Non Small Cell Lung Cancer, NSCLC

About Non Small Cell Lung Cancer, NSCLC

Lung cancer develops in the lungs for many years. It is a leading cause in death by cancer in the US, Western countries.

The lungs are a double respiratory organ with a sponge-like texture and shaped like a cone in the chest. The lungs provide the body with oxygen and remove carbon dioxide from the body in the process of breathing.

For most patients with stage 4 metastatic lung cancer, current treatments are insufficiently effective. This gives rise to the need for innovative strategies with greater efficacy in fighting the disease.  The National Cancer Institute, NCI, highlights the fact that for a certain group of lung cancer patients, the best treatment option is to join one of the many clinical trials existing worldwide aiming to increase their chances of therapeutic success.

Types of Lung Cancer

We distinguish between two major types of lung cancer, when the distinction is based on the way the cells look under the microscope:

Non Small Cell Lung Cancer – NSCLC

This is the most common cancer and constitutes about 85% of lung cancers.

The disease develops in the lung tissue cells and a tight connection was found with smoking habits and history.

A persistent cough and shortness of breath are typical to patients with this disease and if a suspicion of cancer rises, the patient will undergo a biopsy.

The patients are classified by disease subtypes. In most cases of the disease, recovery is uncertain.

Small Cell Lung Cancer – SCLC

This cancer constitutes approx. 15% of lung cancers and is considered to be particularly aggressive.

Its source is in cells from the central region of the lung and connection was found with smoking habits and history.

This cancer spreads rapidly.

Types of Non Small Cell Lung Cancer, NSCLC,

3 Sub Types:

1. Adenocarcinoma

A malignant cancer that is the most common and constitutes approx. 50% of NSCLC.

Its source is in the glandular cells in charge of producing the lung mucus.

A link was found between adenocarcinoma and smoking; however, this type of lung cancer is common among non-smokers and among women.

A sub-type of adenocarcinoma is known as “Bronchoalveolar carcinoma”.

2. Squamous Cell Carcinoma

A malignant cancer which its source is in the cells coating the bronchi, and it usually spreads to the lung bronchi.

A link was found between squamous cell carcinoma and smoking and it is common among men compared to women.

Its rate of incidence is approx. 30% of NSCLC.

3. Large Cell, Anaplastic Carcinoma 

A malignant cancer that is not particularly common and its source is in the areas surrounding the lungs.

Causes of Non Small Cell Lung Cancer

The major cause of most lung cancer cases is active and passive smoking.

Other causes may be exposure to radon gas, asbestos, and lung cancer in a family member among other things; however, these are the minority of the cases.

Symptoms

Most lung cancer cases do not cause any symptoms to the patient, until the disease has spread and became metastatic. Nevertheless, some patients may suffer from lung cancer symptoms in earliest stages of the disease or be diagnosed with lung cancer by coincidence in an X-ray imaging.

In case one or more of the following symptoms are persistent, there is a suspicion of the disease occurrence.

• Ongoing cough or exacerbating cough
• Blood in the phlegm or rust color phlegm
• Chest pain which worsens with a deep breath, cough or laughter
• Hoarseness
• Loss of weight and loss of appetite
• Shortness of breath
• Fatigue or weakness
• Recurring infections such as bronchitis and pneumonia which do not clear out completely
• Wheezing while breathing
• Appearance of various syndromes such as Paraneoplastic syndromes and Horner syndrome among others

If the cancer is metastatic, meaning has metastasized to organs that are distant from the lungs, it might cause some of the following symptoms:

• Bone pain (such as pain in the back or the thighs)
• Changes in the nervous system, such as: headaches, weakness or     numbness of the arm or leg, dizziness, balancing issues or attacks
• Jaundice (yellowing of the skin and the white of the eyes)
• Appearance of lumps close to the body’s surface

Treatment Goals

In metastatic stage 4 disease, the primary objective of the treatment is to slow down and control disease progression and help reduce symptoms as well prolong life and improve patient’s quality of life.

The existing therapies used on stage 4 metastatic lung cancer are not curative. The National Cancer Institute, NCI, highlights the fact that for a certain group of lung cancer patients, the best treatment option is to join one of the many clinical trials existing worldwide aiming to increase their chances of therapeutic success.

Standard Treatments

A number of therapies are possible, and many patients shall receive more than one type of therapy

Surgery

There are two surgical options that are suitable to patients in stage 1 or stage 2:

• Radical Surgery

• Lobectomy Surgery

These surgeries target the removal of a lobe from the diseased lung or at times even removal of an entire lung with the goal not to harm the entire lung as well as the second lung, and preserve, as much as possible, the normal function of the lungs.

In case of stage 3 diseases, a surgery will be considered side by side with supportive care.

Patients in the metastatic stage – stage 4, are mostly defined as not-operable.
For the most part, before and after the surgery and recovery, patients will be started on supportive care.

Two main types of treatment may be offered to patients before and after surgery:

• Treatment prior to surgery is known as ‘Neoadjuvant’ 

Usually this stage of treatment will involve chemotherapy and/or radiotherapy intended to reduce the tumor’s size and improve the success of surgery.

• Post-surgery treatment, also known as ‘Adjuvant’ 

This treatment seeks to cure and prevent the appearance of metastases or recurrence of the tumor.

Radiotherapy

This involves use of radiation at higher levels of energy aims to kill the cancer cells remaining in the post-operative area.

Radiation may also cause decelerated growth of the localized tumor remaining in the area, or local recurrence.

In many cases, Neoadjuvant radiation will be used to shrink and reduce the tumor.

Chemotherapy

Chemotherapy is a medicated therapy which aims to shrink and erase cancerous cells and allow control over the disease.

Chemotherapy carries serious side effects, while its effectiveness is insufficient.

Chemotherapy’s impact has a range of side effects such as hair loss, loss of appetite, changes to bowel movements, fatigue, infection, hemorrhaging, incontinence, pain, and more.

Common chemotherapy treatments for lung cancer include

• Cisplatin, Carboplatin
• Alimta®, (Pemetrexed)
• Gemzar®, (Gemcitabine)
• Taxotere, (Docetaxel)
• Navelbine®, (Vinorelbine)
• Taxol®, (Paclitaxel)

Biological Treatments

Anti Angiogenesis

Cancer tumors survive and thrive in the body by causing the body to produce a system of blood vessels around them that nourishes them and provides them with oxygen.

Anti – angiogenesis agent is a biological antibody which harms the cancerous tumor capability to induce blood vessels growth around it from the environment where it is located, to nourish it so it continues to grow and proliferate.

In this way the tumor is “starved” to death.

Examples:

• Avastin® (Bevacizumab)
• Cyramza® (Ramucirumab)

Targeted therapies (per mutation or per protein)

A mutation is a change in the cell’s DNA sequence, the genetic code of the cell.

Mutations may occur when mistakes happen during the cell’s division process, or they may be caused by exposure to DNA harming agents such as free radicals, asbestos and others. At times healthy cells mutations may cause the generation of cancer in the body.

Anti EGFR

Common mutation in lung cancer. Prevalence among NSCLC –  ~ 20%

EGFR is a receptor on the surface of cells and helps the cells to grow and divide. Some NSCLC cells have much EGFR on the cells, which causes them to grow fast.

EGFR inhibitor drugs interfere the growing process of these cancerous cells.

Examples:

• Iressa® (Gefitinib)
• Giotrif® (Afatinib)
• Tarceva® (Erlotinib)
• Tagrisso® (Osimertinib) – patients with T790 mutation
• Portrazza® (Necitumumab) – for Squamous cell carcinoma patients

BRAF mutation

Mutations in the gene encoding for BRAF occur in many types of cancers and help tumors to grow and develop. Prevalence among NSCLC – ~ 5%

These drugs bind to this specific mutation and by that kill cancer cells in some patients.

• Tafinlar® (Dabrafenib)
• Mekinist® (Trametinib) – for patients with MEK Protein

ALK1 mutation

Prevalence among NSCLC – ~ 5% and adenocarcinoma

ALK is a protein found on blood vessels cells. In case of a cancerous cell this protein boosts the growth and proliferation of the cancer cell. Drugs used in the ALK 1 mechanism inhibit the formation of new blood vessels around the tumor in the cases where a mutation exists in the ALK protein. These drugs also act in the TKI (tyrosine kinase) inhibitors mechanism.

Examples:
• Alunbrig® (Brigatinib)
• Alecensa® (Alectinib)
• Zykadia® (Ceritinib)
• Xalkori® (Crizotinib)
• Lorbrena® (Lorlatinib)

Immunotherapy

Immunotherapy drugs assist the immune system in attacking the tumor. This type of treatment is very different from chemotherapy, for example, which directly attacks the cancerous cells but unfortunately also damages healthy tissues.

The immune system has “immune barriers” which serve to regulate the immune system and prevent it from attacking the body. In cancer these functions are readily activated and as a result, the immune system ceases to attack cancerous cells, enabling the tumor to grow and proliferate in the body.

Barriers known as PD-L1, PD-1 and CTLA-4 are found on T-cells and cancer cells. Immunotherapy is a revolutionary strategy, and one of the most widely studied worldwide for its application to numerous types of cancer and various stages of the disease’s development. Treatment is generally provided in the form of an intravenous infusion.

PD-1 Drugs

• Keytruda (Pembrolizumab)
• Opdivo (Nivolumab)

PD-L1 Drugs

• Tecentriq (Atezolizumab)
• Imfinzi (Durvalumab)

Advanced Cancer Drugs, Breakthrough Treatments and Clinical Trials from Around the World for Non Small Cell Lung Cancer

Facts

1. The existing therapies used on stage 4 metastatic lung cancer are not curative, and this is a source to the need for innovative and effective treatment strategies in order to fight the disease.
2. The National Cancer Institute, NCI, highlights the fact that for a certain group of lung cancer patients, the best treatment option is to join one of the many clinical trials existing worldwide aiming to increase their chances of therapeutic success.
3. Currently, every patient will be offered the standard protocols described above. Sometimes the oncologist may suggest integrating these therapies with trials carried out in the institute.

The Opportunity

1. Advances in cancer therapies may be found in clinical trials prescribing cutting edge, innovative drugs, some of which have already been recognized by the US Food & Drug Administration, the FDA, as “breakthrough drugs” and require further information to be approved.
2. An entire world of clinical trials, Compassionate drugs and advanced new cancer treatments are available worldwide.
3. It is important to know and have access to cutting edge cancer treatments that best match the unique medical condition of the patient and increase chances in winning the fight against compared to the standard care offered.

Note to remember!

Not every patient is eligible to enter a specific clinical trial. The eligibility conditions must be fully met and each case is reviewed separately to ensure that the clinical trial matches to the specific cancer patient and vice versa.

References:
ttps://www.fda.gov
https://www.ema.europa.eu
https://www.health.gov.il/Pages/HomePage.aspx
https://www.cancer.gov
https://www.cancer.org
https://www.cancerresearchuk.org
https://www.cancercenter.com

Dear Reader
This information is provided as a source of knowledge and does not constitute a medical consultation. For professional medical advice, see your attending physician. Information regarding drugs and commercial names belongs to the pharmaceutical companies