Looking at the Big Picture of Small Cell Lung Cancer

Small cell lung cancer is a unique type of lung cancer affecting 13% to 15% of all lung cancer cases, and treating the disease is based on if and how the cancer spread through the body, according to a presentation at CURE® Educated Patient® Lung Cancer Summit.

The presentation, given by Dr. Taofeek K. Owonikoko, professor and vice chair for faculty development in the department of hematology and medical oncology, leader of the thoracic oncology program and co-leader of the discovery and developmental therapeutics program at Emory University, also focused on potential advances in the treatment of small cell lung cancer, including reformulating existing therapies and focusing more on immunotherapy.

For patients with small cell lung cancer, the disease consists of very small cancer cells compared with the size of neighboring cells and blood cells. This differs from other types of lung cancer with cells that progressively increase in size, also known as non-small cell lung cancer. Although non-small cell lung cancer consists of several subtypes, small cell lung cancer is spoken about as a single disease, Owonikoko said.

Most patients who receive a diagnosis of small cell lung cancer have either used or were significantly exposed to tobacco, but there is a very small number of patients who did not have this type of tobacco exposure.

“Some of these could be patients who had preexisting non-small cell lung cancer with (an estimated glomerular filtration rate) that then transform into small cell (lung cancer),” Owonikoko said during the presentation. “Also, again, there could be de novo, newly diagnosis or newly developing small cell lung cancer patients who never used tobacco.”

Some symptoms that patients may experience before receiving a diagnosis of small cell lung cancer include coughing, weight loss, shortness of breath, pain or coughing up blood. Upon going to the doctor or the emergency room, if basic tests like blood tests and X-rays indicate something irregular in the lungs, patients will need to undergo a tissue biopsy from the lung or the surrounding lymph nodes.

“At the current time, we do not have any reliable blood tests that we can do to tell us that somebody has small cell lung cancer, … but that is a possibility for the future,” Owonikoko said. “A lot of efforts are now going into using blood-based samples to make that (diagnosis).”

Once a patient is diagnosed with small cell lung cancer, staging is recommended to quantify the amount of disease that is present, which will then guide treatment decisions. This is performed through CT scans, which can image lung tissue better than a chest X-ray. Other tests include a PET scan and MRI of the brain, which is the “gold standard to study the brain to see whether or not the cancer has gone there,” Owonikoko said.

Treatment decisions are based on the extent of the disease and how strong a patient is at that time. If a patient delays treatment for too long and are diagnosed later in the disease process, which may account for 20% to 30% of patients in the U.S., they may be too weak to undergo any type of treatment. If the disease is caught early and it is still limited to the chest, patients can undergo surgery to remove the affected area, especially if it’s not larger than 3 cm. This is particularly ideal if there is only a nodule in the lung and lymph nodes are not involved.

“In this part of the world, we don’t have that luck of catching this cancer when there’s no lymph node involved,” Owonikoko said. “I’ve only probably (seen that) in my career in less than 10 patients. In other parts of the world, where lung cancer screening is well established, people go through screening on a regular basis. They are now beginning to see small cell lung cancer also in the very early stage, what we call the very limited stage.”

After surgery, patients whose disease is caught early would also undergo chemotherapy. If a patient is not a candidate for surgery despite having limited disease in the chest, they will undergo chemotherapy with radiation usually over a six-week period.

If the cancer spread beyond the chest — also known as extensive stage disease — the disease may have affected both lungs or metastasized to the brain, liver, bones or another area outside of the chest. Surgery is not an option for these patients, so the main treatment approach is chemotherapy, which can benefit between 60% and 70% of patients. Chemotherapy has been the standard approach for these patients for almost 30 years, but in the past four years, immunotherapy has also been shown to be effective in the treatment of newly diagnosed patients with extensive-stage small cell lung cancer, particularly Tecentriq (atezolizumab) and Imfinzi (durvalumab).

“Either one of them combined with chemotherapy shows that, that approach is much better than chemotherapy alone,” Owonikoko said. “That will be the standard treatment as of today for somebody newly diagnosed with extensive-stage small cell lung cancer. Assuming they do not have any contraindication to going on immunotherapy, they should be offered that opportunity.”

Radiation to the brain may also play a role in treating patients to potentially prevent the appearance of cancer in the future. For example, prophylactic cranial irradiation may be used after completing radiation and chemotherapy to the chest when the disease is limited to the chest. If disease spread beyond the chest but doesn’t involve the brain, patients will need to discuss with their doctors the risks and benefits of this approach.

With small cell lung cancer, although patients may respond to initial treatment, approximately 70% of patients over time will have their cancer return. If it does come back, it becomes even more difficult to treatment, especially since there are limited options. Currently, there are two drugs approved by the Food and Drug Administration (FDA): Zepzelca (lurbinectedin) or Hycamtin (topotecan). Other chemotherapy can be used for these patients, although they have not been approved by the FDA. Sometimes the best approach for patients with recurrent disease is to participate in a clinical trial.

“I will suggest that if you have the option of going on a clinical trial, that would probably be a better approach to see if something better than just random chemotherapy would be of benefit,” Owonikoko said.

Several ongoing efforts are taking place in the clinical trial space including immunotherapy with new agents to target cancer cells and adding immunotherapy to chemotherapy and radiation to treat newly diagnosed patients with limited stage disease. In addition, researchers are assessing a new formulation of an existing chemotherapy called irinotecan to see if it’s easier to tolerate and more effective than its original formulation.

Research is also focused on new ways to divide small cell lung cancer into different categories as a way to facilitate treatments. This may allow for more targeted approaches to treatments instead of treating all patients with small cell lung cancer the same way.

“We still have to do the work before we can make that claim,” Owonikoko said.

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