SINCE 2018, the standard of care for people with stage III non-small cell lung cancer (NSCLC) that cannot be treated with surgery has been to receive chemotherapy and radiation, followed by one year of the immunotherapy drug Imfinzi (durvalumab). However, several studies have indicated immunotherapy is less effective for patients with an epidermal growth factor receptor (EGFR) mutation, which occurs in up to one-third of NSCLC cases.

Now, a new standard of care exists for people with stage III NSCLC with an EGFR mutation. Results from the LAURA trial, published in the Aug. 15, 2024, issue of the New England Journal of Medicine, found the targeted therapy Tagrisso (osimertinib) delayed disease progression in this type of NSCLC better than a placebo during a three-year period.

“We were thrilled to see the extent of benefit with Tagrisso, which yielded an 84% reduction in the risk of death or disease progression,” says the study’s senior author, Suresh Ramalingam, a medical oncologist and executive director of Winship Cancer Institute at Emory University in Atlanta.

The study followed 216 people with stage III EGFR-mutated NSCLC who had completed chemoradiation: 143 received Tagrisso, which is an EGFR inhibitor, and 73 received a placebo. Those who received Tagrisso did not have disease progression for a median of 39.1 months, compared with a median of 5.6 months for people who received a placebo. At 12 months, 74% of patients in the Tagrisso group had no disease progression, compared with 22% of participants who took a placebo. In the placebo group, 81% of patients who had disease progression then chose to take Tagrisso. The study found 84% of people in the Tagrisso group were still alive at three years, compared with 74% of people in the placebo group.

About half of the Tagrisso group and 38% of the placebo group developed lung inflammation, the most common side effect in both groups. Other side effects seen more often in the Tagrisso group included diarrhea and rash. The study found 35% of Tagrisso patients and 12% of participants on a placebo experienced a serious adverse event.

Based on the study results, the Food and Drug Administration (FDA) approved Tagrisso for stage III EGFR-mutated lung cancer on Sept. 25, 2024. Prior to FDA approval, the American Society of Clinical Oncology and the National Comprehensive Cancer Network updated their guidelines to make Tagrisso the new standard of care for this indication.

The study results give patients and providers “a very clear and sensible path forward,” says Jorge Nieva, a medical oncologist at USC Norris Comprehensive Cancer Center in Los Angeles who was not involved in the study. “Patients currently receiving chemoradiation for stage III disease with an EGFR mutation should receive [Tagrisso] next. … The difference [in outcomes] is just too large to not undergo [Tagrisso] treatment.”

Nieva points out that using Tagrisso is well established in stage I, II and IV EGFR-mutated NSCLC. The FDA approved the drug in 2018 for people with EGFR-mutated NSCLC that has spread to distant parts of the body and, in 2020, expanded the approval to those with early-stage disease following surgery. “LAURA’s results confirm what we suspected, which is that stage III patients would also benefit from the use of an EGFR inhibitor,” he says.

Michael Menefee, a medical oncologist at Cleveland Clinic’s Taussig Cancer Institute who was not involved in the study, notes even stage III EGFR-mutated NSCLC that responds to chemoradiation is still likely to recur. These findings show Tagrisso “can delay the time it takes for the disease to manifest clinically, which can result in improved quality of life for patients,” he says.

How long people should receive treatment for remains unclear, Menefee says, noting study participants without progression still take Tagrisso. “Continuing the drug may be necessary to keep the cancer under control,” he says. “However, this will result in the overtreatment of some patients, increased financial burdens and potentially more toxicity.” Investigators continue to follow study participants to determine Tagrisso’s effect on overall survival. Additionally, researchers have started a trial to see if taking the targeted therapy before chemoradiation could improve outcomes in stage III EGFR-mutated NSCLC, and they hope future studies will identify biomarkers that can predict which patients would benefit the most, according to Ramalingam.