ASCO has issued a rapid update to its guideline on the management of stage III non–small cell lung cancer (NSCLC), based on the results of the phase III LAURA trial, which was presented at the 2024 ASCO Annual Meeting and published simultaneously in The New England Journal of Medicine.1,2 The guideline includes a recommendation for the use of the EGFR tyrosine kinase inhibitor osimertinib following definitive chemoradiotherapy in patients with unresectable stage III NSCLC with an EGFR exon 19 deletion or exon
21 L858R mutation.
Navneet Singh, MD, DM, FRCP, FASCO
Megan E. Daly, MD
“Osimertinib demonstrated an impressive improvement in progression-free survival,” said Navneet Singh, MD, DM, FRCP, FASCO, of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, and Co-Chair of the ASCO Expert Panel. “This represents a new therapeutic option for patients with EGFR-mutated unresectable stage III NSCLC following completion of chemoradiotherapy.”
Megan E. Daly, MD, of the UC Davis Comprehensive Cancer Center, acted as Co-Chair with Dr. Singh.
Positive Results of the LAURA Trial
The LAURA trial, which was the first study to assess a targeted agent in patients with unresectable stage III NSCLC, included 216 patients randomly assigned 2:1 to receive either osimertinib (143 patients) or placebo (73 patients). The median progression-free survival with osimertinib was 39.1 months compared with 5.6 months with placebo (hazard ratio [HR] = 0.16, 95% confidence interval [CI] = 0.10–0.24; P < .001).2
The progression-free survival benefit seen with osimertinib was consistent across a variety of predefined and exploratory subgroups. These subgroups included stage IIIA vs IIIB/IIIC disease, concurrent vs sequential chemoradiotherapy, the type of EGFR mutation, smoking history, and others. Overall survival was only 20% mature at the time of publication; per the study’s protocol, patients who received placebo were permitted to cross over and receive osimertinib after disease progression, and 81% of patients did so.
“Demonstration of overall survival benefit is, to put it more aptly, the final benchmark for efficacy of any new therapeutic strategy. Given the impressive progression-free survival benefit, mature overall survival data [are] keenly awaited, and clinicians as well as patients would certainly hope the progression-free survival benefit observed with consolidation osimertinib translated into an overall survival benefit of similar magnitude,” Dr. Singh said. “Pending overall survival data, the impressive progression-free survival benefit certainly mandates that osimertinib as consolidation therapy should be discussed with all patients with EGFR-mutated advanced/unresectable stage III NSCLC at completion of chemoradiotherapy.”
A New Standard of Care
The guideline update considers the evidence quality for the inclusion of osimertinib as moderate, and the recommendation is considered “strong.”1 Other parts of the guideline on the management of stage III NSCLC remain unchanged.
Between 20% and 30% of the 2 million patients diagnosed with NSCLC annually have stage III disease, and as many as 90% of these patients have unresectable disease.3 Before the LAURA trial, consolidation therapy with durvalumab was considered the standard of care for these patients, in spite of uncertain benefits. Now, that standard has changed.
“Importantly, these patients should not be offered durvalumab consolidation,” Dr. Singh said.
Accounting for Adverse Events
In LAURA, patients who received osimertinib experienced more grade 3 or higher adverse events than those who received placebo (35% vs 12%). Radiation pneumonitis (48% vs 38%) and adverse events that led to discontinuation of therapy (13% vs 5%) were also somewhat more common with osimertinib. Adverse events led to dose interruptions or dose reductions in 56% and 8%, respectively, of patients who received osimertinib, compared with 25% and 1% of those receiving placebo.2
Dr. Singh said that clinicians must be aware of the higher rate of some adverse events with osimertinib and “should discuss the possible pros and cons with every patient in order to reach an informed decision for this new therapeutic strategy.”
Emphasizing Biomarker Testing
Suresh S. Ramalingam, MD, FACP, FASCO
The Expert Panel stressed that the results of the LAURA trial—in conjunction with results of other studies, including ADAURA and PACIFIC—demonstrate the importance of molecular testing for oncogenic driver alterations.2,4,5 Patients with EGFR mutations benefit from an EGFR-targeted drug, rather than immune checkpoint inhibition. LAURA “reemphasizes the need for predictive biomarker testing—especially EGFR mutations—in all disease stages of NSCLC,” Dr. Singh said.
Suresh S. Ramalingam, MD, FACP, FASCO, of the Winship Cancer Institute at Emory University, presented the results of the LAURA trial at the 2024 ASCO Annual Meeting. He said then that osimertinib will “provide the new standard of care for EGFR-mutant disease in this setting.”
REFERENCES
1. Daly ME, Singh N, Ismaila N: Management of stage III non–small cell lung cancer: ASCO rapid guideline update. J Clin Oncol 42:3058-3060, 2024.
2. Lu S, Kato T, Dong X, et al: Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med 391:585-597, 2024.
3. Zhang Y, Vaccarella S, Morgan E, et al: Global variations in lung cancer incidence by histological subtype in 2020: A population-based study. Lancet Oncol 24:1206-1218, 2023.
4. Herbst RS, Wu YL, John T, et al: Adjuvant osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: Updated results from the phase III randomized ADAURA trial. J Clin Oncol 41:1830-1840, 2023.
5. Spigel DR, Faivre-Finn C, Gray JE, et al. Five-year survival outcomes from the PACIFIC trial: Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. J Clin Oncol 40:1301-1311, 2022.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, July 23, 2024. All rights reserved.
