SMALL CELL LUNG CANCER (SCLC) is an aggressive form of cancer that accounts for about 13% of all lung cancer cases. In 30% to 40% of those cases, the cancer is caught at the limited stage, while it is still confined to one lung and nearby tissues. The standard treatment has long been chemotherapy along with radiation (chemoradiation), but most people will have cancer return within two years of treatment.
On Dec. 4, 2024, the Food and Drug Administration (FDA) approved the immunotherapy Imfinzi (durvalumab) to treat limited-stage small cell lung cancer, after research showed the addition of Imfinzi could increase survival in people who had stable disease after chemoradiation. The approval allows more people with small cell lung cancer to benefit from immunotherapy, which had already been approved for extensive stage cases.
Treatment with chemoradiation was the standard for years because it produced the longest survival out of the available options at the time, according to Suresh Senan, a radiation oncologist at Amsterdam University Medical Centers in the Netherlands and an investigator on the study that led to Imfinzi’s approval. “However, five-year overall survival rates are only around 30%, with no advances made in the systemic treatment for more than three decades,” he says.
Small cell lung cancer typically progresses rapidly and often stops responding to chemotherapy, but the FDA approval marks progress.
The ADRIATIC Trial: Creating a New Standard of Care
The phase III ADRIATIC trial was published Sept. 13, 2024, in the New England Journal of Medicine. The study included 530 people whose cancer showed no progression after being treated with chemoradiation. In the study, half of these people received Imfinzi, while the other half received placebo.
People given Imfinzi lived a median 55.9 months compared with placebo’s 33.4 months. People in the Imfinzi group went a median of 16.6 months without cancer returning compared with a median of 9.2 months in the placebo.
“What was surprising was the magnitude of the observed benefits with Imfinzi versus placebo,” Senan says. Previous research in extensive stage disease had shown smaller improvements, about two months, in median overall survival with the addition of Imfinzi, he says.
“The results suggest the benefits from durvalumab might be greatest when it is started relatively quickly after chemoradiation,” says Kathryn Gold, a medical oncologist and clinical professor of medicine at UC San Diego Health who was not involved with the study. Outcomes for different subgroups in the study included a comparison of participants based on how long the lag was between standard treatment and starting either Imfinzi or a placebo. “The patients who started durvalumab therapy within two weeks of the end of chemoradiation tended to have more of a benefit than those who waited four weeks or more,” she says.
Gold adds that healthier patients may get the most benefit, as they may be better able to tolerate chemoradiation followed by immunotherapy. Chronic health issues can make it more challenging to manage immune-related side effects from drugs like Imfinzi, which work by activating the immune system and can cause inflammation in normal organs and tissues.
Next Steps in Limited-stage Small Cell Lung Cancer Treatment
While the ADRIATIC trial results have transformed limited-stage small cell lung cancer, not all immunotherapies have shown the same benefit. Data from the ACHILES trial, a randomized phase II trial presented at the 2025 American Society of Clinical Oncology Annual Meeting, held May 30 to June 3 in Chicago, showed that Tecentriq (atezolizumab) after chemoradiation did not improve the overall survival or time without cancer progression when compared with observation in people with limited-stage small cell lung cancer.
Gold says that the study supports Imfinzi as a standard of care for people with limited-stage small cell cancer. But researchers still have more to learn about immunotherapy in small cell lung cancer, including how other drugs and combinations may perform and if there are ways to better select who gets what treatment. “It would also be very helpful to have a biomarker to predict who might or might not benefit from immunotherapy,” Gold says.
Only 46% of patients who received Imfinzi in the study lived for two years without cancer progression, highlighting the need for additional treatment options for this aggressive cancer, Senan says. New treatments, including antibody-drug conjugates and bispecific T-cell engagers, have shown promise in extensive-stage cases and are moving into larger studies to see if they can further improve survival for people with limited-stage small cell lung cancer.
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