Systemic Therapy for Stage IV Non-Small Cell Lung Cancer

August 31, 2015


To help doctors give their patients the best possible care, the American Society of Clinical Oncology (ASCO) developed evidence-based recommendations for the treatment of stage IV non-small cell lung cancer (NSCLC). This is lung cancer that has spread to other parts of the body. This guide for patients contains several recommendations updated in 2015 to reflect new research and treatment options.

Understanding systemic therapies for NSCLC

Systemic therapies are delivered through the bloodstream to reach cancer cells throughout the body. Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). Types of systemic therapies used for NSCLC include:

  • Chemotherapy. Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping the cancer cells’ ability to grow and divide.

  • Targeted therapy. Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells while limiting damage to healthy cells. There are genetic changes known to contribute to the growth of NSCLC on three specific genes: EGFR, ALK, and ROS1. Although there are genetic changes that occur on other genes, the current treatments approved by the U.S. Food and Drug Administration target genetic changes on these three genes.

Goal of treatment for stage IV NSCLC

The goal of systemic therapy for stage IV NSCLC is to keep the disease from growing and spreading. Patients must be prepared to have treatment on and off for the rest of their lives to control the disease. An important part of cancer care is relieving a person’s symptoms and side effects. It includes supporting the patient with his or her physical, emotional, and social needs. This type of care should be provided along with cancer treatment.

The first drug or combination of drugs a patient takes is called “first-line” treatment, which may be followed by “second-line” and “third-line” treatment. No specific treatment or combination of treatments works for every patient. If the first-line treatment causes unpleasant or dangerous side effects,  does not appear to be working, or stops working, the doctor may recommend a change in treatment.

During treatment, your doctor will monitor your progress in a variety of ways, including regular physical examinations, CT scans, PET scans, and blood tests. It is important that you tell your doctor about any symptoms you are experiencing.

Recommendations for systemic therapy for stage IV NSCLC

ASCO’s recommendations for systemic therapies for NSCLC are listed below. These recommendations depend on each patient’s health and his or her ability to perform daily tasks and functions, which is a measure called performance status. These recommendations also depend on the type of tissue where the cancer began and the results of testing.

First-line treatment recommendations

  • For patients with squamous cell carcinoma and nonsquamous cell carcinoma who do not have a genetic change on either the EGFR or ALK gene and who are mostly able to care for themselves, chemotherapy is recommended. The preferred chemotherapy is usually a combination of two drugs, one of which is platinum-based.

    • The targeted therapy bevacizumab (Avastin) may be added to chemotherapy if a patient is receiving a combination of carboplatin (Paraplatin) and paclitaxel (Taxol).

  • For patients with squamous cell and nonsquamous cell carcinoma who have a genetic change on the EGFR gene, the following targeted therapies may be options:

    • Afatinib (Gilotrif)

    • Erlotinib (Tarceva)

    • Gefitinib (Iressa)

  • For patients with a genetic change on the ALK or ROS1 gene, the targeted therapy crizotinib (Xalkori) is an option.

  • First-line chemotherapy should be stopped when the cancer worsens or if the disease has not improved after four cycles.

  • If first-line treatment includes the drug pemetrexed (Alimta), a patient may continue to take this drug if the cancer has not gotten worse during treatment. If first-line chemotherapy did not include pemetrexed, another type of chemotherapy or a break from chemotherapy may be recommended. However, pemetrexed may be used for nonsquamous cell carcinoma.

Second-line treatment recommendations

  • For patients with nonsquamous cell carcinoma, the following drugs are options:

    • Docetaxel (Docefrez, Taxotere)

    • Erlotinib

    • Gefitinib

    • Pemetrexed

  • For patients with squamous cell carcinoma, the following drugs are options:

    • Docetaxel

    • Erlotinib

    • Gefitinib

  • For patients with a genetic change to the EGFR gene, chemotherapy or a different targeted therapy is recommended if first-line treatment with targeted therapy did not control the cancer’s growth.

  • For patients with a genetic change to the ALK gene who had the cancer worsen after first-line crizotinib, chemotherapy or ceritinib (Zykadia) are options.

Third-line treatment recommendations

  • For patients who have not received erlotinib or gefitinib, erlotinib may be recommended.

  • Chemotherapy is not recommended.

  • Palliative care should be considered the major goal of third-line treatment, regardless of a patient’s choice of treatment.

  • Doctors and patients may consider other treatments, such as clinical trials or immunotherapy. Learn more about immunotherapy for NSCLC.

What This Means for Patients 

Systemic therapy for stage IV lung cancer may help lengthen and improve the quality of life for many patients with stage IV NSCLC. ASCO recommends different drug combinations based on a patient’s performance status, overall health, results of tumor tests, and previous treatments. A patient’s age should never be used as the only reason for deciding which treatment is best. It’s important that patients and their families talk with the doctor about the benefits and risks of chemotherapy to help them choose the care that will best help maintain or improve their quality of life. Many of these drugs cause different side effects and discussing the possible side effects of these treatments, both as single drugs and in combinations, and how to effectively manage or prevent any side effects can help patients make informed decisions about their care. Managing these side effects through palliative care is recommended throughout treatment.

If treatment is not successful in controlling the cancer’s growth, treatment may then focus on palliative care alone, without treatments intended to treat the cancer. This diagnosis is stressful, and it may be difficult to discuss. However, it is important to have open and honest conversations with your caregivers, doctors, and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Learn more about advanced cancer care.

Questions to Ask the Doctor

To learn more about your treatment options for stage IV NSCLC, consider asking your doctor the following questions:

  • What type of lung cancer do I have?

  • Am I a candidate for genetic testing and if so, what is the procedure for that?

  • What are my treatment options?

  • Which treatment do you recommend and why?

  • What clinical trials are open to me?

  • What is the goal of each treatment? Is it to eliminate the cancer, help me feel better, or both?

  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?

  • What are the names of the drugs, and how are they given?

  • What are the side effects of each drug?

  • What can be done to lessen these side effects?

  • Will some of the side effects end when the treatment ends? Will some last longer?

  • What palliative care services are available to me? Is there an integrative team to help me manage things like diet and daily activity in addition to other issues, such as mood swings, depression, rash, and hair loss?

  • How often will I need to visit the doctor to receive treatment, and how long will each visit take?

  • Will I be able to go to and return from this treatment on my own, or should I arrange to have assistance?

  • If I’m worried about managing the costs related to my cancer care, who can help me with these concerns?

  • What emotional support services are available to me? To my family?

  • Are there any other concerns or issues I should address at this time?

Helpful Links

Read the entire clinical practice guideline at

Guide to Lung Cancer

Making Decisions About Cancer Treatment


Personalized and Targeted Treatments