Stage IV Non-Small Cell Lung Cancer


Stage IV non-small cell lung cancer (NSCLC)  is found in both lungs, in the fluid that surrounds the lungs or heart, or has spread to other parts of the body such as the liver, brain, or bones.

Although some patients with Stage IV NSCLC have cancer that has spread to only a single other site that can be treated with surgery or radiation therapy, chemotherapy is the mainstay of treatment for most patients with Stage IV NSCLC. Targeted therapies (which may be used in combination with chemotherapy) are also playing an important role in the treatment of selected patients with NSCLC.

Stage IV NSCLC is usually not considered curable, but treatment can prolong survival and reduce cancer symptoms.

About this NSCLC Treatment Information

The following is a general overview of treatment for stage IV NSCLC. Cancer treatment may consist of chemotherapy, targeted therapy, or a combination of these treatment techniques. Combining two or more of these treatment techniques has become an important approach for prolonging survival and increasing a patient's chance for cure.

In some cases, participation in a clinical trial utilizing new, innovative therapies may provide the most promising treatment.

Circumstances unique to each patient's situation influence which treatment or treatments are utilized. The potential benefits of multi-modality care, participation in a clinical trial, or standard treatment must be carefully balanced with the potential risks. The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.

  • Chemotherapy for Stage IV NSCLC
  • Targeted Therapy for Stage IV NSCLC
  • Maintenance Therapy
  • Treatment of the Elderly
  • Managing Bone Complications
  • Managing Brain Metastases
  • Managing Pleural Effusion
  • Strategies to Improve Treatment of Stage IV NSCLC

Chemotherapy for Stage IV NSCLC

Chemotherapy uses drugs that kill rapidly dividing cells, a hallmark of cancer. Cancer chemotherapy may consist of single drugs or combinations of drugs. It can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill.

Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread; it thus can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment.

Patients with advanced NSCLC are treated with chemotherapy to alleviate the symptoms of their disease and prolong their duration of survival. Research has shown that two-drug combinations improve survival over treatment with a single drug.

Targeted Therapy for Stage IV NSCLC

A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Targeted therapies are playing an increasing role in the treatment of NSCLC.

Avastin® (bevacizumab): Avastin is a type of targeted therapy that slows or stops the growth of blood vessels that deliver blood to the cancer, effectively starving the cancer of the oxygen and nutrients it requires to survive and grow. Avastin, in combination with the chemotherapy drugs paclitaxel and carboplatin, is FDA-approved for the treatment of advanced, non-squamous non-small cell lung cancer.

Xalkori™ (crizotinib): Up to 7% of non-small cell lung cancers have an abnormal version of the ALK gene that contributes to the growth and development of cancer cells. Xalkori is an oral medication that blocks certain proteins, including the protein produced by this abnormal gene. For advanced non-small cell lung cancers that test positive for the ALK gene mutation, Xalkori has produced very promising rates of response.1

Maintenance Therapy

Maintenance therapy refers to treatment that is given after initial treatment but before cancer progression. It is a relatively new approach to lung cancer treatment. Drugs that have been approved for maintenance therapy in selected patients include Alimta® (pemetrexed) and Tarceva® (erlotinib). For patients who are candidates for maintenance therapy, the approach has been shown to delay cancer progression and improve overall survival.2 3

Treatment of Elderly Patients

Many NSCLC cases occur in people over the age of 70, but there is limited information about how best to treat older patients. As a result of the limited information and concern that elderly patients will not be able to tolerate aggressive treatment, older patients may be treated with single-agent chemotherapy rather than the combination chemotherapy that is commonly used in younger patients. Studies have suggested, however, that although combination chemotherapy increases side effects, it also improves survival among elderly patients.4 Because relatively few studies have focused on older lung cancer patients, additional research on this issue is warranted.

Managing Bone Complications

NSCLC cells commonly spread to the bone, causing bone metastases. Bone metastases may cause pain, bone loss, increased risk of fractures, and a life-threatening condition characterized by a high level of calcium in the blood, called hypercalcemia.

Drugs that may be used to reduce the risk of complications from bone metastases include bisphosphonates such as Zometa® (zoledronic acid) and a newer type of bone drug, Xgeva® (denosumab).To learn more about bone metastases and bone health, go to the Bone Information Center.

Managing Brain Metastases

When NSCLC spreads to the brain, it can symptoms such as headaches and seizures. Depending on the number, size, and location of the tumors in the brain, treatment may involve radiation therapy and/or surgery to remove the tumor.

Managing Pleural Effusion

In some patients with advanced NSCLC, fluid collects in the space around the lungs. This is called pluerual effusion. The fluid can compress the lung and make it difficult to breath. If a patient is experiencing symptoms due to pleural effusion, the fluid may be drained using a catheter.

Strategies to Improve Treatment

The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. Future progress in the treatment of stage IV NSCLC will result from the continued evaluation of new treatments in clinical trials.

Patients may gain access to better treatments by participating in a clinical trial. Participation in a clinical trial also contributes to the cancer community’s understanding of optimal cancer care and may lead to better standard treatments. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. Areas of active investigation aimed at improving the treatment of stage IV NSCLC include the following:

New Approaches to Targeted Therapy: Researchers are continuing to evaluate new targeted therapies for the treatment of NSCLC. Tarceva, for example, which already plays a role in lung cancer maintenance therapy and second- and third-line lung cancer treatment, also appears to improve outcomes among newly diagnosed patients. Patient selection is important, however: studies in newly diagnosed patients suggest that the benefit of Tarceva is largely restricted to patients whose cancer has a mutation in the EGFR gene.5 Erbitux® (cetuximab) is another targeted therapy that has produced promising results in selected patients with NSCLC.6


1 Kwak EL, Bang Y-J, Camidge DR et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. New England Journal of Medicine. 2010;363:1693-1703.

2 Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009;374:1432-40

3 Cappuzzo F, Ciuleanu T, Stelmakh L et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncology. 2010;11:521-529.

4 Quoix E, Zalcman G, Oster J-P et al. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. The Lancet. Early online publication August 9, 2011.

5 Zhou C, Wu Y-L, Chen G et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomized, phase 3 study. Lancet Oncology. Early online publication July 22, 2011.

6 Pirker R, Pereira JR, Szczesna A et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009;373:1525-1531.