Patients with locally advanced, unresectable (not able to be surgically removed), stage 3 non–small cell lung cancer (NSCLC) with an EGFR mutation experienced improvements in progression-free survival (PFS; how long a patient lives without their disease spreading or worsening) following treatment with Tagrisso (osimertinib) after definitive chemoradiotherapy when compared with patients who received placebo, according to findings from the phase 3 LAURA trial.
Findings presented during a press briefing at the 2024 ASCO Annual Meeting demonstrated that treatment with Tagrisso reduced the risk of progression or death by 84% compared with placebo. Patients treated with Tagrisso (143 patients) experienced a median PFS of 39.1 months versus 5.6 months for patients who received placebo (73 patients).
The 12- and 24-month PFS rates in the Tagrisso arm were 74% and 65%, respectively. Those respective rates were 22% and 13% in the placebo arm.
“Based on these results, [Tagrisso] will become the new standard of care for patients with [EGFR-mutated], locally advanced NSCLC following definitive chemoradiation. EGFR mutation testing should be conducted for patients with stage 3 disease in order for patients to achieve optimal outcomes,” lead study author Dr. Suresh S. Ramalingam, executive director of Winship Cancer Institute of Emory University and associate vice president for cancer of Woodruff Health Sciences Center in Atlanta said in the press briefing.
Notably, no targeted therapies are currently approved for patients with EGFR-mutated, unresectable, stage 3 NSCLC.
LAURA was a trial that enrolled patients at least 18 years of age (or at least 20 years of age in Japan) with locally advanced (cancer that has grown beyond where it started but not spread to other parts of the body), unresectable, stage 3 NSCLC harboring an EGFR exon 19 deletion or L858R mutation who did not experience disease progression following definitive chemoradiotherapy. Patients needed to have a WHO performance status of 0 or 1 (patients may be restricted from strenuous activity but can perform daily tasks) and the maximum interval between the last dose of chemoradiotherapy and randomization was six weeks.
Patients were randomly assigned to receive oral Tagrisso or placebo once per day. Treatment continued until disease progression, unacceptable side effects or other discontinuation criteria were met.
Notably, patients in both arms were permitted to receive Tagrisso following disease progression. Tumor assessments were conducted via chest CT/MRI and brain MRI at baseline, then once every eight weeks until week 48, then once every 12 weeks thereafter until progression.
Stratification factors included method of chemoradiotherapy (chemotherapy and radiation given together vs one after the other), disease stage (3A versus 3B/C) and location (China versus not China).
PFS served as the trial’s main goal. Secondary end points included overall survival (OS; the time a patient lives, regardless of disease status), central nervous system PFS and safety.
OS data were not ready at data cutoff; however, Ramalingam noted that a trend favoring Tagrisso was observed, “[despite] a high proportion of patients crossing over from the control arm [81%].”
Additional data showed 22 patients in the Tagrisso arm experienced new tumors compared with 68 patients in the placebo arm. Sites of new lesions included the brain (Tagrisso, eight patients; placebo, 29 patients), lung (six; 29), liver (three; seven), lymph nodes (one; seven), bone (one; one), adrenal (one; zero), peritoneum/omentum (one; zero), pelvis (one; zero), spleen (zero; one) and other (one; zero).
Regarding safety, Ramalingam said findings for Tagrisso following chemoradiotherapy were consistent with the known safety profile of the EGFR inhibitor and manageable, noting that most side effects were not serious, were grade 1/2 (mild/moderate) and did not lead to treatment discontinuation.
The most common any-grade side effects reported in at least 10% of patients included radiation pneumonitis (inflammation of the lungs due to radiation therapy, Tagrisso, 48%; placebo, 38%), diarrhea (36%; 14%), rash (24%; 14%), COVID-19 (20%; 8%), skin infection around the nails, 17%; 1%), cough (16%; 10%), decreased appetite (15%; 5%), dry skin (13%; 5%), itching (13%; 7%), stomatitis (inflamed or irritated mucus membranes in the mouth, 12%; 3%), decreased white blood cell count (12%; 3%), pneumonia (11%; 8%), anemia (low red blood cell count, 10%; 4%) and musculoskeletal chest pain (3%; 12%).
Grade 3 (severe) or higher side effects in the Tagrisso arm included pneumonia (3%), radiation pneumonitis (2%), diarrhea (2%), COVID-19 (1%), decreased appetite (1%), dry skin (1%), decreased white blood cell count (1%) and anemia (1%).
“The LAURA trial is the first to define the role of EGFR-directed therapy in unresectable stage 3 disease. While the study did not compare [Tagrisso] to the current standard-of-care immunotherapy, these data have major implications for both patients and oncologists and will change the standard of care for patients with EGFR mutations,” Dr. David R. Spigel, chief scientific officer of Sarah Cannon Research Institute in Nashville, Tennessee, stated in a news release.
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