When you’re living with extensive-stage small-cell lung cancer (ES-SCLC), your first treatment to slow the disease from worsening may be pretty different from your second. One key thing to know is that the options for both lines of treatment have flourished in recent years.
“I think it’s really important for any patient who’s diagnosed with small-cell lung cancer [and] any family members…to be aware of the reasons for optimism in this disease,” says Carl M. Gay, MD, PhD, deputy director of clinical research in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston.
Most people with SCLC are diagnosed with the extensive-stage type. That means the disease has spread widely throughout your lung, to your other lung, or to distant parts of your body. There’s no cure. And for decades, chemotherapy was the top FDA-approved treatment to slow the disease; the outlook then was bleak.
Today, immunotherapy drugs that have been approved, and promising experimental medications available through clinical trials are, along with chemo, helping more people live longer and better.
Learn about the main first- and second-line treatment options for ES-SCLC here. Plus, find out why it’s never too early to get palliative care, what types of experimental treatments are showing promise, and when to ask for a second opinion.
First-Line Treatment Options for ES-SCLC
If you’re otherwise healthy and your goal is to try to slow the ES-SCLC from spreading more, your cancer doctor (oncologist) will likely suggest that you try chemotherapy and immunotherapy first. Chemo uses drugs to destroy cancer cells throughout your body. Immunotherapy uses substances made by your body or in a lab to help your body’s defenses (immune system) seek and attack cancer cells.
If you’re otherwise unhealthy and you want to try to slow ES-SCLC from spreading more, your oncologist may suggest that you get lower doses of chemo without immunotherapy. That could help minimize treatment side effects that might take a further toll on your overall health.
Chemo and immunotherapy drugs
For chemo, oncologists often use carboplatin or cisplatin (aka “platinum drugs” that destroy cancer cell DNA) along with etoposide (Avopef, VePesid) or irinotecan (Camptosar). The combo of carboplatin with etoposide is especially common with ES-SCLC. “In the extensive-stage setting, we almost always use carboplatin because it does have a better toxicity [side effect] profile,” says Christine Hann, MD, PhD, a medical oncologist at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore.
The immunotherapy drug that’s added to the chemo is usually either atezolizumab (Tecentriq) or durvalumab (Imfinzi). Both of these drugs are also known as checkpoint inhibitors or PD-L1 immunotherapy. They work by “waking the immune system up to recognize the enemy that’s been hiding in plain sight in front of it,” since cancers are good at cloaking themselves from your body’s defenses, Gay says.
Before the FDA approved atezolizumab or durvalumab for use with chemo, randomized study results on the drug combo marked “one of the first times that we had seen patients that had metastatic extensive-stage small-cell lung cancer have the potential for long-term survival and long-term remissions,” he says. “That potential was low, but previously [it] had been essentially nonexistent.”
Supportive (palliative) care
You can ask for this added layer of health care at any time — even as soon as you’re diagnosed with ES-SCLC, whether you’re otherwise healthy or not. A palliative care team can ease cancer symptoms and treatment side effects, connect you with mental health care if needed, and offer other helpful services. It’s different from end-of-life hospice care.
Some data show that starting palliative care early on helps people live longer and do better, says Isabel Preeshagul, DO, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center in New York. “I often say, I have my symptom care team. And their goal is to address your symptoms and make sure that you feel as good as you can while you’re on treatment or if you were to ever stop treatment. They wear many different hats,” she says. “They’re not going to push hospice on you by any means.”
Side effects of first-line treatment
With chemotherapy, the most common side effects of carboplatin plus etoposide that you might notice are fatigue, changes in taste and smell, and hair loss, Hann says.
The fatigue waxes and wanes. Most people will have it around the middle of a three-week chemo cycle, Hann says. She encourages her patients to try to get enough nutrition and sleep and be as active as they can handle to offset the severe tiredness. Also, “take that extra nap. Kind of lean into it. Don’t try to overcompensate for being fatigued, because it’s natural,” she says.
If your food starts to taste or smell different, it could make you less interested in eating. Your favorite foods may become less appetizing, and things you used to dislike may become more palatable. Hann recommends trying various foods during this time. Changes in taste and smell usually go away once you finish getting chemo, she says.
If the possibility of hair loss concerns you, you can ask your care team if scalp cooling devices or cold caps might help prevent it. These items aren’t recommended for everyone, though. They can cause side effects of their own. You could also think about buying a wig or other head covering; ask your health insurer if your plan covers any of the cost.
If you have an upset stomach during treatment, be sure to ask for anti-nausea medicine. Hann says these meds are quite effective.
With immunotherapy, diarrhea or rash are the two most common side effects you might notice while on immune checkpoint inhibitors, Hann says. Most often, you can relieve them with over-the-counter (OTC) or light prescription meds. More serious side effects are less common and include severe allergic reactions, inflammation of organs (lungs, liver, intestines, or thyroid), and autoimmune reactions (where your immune system attacks healthy tissues).
Throughout your first-line treatment, your oncologist also tracks your health closely for other side effects that you might not notice.
Maintenance therapy for ES-SCLC
If scans show that the cancer is well controlled or stable after four cycles of chemo plus immunotherapy, your oncologist will likely talk with you about maintenance therapy. With ES-SCLC, this means you get more immunotherapy to help delay the cancer from worsening.
“At that point, we would really recommend involvement in clinical trials,” Hann says. “There are multiple that really look at this maintenance phase and think about ways that we can add other [medications].”
Another common option is to stay on the immunotherapy drug you took during your first-line treatment. If you took atezolizumab, that drug can be combined with a chemo drug called lurbinectedin (Zepzelca). This combo may help you live longer, but it also can raise the risk of you having more side effects. Also, lurbinectedin isn’t yet approved in many countries outside the U.S.
Second-Line Treatment Options for ES-SCLC
You might want to try a second-line treatment for various reasons. Maybe your first-line treatment didn’t work, or maybe its side effects were too harsh. Or perhaps the first-line treatment was a success, but your cancer showed signs of spreading more during maintenance therapy.
In the past, the only FDA-approved drug in the second-line setting for ES-SCLC was a type of chemotherapy drug called topotecan, Hann says. Studies showed that topotecan improved cancer symptoms but not how long people lived. “It remains part of therapy options, but it’s a tough regimen to give,” she says.
Today, an advanced immunotherapy drug called tarlatamab-dlle (Imdelltra) is the new standard of care among approved second-line treatments, experts say. “This drug has revolutionized the small-cell lung cancer space for patients with extensive-stage cancer,” Preeshagul says.
Gay agrees. “I think that’s been a real game changer for this disease. We’re seeing long-term remissions in patients that historically would have had weeks or, at most, a few months to live.”
Tarlatamab-dlle is so effective, he adds, that a study is underway to find out if the drug would work as a maintenance treatment. “If patients are really benefiting from this, we don’t want anyone to miss an opportunity to get it.”
If you want to try tarlatamab-dlle, be aware that you typically need to receive infusions of it in a hospital. And getting those infusions can be a challenge: Not all hospitals stock tarlatamab-dlle, and some hospitals aren’t equipped to manage a unique and serious side effect that it can cause.
Side effects of second-line treatment
Tarlatamab-dlle can cause cytokine release syndrome. This involves widespread inflammation that can lead to life-threatening conditions such as organ failure. If you get this side effect, it usually happens during or shortly after the first infusion on day 1 or the second infusion on day 8, Preeshagul says.
Cytokine release syndrome needs to be treated by an inpatient hospital team that’s trained to use a medicine called tocilizumab as an antidote, she says. In some cases, people come to Preeshagul for treatment help on those specific days when cytokine release syndrome is most likely to occur.
If your oncologist tells you they can’t offer you tarlatamab-dlle, ask them if they can connect you with another doctor or medical center that can, Gay says. Those who live farther from large medical centers may have to travel to find the treatment.
Clinical Trials for ES-SCLC
A common misconception about clinical trials is that they’re a “last resort.”
And that’s just not true, says Jacob Sands, MD, associate chief of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute in Boston.
“You may qualify for clinical trials when there aren’t other treatment options, but going on a trial is something that can happen as the first therapy at any point along the way.”
“Another common misconception is that people think that there’s a chance they’re just going to get placebo. And although there might be a placebo, it would be along with the best standard of care,” he says.
Ask your oncologist if they know of any clinical trials that are right for you. If they say no, ask if there are any trials outside of the institution where you are. It’s OK to get a second opinion.
One promising treatment in clinical trials today is antibody drug conjugates (ADCs), which mix targeted medicine and chemotherapy. ADCs use lab-made antibodies to target key cancer, then bombard those cells with small amounts of powerful chemo. The goal is to minimize damage to nearby healthy cells.
“They’re showing just unprecedented responses and durability of responses in small-cell lung cancer,” Gay says.
In terms of possible side effects, the most serious one tied to ADC use is inflammation of the lungs, or pneumonitis, Hann says. Doctors screen people carefully to determine if they are at risk for pneumonitis before starting the treatment.
When to Ask for a Second Opinion
You should feel empowered to ask another oncologist for a second opinion about your treatment plan at any time. “It’s OK to get a second opinion, and no one will give you a hard time about it. And if they do, [they’re] not a good fit,” Preeshagul says.
“I have a few patients right now who are on treatment that’s worked for more than a year, when they came to me reporting that their oncologist told them hospice was the only thing left,” Sands says.
When you’re searching for a second opinion, it’s important to find an oncologist who has lots of experience treating SCLC, he says.
Survival rates: ‘Don’t accept anyone’s number’
Maybe you’ve read or heard about the five-year survival rate for SCLC. It’s the estimated percentage of people with the disease who are still alive five years after they get diagnosed. But these estimates can’t predict what will happen with you. Keep in mind that “the search results have not quite caught up with the data yet,” Gay says. So, you may be seeing “somewhat-outdated information on there, whereas we know that there’s hope on the horizon.”
“Don’t accept anyone’s number,” Sands says. “There’s a broad range of possibilities that can happen with treatment as far as how long the disease can be controlled, as far as how long anyone can live.”
