THE BODY’S IMMUNE SYSTEM uses T cells to destroy pathogens, like bacteria and viruses, as well as cancer cells. Normal cells, such as those in the heart, liver and lungs, express proteins like PD-L1 that “switch off” the T cells, preventing them from attacking healthy tissue. However, some cancer cells use the same proteins to hide from T cells, allowing them to evade the immune system.

Immune checkpoint inhibitors (ICIs) are a class of anticancer drugs that prevent cancer cells from switching off T cells, allowing them to attack the disease. Since the Food and Drug Administration approved the first ICIs for metastatic non-small cell lung cancer (NSCLC) in 2015, these drugs have become a pillar of metastatic lung cancer treatment. Doctors increasingly use ICIs for early-stage lung cancers too. “They’ve really revolutionized the care and the outcomes for patients with lung cancer,” says Mark Awad, the chief of thoracic oncology at Memorial Sloan Kettering Cancer Center in New York City.

But sometimes “the immune cells go a little haywire and attack normal parts of the body” in people receiving ICIs and cause side effects, Awad adds. Some side effects, such as inflammation of the colon, lungs or liver, can be so severe that up to 25% of people pause or stop treatment. “For patients, and also for clinicians, there can be some anxiety if treatment has to be held or stopped due to side effects. People worry, understandably, what’s going to happen to the cancer,” Awad says.

To assess how stopping treatment impacts disease progression, Awad and colleagues examined medical records from 271 people with advanced NSCLC who discontinued ICI treatment due to side effects between 2011 and 2022. In the study, published April 18, 2025, in Clinical Cancer Research, researchers looked at cancer progression and survival after ICI discontinuation. Participants lived a median of 12.7 months -without cancer progression and survived a median of 43.7 months—more than 3.5 years. Researchers found 46% of patients remained alive five years after starting the ICI. For comparison, about 12% of people with metastatic NSCLC survive five years from their diagnosis.

Awad spoke with Cancer Today about the findings and how ICIs can lead to durable disease control.

CT: What were the most interesting findings of your study?

AWAD: Some patients had very long survival after stopping immunotherapy. People who stopped immunotherapy within three months of starting the treatment lived a median of 22 months post discontinuation. Those who stopped between three and six months lived a median of 43 months, and those who stopped after six months lived a median of 87 months. That’s years of survival after immunotherapy was discontinued, which is not typical for patients with metastatic lung cancer. So the longer you were on treatment before it had to be stopped for toxicity, the better you did afterwards.

CT: What other factors were associated with better outcomes following treatment discontinuation?

AWAD: A higher PD-L1 score, which indicates the percentage of tumor cells that express the checkpoint protein PD-L1, was also associated with longer post-discontinuation benefit.  And then having a partial response or a complete response, where the cancer shrank down substantially, compared to patients who had stable disease, was associated with improved long-term outcomes.

CT: Why did patients continue to benefit after they stopped taking the immune checkpoint inhibitor?

AWAD: When you get vaccines as a kid, sometimes you only need it once in your life. Your immune cells can offer protection against certain infections for the rest of your life, so we know that the immune cells can continue working for long periods of time. We suspect the same occurs in cancer. If you can generate a good or a potent antitumor response with your immune cells, then we hope that the immune cells can keep working, keeping the cancer in check even long after the medication has gone out of the system.

CT: What do the results mean for people who experience side effects from immunotherapy?

AWAD: Patients who stop immunotherapy due to side effects don’t necessarily have to immediately switch to a different type of systemic therapy. In many cases, they can have durable control of their cancer even while treatment has been paused. We want to offer some reassurance that stopping treatment doesn’t necessarily mean that the cancer is going to start regrowing immediately. Some patients have chronic low-grade side effects, like fatigue or joint or muscle aches and pains, that don’t necessarily mandate discontinuation but can interfere with day-to-day quality of life. Because of studies like this, we can have more discussions with patients about potentially stopping ICIs.

This interview has been edited and condensed for clarity.