Small-cell lung cancer (SCLC) is a rare disease that affects 10% to 15% of people who get lung cancer. This year, for example, 229,000 people will be diagnosed with lung cancer, and about 34,000 of those will have SCLC.
It's a disease that is difficult to diagnose because it is often silent. That means SCLC causes no symptoms until the disease has evolved from the limited stage, which is still in one lung, to the extensive stage, where it has spread to other parts of the body.
Although the disease has been difficult to treat in the past, there are currently more than 2,000 active SCLC clinical trials. These treatments are in addition to the dozens of established and recently approved treatments available today.
"In the history of small-cell lung cancer, there has never been more on the horizon than there is today," says Christine Lovly, MD, PhD, division chief of thoracic medical oncology at City of Hope Cancer Center in Duarte, California. "There have been tremendous advances in research – laboratory research, clinical research – and outcomes that are reshaping this field right now. The enthusiasm and energy around research for small-cell lung cancer has never been greater."
Current Treatments for Small-Cell Lung Cancer
Today, if you are diagnosed with SCLC, your treatment will depend on if you've been diagnosed with limited-stage or extensive-stage cancer.
If you have limited-stage SCLC, the standard of care today is a treatment that includes chemotherapy called platinum-etoposide (EP) and radiation followed by immunotherapy, Lovly says. Patients are given either cisplatin or carboplatin along with etoposide. "That change – the immunotherapy after chemo and radiation – has only been a little over a year, and that's been a major, major, major, major advance to improve survival outcomes for patients with early-stage or what we call limited-stage SCLC."
Typical results from this combination are positive, with 70% to 80% of tumors shrinking after the treatment. Some limited-stage patients may also receive surgery to remove the tumors before starting treatment.
Once the treatment is complete and a patient's cancer hasn't progressed, they may go on an immunotherapy called durvalumab (Imfinzi).
Extensive-stage patients are treated with platinum-etoposide (EP) and radiation, too, and may receive prophylactic cranial irradiation (PCI) – radiation to the brain to kill any cancer that has spread but is too small to detect on imaging. Some patients may get chemotherapy with immunotherapy as a first-line option. Commonly used checkpoint inhibitors in SCLC include atezolizumab (Tecentriq) and durvalumab (Imfinzi).
If the cancer doesn't respond to the first-line drugs or it comes back after platinum chemotherapy, doctors move to tarlatamab (Imdelltra), a bispecific T-cell engager (BiTE) immunotherapy.
Other options after platinum-based treatment has failed include:
- Lurbinectedin (Zepzelca), a type of chemotherapy
- Topotecan (Hycamtin), a second-line chemotherapy option for relapsed SCLC
Treatments on the Horizon for Small-Cell Lung Cancer
For years, SCLC treatment was limited to a very small number of chemotherapy drugs and radiation. The addition of immunotherapy, which harnesses your own immune cells to fight cancer, has been groundbreaking. It's helping patients live longer and in some cases even find a cure.
The newest treatments scientists are focused on bringing to patients are called targeted treatment strategies. These strategies are designed to attack specific parts or features of cancer cells without damaging or killing your body's healthy cells. Features could include:
- Genes or gene mutations
- Proteins on the tumor's surface
- Signaling pathways – how the tumor replicates and grows
- Subtypes of the cancer
These include therapies that target DLL3 (a protein on certain cancer cells) such as:
- Next-generation T-cell engagers that get your own body's T cells to attack cancer cells that have overexpressed DLL3
- DLL3 antibody-drug conjugates (ADCs) that find a specific marker on the tumor and deliver a very potent chemotherapy, more precisely, to the tumor
Researchers are also looking at ADCs that target other proteins on the cancer cell. All of these treatments that use the immune system are especially promising, says Lovly.
"We have seen over and over and over and over again, in cancer medicine, that when we can harness the power of the patient's immune system to teach the immune system how to fight the cancer, the results can be profound and, more importantly, durable," she says.
Diagnosis: One Woman's Story
Maida Mangiameli, a 76-year-old woman who lives in a suburb of Chicago, was diagnosed with lung cancer almost accidentally. In 2018, she developed a cough that just wouldn't go away, she says.
"I started coughing, and it was incessant, so I went to an immediate care center. My first thought wasn't, 'Oh, I have lung cancer.' My first thought was, 'I've got some kind of infection.'"
The urgent care doctor she saw sent her for a chest X-ray. She was already getting chest X-rays every two years because of her history of smoking, and they had been clear. But this time, Mangiameli got bad news.
"The doctor who I would never see again called me and said, 'Make an appointment with your doctor. You have lung cancer.''"
Current Ways Small-Cell Lung Cancer Is Diagnosed
Mangiameli's experience is common. Right now, most people are diagnosed with lung cancer after getting imaging for what they think is a cough or pneumonia. Some people are diagnosed when having scans for other issues totally unrelated to their lungs. They may have headaches or other neurological symptoms, get imaging of their brain or another body part, and find cancer that has metastasized from the lungs. Either way, by the time SCLC is diagnosed, it is typically very large and has spread to other areas of the body, Lovly says.
"Sometimes, patients have a spot in the liver that is a lung cancer that has spread. And it's often a case that small-cell lung cancer is detected in an advanced stage where it has either spread from one lung to the other or to the lymph nodes or outside of the chest," she says.
When looking for lung cancer, doctors used imaging – usually PET scans, CT scans, or both, Lovly says. "And a biopsy is very important. Those pieces of information together give us the stage of the lung cancer."
Doctors want to find cancers before they have spread, so preventive scans are preferable. Today, for example, the United States Preventive Services Task Force has established guidelines recommending annual low-dose CT scans (LDCTs) for a specific population of people who are most at risk of getting the disease. This includes people between the ages of 50 and 80 years old who smoke and have at least a 20 pack-year smoking history. People who have quit smoking within the past 15 years who also have a 20 pack-year history also qualify. A pack-year is smoking an average of one pack a day for one year. If you smoke two packs a day for 10 years, you also qualify. Unfortunately, despite these guidelines, only about 6% of people who qualify for annual LDCTs get scanned.
Several studies have shown that receiving a yearly LDCT screening reduces all lung cancer mortality by between 20% and 24%. Although there can be instances of false-positive rates, experts believe the positives outweigh the negatives.
New Ways of Diagnosing Small-Cell Lung Cancer
Going forward, there are blood tests, which are also called liquid biopsies, that may eliminate the need for widespread LDCTs, but they are still years out. There are many companies and researchers working on the tests. One test, from the University of Kansas, uses activity-based enzyme biosensors to detect lung cancer, looking for changes in the blood that happen when cancer is present.
Another study, funded by the American Lung Association Research Institute's Lung Cancer Discovery Award, is being done in West Memphis, Arkansas. That blood test research, headed by Melinda Aldrich, PhD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, looks for cancer-linked DNA fragments in the bloodstream.
The most recent blood-based test uses a light-based sensor powered by CRISPR (a gene editing technology) to spot tiny amounts of cancer biomarkers in the blood.
Still, all these tests must go through FDA approval and peer review before they are available to the general public, Lovly says.
What New Treatments and Tests Mean
Patients having access to new tests and treatments will do two things, Lovly says. First, SCLC will be detected earlier, at limited stage, which makes it easier to treat and sometimes cure. What's more exciting, she says, is that the new treatments are becoming personalized, which has happened with other cancers, but has eluded researchers and doctors until recently.
"We're going to target small cells precisely, and we can target them in different ways," she says. "The innovation here is both in understanding the biology and finding these targets and in having these novel classes of drugs. There is tremendous hope that they will reshape this field entirely."
