers of certain lung cancers.
