Lung Cancer Treatment Options including Clinical Trials

Most lung cancers are treated based on the type of cancer cell, cancer stage, and cancer biomarkers. Lung cancer treatments also take into consideration the patient’s ability to do day-to-day activities, their health conditions, and medications. In addition to approved treatments for patients with lung cancer, new types of chemotherapies, immunotherapies, and targeted therapies are being investigated in clinical trials. The National Comprehensive Cancer Network (NCCN) recommends that patients, together with their treating physician, consider clinical trials as potential treatment options.

Lung cancer types

Non-small cell lung cancer (NSCLC) makes up about 80 to 85% of lung cancers. There has recently been an acceleration in lung cancer clinical research and approval of new treatments for NSCLC, with more than 15 new drugs FDA approved since the beginning of 2020. Within the NSCLC category, there are three main subtypes: lung adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. The names of these cancers come from the normal cells from which the cancer formed. Carcinomas are cancers of cells that are part of the lining of the inner or outer surfaces of the body.

About 10 to 15% of lung cancers are small cell lung cancer (SCLC) and these grow faster and spread faster than NSCLC. The US FDA recently approved a drug for SCLC patients on chemotherapy to reduce the side effects where blood cell production in the bone marrow is suppressed.

Lung cancer staging

Cancers are described in stages which indicate the extent of the cancer. When cancer spreads to other parts of the body it is called metastasis. Lung cancer may metastasize after diagnosis of stage 1, stage 2, or stage 3 lung cancer. Patients with stage 4 lung cancer have metastasis at diagnosis.

Metastatic lung cancer is unlikely to be cured with current treatments. Usually, local treatments such as surgery, radiation therapy, and chemoradiation are not used for metastatic lung cancer unless it has spread to a limited area that can be targeted.

The goals of treatments for metastatic lung cancer are to reduce symptoms, control the growth of tumor cells, and extend life. Metastatic lung cancer is usually treated with systemic treatments, treatments that affect the entire body and treat widespread metastasis. A recently FDA-approved chemotherapy drug for metastatic SCLC targets the DNA of these lung cancer cells, causing them to die or slow their growth.

Biomarker testing

In addition to differences in the cell type from which the cancer originated, abnormal changes at a molecular level may differ between patients. Biomarkers detect these molecular differences between cancers and are used to identify types of cancer that have a better chance of responding to certain treatments. For example, driver mutations and PD-L1 are biomarkers that suggest treatment with targeted therapy or immunotherapy respectively. More than one type of cancer may be included together in clinical trials involving cancer biomarkers as they may be shared by cancers that originate in different tissues or organs.

Treatment Options

Chemotherapy

Chemotherapy is a term for drugs that target and kill rapidly dividing cells. Some healthy rapidly dividing cells will also be killed by chemotherapy which is the reason for the side effects of chemotherapy. Treatment approaches may combine chemotherapy with other treatments.

Platinum-doublet chemotherapy uses drugs that contain platinum, cisplatin, or carboplatin, along with another type of chemotherapy. Platinum in the chemotherapy drug attaches and cross-links two strands of DNA together, which overwhelms the cell repair mechanisms and causes the damaged cells to destroy themselves. Immunotherapy may be combined with platinum-doublet chemotherapy.

Targeted therapy

Targeted therapy harms fewer normal cells than chemotherapy and is used to treat driver mutations. Driver mutations are changes to the genetic code that switch normal cells into cancer cells and are a type of biomarker. In lung cancer, a common driver mutation is a gene rearrangement or gene fusion. This is when parts of genes switch places and produce an abnormal protein that stimulates cancer growth.

Immunotherapy

Immunotherapy is a treatment that enhances the ability of the immune system to kill cancer cells. T cells in the immune system defend the body from infections and cancer. The immune system is controlled by immune checkpoints which are like “brakes” that slow down or prevent an immune response against the body’s healthy cells. One type of immune checkpoint is PD-1 a cell surface protein that is sort of a “brake pedal” on T cells. Some lung cancers have a protein called PD-L1 on their surface, which pushes that PD-1 brake pedal on T cells, turning down the cancer-killing activity. Immunotherapy uses checkpoint inhibitor drugs that prevent the interaction between PD-1 and PD-L1 so that T cells remain active against cancer. Alternate approaches to target these cell surface proteins or other target proteins in the immune response to cancer are either approved or are in clinical studies for lung cancer.

Clinical Trials

Clinical trials are medical research studies that take place after treatments are developed and tested in a laboratory setting. Clinical trials demonstrate safety and effectiveness in people before a treatment receives government approval. It is possible to access treatments before government approval by enrolling in a clinical trial. The NCCN recommends that patients consider clinical trials as potential treatment options.

Clinical trials are done in phases with each phase building on the previous one:

• Phase 1 trials study dose and evaluate the safety of the treatment
• Phase 2 trials study how well the treatment works for a specific type of cancer
• Phase 3 trials test the treatment compared to standard treatment and can result in government approval
• Phase 4 trials study the long-term safety and benefit of an approved treatment

The requirements for joining a clinical trial are called eligibility criteria and they ensure participants are similar in specific ways and that the trial is as safe as possible. These criteria are based on age, cancer type, and stage, treatment history, or general health. A clinical trial has a managing research team that reviews the study and provides details about the purpose of the study as well as the risks and benefits involved. Patients receive an informed consent form to read and are recommended to ask questions to the research team and discuss the clinical trial with their physician before making a decision.

Sometimes patients worry that they will receive a placebo or inactive version of the drug and miss out on treatment. However, placebos are rarely used alone in cancer clinical trials. Participants can expect to receive either an investigational drug a standard of care treatment or both. Patients may leave the clinical trial at any time if they wish to seek a different treatment.

New clinical trials are always becoming available. If a patient finds out about a clinical study, they should ask their doctor to check if the trial is suitable for them and if they are eligible. Patients should feel free to start a conversation with their doctor about clinical trials. This can help them consider all their treatment options, including those only available through clinical trials.

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