{"product_id":"osimertinib-after-chemoradiotherapy-for-stage-iii-egfr-mutated-lung-cancer-a-patient-guide-to-the-laura-trial","title":"Osimertinib After Chemoradiotherapy for Stage III EGFR-Mutated Lung Cancer: A Patient Guide to the LAURA Trial","description":"\u003cp\u003eIn a phase 3 clinical trial called LAURA, patients had unresectable stage III EGFR-mutated non-small-cell lung cancer. These patients had completed chemoradiotherapy without disease progression. They were randomly assigned to receive either osimertinib or placebo. Osimertinib produced a median progression-free survival of 39.1 months compared with 5.6 months for placebo, a hazard ratio of 0.16 (95% CI, 0.10 to 0.24; P\u0026lt;0.001). Interim overall survival at 36 months was 84% with osimertinib and 74% with placebo, a difference that was not yet statistically significant. Adverse events of grade 3 or higher occurred in 35% of patients receiving osimertinib and 12% of patients receiving placebo.\u003c\/p\u003e\n\n\u003ch1\u003eOsimertinib After Chemoradiotherapy for Stage III EGFR-Mutated Lung Cancer: A Patient Guide to the LAURA Trial\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#study-methods\"\u003eHow the Study Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#patient-characteristics\"\u003eWho Took Part in the Study\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#key-findings\"\u003eKey Findings: Progression-Free Survival\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#secondary-findings\"\u003eAdditional Findings: Response Rates, Spread of Disease, and Overall Survival\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSafety and Side Effects\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eWhat These Results Mean for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Study\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations and Questions to Ask Your Care Team\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn the LAURA trial, osimertinib after chemoradiotherapy improved median progression-free survival to 39.1 months versus 5.6 months with placebo in unresectable stage III EGFR-mutated NSCLC.\u003c\/li\u003e\n\u003cli\u003eThe hazard ratio for disease progression or death was 0.16, indicating an 84% reduction in risk with osimertinib compared with placebo.\u003c\/li\u003e\n\u003cli\u003eInterim overall survival at 36 months was 84% with osimertinib and 74% with placebo, but this difference was not statistically significant.\u003c\/li\u003e\n\u003cli\u003eGrade 3 or higher adverse events occurred in 35% of osimertinib patients versus 12% with placebo; the most common adverse event of any severity was radiation pneumonitis, while pneumonia was the most frequently reported adverse event of grade 3 or higher in both groups.\u003c\/li\u003e\n\u003cli\u003eThe trial excluded patients with interstitial lung disease, symptomatic pneumonitis, or unresolved grade 2+ adverse effects after chemoradiotherapy, and most participants were Asian.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eAbout 20 to 30% of patients with non-small-cell lung cancer (NSCLC, the most common type of lung cancer) have locally advanced stage III disease when they are first diagnosed. Among these patients, 60 to 90% are considered to have unresectable disease, meaning the tumor cannot be removed with surgery.\u003c\/p\u003e\n\n\u003cp\u003eThe current standard of care for unresectable stage III NSCLC is concurrent chemoradiotherapy (chemotherapy given at the same time as radiation therapy). This is followed by consolidation therapy with durvalumab in patients whose disease has not progressed after chemoradiotherapy. Durvalumab is an immune checkpoint inhibitor, a drug that helps the immune system attack cancer cells.\u003c\/p\u003e\n\n\u003cp\u003eEpidermal growth factor receptor (EGFR) mutations are found in up to one third of patients with unresectable stage III NSCLC who receive chemoradiotherapy. EGFR is a protein on the surface of cells that helps them grow and divide. When the EGFR gene is mutated, it can drive cancer growth. Currently, no targeted treatments are approved for patients with unresectable stage III EGFR-mutated NSCLC.\u003c\/p\u003e\n\n\u003cp\u003ePrevious studies have suggested that patients with unresectable stage III EGFR-mutated NSCLC have shorter or similar progression-free survival compared with patients without EGFR mutations. Progression-free survival is the time during which the cancer does not get worse. These patients also have a higher incidence of distant metastases after definitive chemoradiotherapy. Distant metastases are cancer that has spread to other parts of the body. This includes the central nervous system (CNS), which includes the brain and spinal cord.\u003c\/p\u003e\n\n\u003cp\u003eOf note, data suggest a lower risk of local failure in patients with EGFR-mutated disease. Local failure is failure of the primary tumor to regress or reappearance of the tumor at the primary site. Therefore, controlling systemic micrometastatic disease is critical to improving long-term outcomes in these patients. Systemic micrometastatic disease is tiny deposits of cancer cells that have spread throughout the body but are too small to detect.\u003c\/p\u003e\n\n\u003cp\u003eAlthough immune checkpoint inhibitors provide substantial overall survival benefit to patients with metastatic NSCLC without detectable EGFR mutations, the same benefit has not been shown in patients with EGFR-mutated NSCLC. Similarly, limited data show that the benefit of consolidation therapy with durvalumab specifically in patients with unresectable stage III EGFR-mutated NSCLC is uncertain.\u003c\/p\u003e\n\n\u003cp\u003eOsimertinib is a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI, a drug that blocks the activity of the EGFR protein). Osimertinib potently and selectively inhibits both EGFR-TKI sensitizing mutations and the EGFR p.Thr790Met resistance mutation. Osimertinib is the preferred first-line treatment for advanced EGFR-mutated NSCLC. Osimertinib is also approved for use in combination with platinum-based chemotherapy in this context. In addition, osimertinib is recommended as adjuvant treatment (treatment given after the main treatment) for resected stage IB–IIIA EGFR-mutated NSCLC.\u003c\/p\u003e\n\n\u003cp\u003eThe LAURA trial was designed to test whether osimertinib could help patients with unresectable stage III EGFR-mutated NSCLC who had completed chemoradiotherapy without disease progression.\u003c\/p\u003e\n\n\u003ch2 id=\"study-methods\"\u003eHow the Study Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003eThe LAURA trial was a phase 3, double-blind, placebo-controlled trial. In a double-blind trial, neither the patients nor the doctors know which treatment each patient is receiving. In a placebo-controlled trial, one group receives the active drug and the other group receives a placebo (a dummy treatment with no active ingredient).\u003c\/p\u003e\n\n\u003cp\u003eEligible patients were at least 18 years of age (20 years of age or older in Japan). All patients had locally advanced, unresectable, stage III NSCLC with an EGFR exon 19 deletion or exon 21 codon p.Leu858Arg point mutation (alone or with other EGFR mutations). All patients had a World Health Organization (WHO) performance-status score of 0 or 1. The WHO performance-status score is measured on a scale of 0 to 5, with higher numbers indicating greater disability.\u003c\/p\u003e\n\n\u003cp\u003eAt the time of recruitment, the disease stage was determined according to the eighth edition of the American Joint Committee on Cancer–Union for International Cancer Control staging guidelines.\u003c\/p\u003e\n\n\u003cp\u003eEligible patients had completed concurrent or sequential platinum-based chemoradiotherapy within 6 weeks before undergoing randomization. All patients were without investigator-assessed disease progression during or after definitive chemoradiotherapy.\u003c\/p\u003e\n\n\u003cp\u003ePatients with a history of interstitial lung disease (a group of lung conditions that cause scarring of the lungs) before chemoradiotherapy were not eligible. Patients with symptomatic pneumonitis (inflammation of the lungs) after chemoradiotherapy were not eligible. Patients with unresolved adverse effects of grade 2 or higher after chemoradiotherapy were also not eligible.\u003c\/p\u003e\n\n\u003cp\u003eAfter completing chemoradiotherapy, patients underwent randomization in a 2:1 ratio. This means that for every 2 patients assigned to osimertinib, 1 patient was assigned to placebo. Patients received either oral osimertinib at a dose of 80 mg once daily or placebo. Treatment continued until disease progression was shown by objective radiologic confirmation, as assessed by blinded independent central review, or until another discontinuation criterion was met.\u003c\/p\u003e\n\n\u003cp\u003eBlinded independent central review means that a group of experts who do not know which treatment each patient received reviewed the imaging scans to determine whether the cancer had progressed. This review was done according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, a standardized system for measuring how tumors change during treatment.\u003c\/p\u003e\n\n\u003cp\u003eAfter the occurrence of disease progression as assessed by blinded independent central review, patients in both treatment groups were offered open-label osimertinib. Open-label means that both the patients and the doctors knew which treatment was being given.\u003c\/p\u003e\n\n\u003cp\u003eThe primary end point was progression-free survival as assessed by blinded independent central review. Progression-free survival was defined as the time from randomization to objective disease progression or death from any cause in the absence of progression.\u003c\/p\u003e\n\n\u003cp\u003eKey secondary end points included overall survival, survival without progression of CNS disease (CNS progression–free survival), objective response rate, duration of response, health-related quality of life, and safety.\u003c\/p\u003e\n\n\u003cp\u003eTumor assessments with computed tomography (CT) or magnetic resonance imaging (MRI) of the chest and abdomen and MRI of the brain were required at baseline. Baseline assessments were done after the patient had undergone chemoradiotherapy and no later than 28 days before randomization. Assessments were then done every 8 weeks from the time of randomization for 48 weeks, and every 12 weeks thereafter until objective radiologic confirmation of disease progression.\u003c\/p\u003e\n\n\u003cp\u003eAdverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Adverse events of special interest were interstitial lung disease (comprising interstitial lung disease, pneumonitis, and pulmonary fibrosis) and radiation pneumonitis (comprising lung radiation fibrosis and radiation pneumonitis).\u003c\/p\u003e\n\n\u003cp\u003eProtocol-specified guidelines for management of adverse events allowed patients with interstitial lung disease or radiation pneumonitis of CTCAE grade 1 or 2 to continue or restart treatment.\u003c\/p\u003e\n\n\u003cp\u003eThe full analysis set included all the patients who had undergone randomization. This set provided the data that were used for summaries of the demographic and baseline characteristics and for efficacy analyses. The safety analysis set included all the patients who received at least one dose of osimertinib or placebo and provided the data that were used for safety analyses.\u003c\/p\u003e\n\n\u003cp\u003eProgression-free survival that was assessed by blinded independent central review was analyzed with the use of a log-rank test stratified according to the patients' disease stage (stage IIIA vs. stage IIIB or IIIC) before chemoradiotherapy. The Kaplan–Meier method was used to calculate median progression-free survival.\u003c\/p\u003e\n\n\u003cp\u003eTo control for the type I error rate at the 5% two-sided level, a sequential multiple testing procedure was used. If significance was shown in the analysis of progression-free survival, then overall survival would be tested, followed by testing for CNS progression–free survival.\u003c\/p\u003e\n\n\u003cp\u003eFor the primary analysis, the researchers calculated that 120 events of disease progression or death would provide the trial with 90% power. This power would detect a hazard ratio of 0.53 at a two-sided 5% significance level. The data-cutoff date was January 5, 2024.\u003c\/p\u003e\n\n\u003cp\u003eThe trial was conducted in accordance with the provisions of the Declaration of Helsinki. It also followed the Council for International Organizations of Medical Sciences International Ethical Guidelines. The trial adhered to the Good Clinical Practice guidelines of the International Council for Harmonisation. It complied with applicable laws and regulations. It also followed the policy of the trial sponsor, AstraZeneca, regarding bioethics and human biologic samples. The protocol was approved by the relevant institutional review boards or by independent ethics committees. All the patients provided written informed consent.\u003c\/p\u003e\n\n\u003cp\u003eThe trial was funded by the sponsor and designed by the sponsor in collaboration with the investigators. The sponsor was responsible for data collection and analysis and had a role in the interpretation of the data.\u003c\/p\u003e\n\n\u003ch2 id=\"patient-characteristics\"\u003eWho Took Part in the Study\u003c\/h2\u003e\n\n\u003cp\u003eFrom August 2018 through July 2022, a total of 216 patients underwent randomization. Of these, 143 patients were assigned to receive osimertinib, and 73 patients were assigned to receive placebo.\u003c\/p\u003e\n\n\u003cp\u003eThe characteristics of the patients at baseline were generally balanced between the two groups. However, the percentage of patients with a WHO performance-status score of 0 was higher in the osimertinib group (56%) than in the placebo group (42%).\u003c\/p\u003e\n\n\u003cp\u003eThe median age was 62 years in the osimertinib group (range, 36 to 84) and 64 years in the placebo group (range, 37 to 83).\u003c\/p\u003e\n\n\u003cp\u003eIn the osimertinib group, 53 patients (37%) were male and 90 patients (63%) were female. In the placebo group, 31 patients (42%) were male and 42 patients (58%) were female.\u003c\/p\u003e\n\n\u003cp\u003eRegarding smoking status, in the osimertinib group, 4 patients (3%) were current smokers, 37 patients (26%) were former smokers, and 102 patients (71%) had never smoked. In the placebo group, 1 patient (1%) was a current smoker, 23 patients (32%) were former smokers, and 49 patients (67%) had never smoked.\u003c\/p\u003e\n\n\u003cp\u003eRegarding race, in the osimertinib group, 116 patients (81%) were Asian and 27 patients (19%) were non-Asian. In the placebo group, 62 patients (85%) were Asian and 11 patients (15%) were non-Asian. The majority of the trial patients were enrolled from Asian countries. Consequently, some racial and ethnic subgroups were underrepresented, and no Black patients were enrolled.\u003c\/p\u003e\n\n\u003cp\u003eRegarding disease stage, in the osimertinib group, 52 patients (36%) had stage IIIA, 67 patients (47%) had stage IIIB, and 24 patients (17%) had stage IIIC. In the placebo group, 24 patients (33%) had stage IIIA, 38 patients (52%) had stage IIIB, and 11 patients (15%) had stage IIIC.\u003c\/p\u003e\n\n\u003cp\u003eRegarding histologic type (the type of cancer cells seen under a microscope), in the osimertinib group, 139 patients (97%) had adenocarcinoma, 3 patients (2%) had squamous-cell carcinoma, and 1 patient (1%) had another type. In the placebo group, 69 patients (95%) had adenocarcinoma, 2 patients (3%) had squamous-cell carcinoma, and 2 patients (3%) had another type.\u003c\/p\u003e\n\n\u003cp\u003eRegarding EGFR mutation type at screening, in the osimertinib group, 74 patients (52%) had an exon 19 deletion and 68 patients (48%) had an L858R mutation. In the placebo group, 43 patients (59%) had an exon 19 deletion and 30 patients (41%) had an L858R mutation.\u003c\/p\u003e\n\n\u003cp\u003eRegarding the type of chemoradiotherapy received, in the osimertinib group, 131 patients (92%) received concurrent chemoradiotherapy and 12 patients (8%) received sequential chemoradiotherapy. In the placebo group, 62 patients (85%) received concurrent chemoradiotherapy and 11 patients (15%) received sequential chemoradiotherapy.\u003c\/p\u003e\n\n\u003cp\u003eRegarding the best overall response to chemoradiotherapy, in the osimertinib group, 4 patients (3%) had a complete response, 67 patients (47%) had a partial response, 61 patients (43%) had stable disease, and 11 patients (8%) were not evaluable. In the placebo group, 3 patients (4%) had a complete response, 27 patients (37%) had a partial response, 37 patients (51%) had stable disease, and 6 patients (8%) were not evaluable.\u003c\/p\u003e\n\n\u003cp\u003eThe mean target-lesion size was 33±18 mm in the osimertinib group and 36±17 mm in the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eAll the patients who had undergone randomization received at least one dose of osimertinib or placebo. Discontinuation of the regimen occurred in 63 patients (44%) in the osimertinib group and in 66 patients (90%) in the placebo group. The most common reasons for discontinuation were disease progression (25% vs. 74%) and adverse events (13% vs. 7%).\u003c\/p\u003e\n\n\u003ch2 id=\"key-findings\"\u003eKey Findings: Progression-Free Survival\u003c\/h2\u003e\n\n\u003cp\u003eOsimertinib produced a significant progression-free survival benefit compared with placebo. This was the primary finding of the trial.\u003c\/p\u003e\n\n\u003cp\u003eA total of 120 events of disease progression (as assessed by blinded independent central review) or death occurred. This represents a total data maturity of 56%. There were 57 events in the osimertinib group (data maturity, 40%) and 63 events in the placebo group (data maturity, 86%).\u003c\/p\u003e\n\n\u003cp\u003eThe median follow-up for progression-free survival was 22.0 months (range, less than 0.1 to 60.6) with osimertinib and 5.6 months (range, less than 0.1 to 49.7) with placebo.\u003c\/p\u003e\n\n\u003cp\u003eThe median progression-free survival was 39.1 months (95% confidence interval [CI], 31.5 to not calculable) with osimertinib and 5.6 months (95% CI, 3.7 to 7.4) with placebo. A 95% confidence interval is a range of values that is likely to contain the true value for the whole population.\u003c\/p\u003e\n\n\u003cp\u003eThe overall hazard ratio for disease progression or death was 0.16 (95% CI, 0.10 to 0.24; P\u0026lt;0.001). A hazard ratio compares the risk of an event between two groups. A hazard ratio of 0.16 means that patients receiving osimertinib had an 84% reduction in the risk of disease progression or death compared with patients receiving placebo. The P value of less than 0.001 means there is less than a 0.1% chance that this result was due to random chance.\u003c\/p\u003e\n\n\u003cp\u003eThe percentages of patients who were alive and progression-free at 12 months were 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. At 24 months, the percentages were 65% (95% CI, 56 to 73) with osimertinib and 13% (95% CI, 6 to 22) with placebo.\u003c\/p\u003e\n\n\u003cp\u003eBeginning with the first postbaseline scan, Kaplan–Meier curves showed early separation between the treatment groups. This separation was sustained throughout follow-up. Investigator-assessed progression-free survival results were consistent with the findings of the blinded independent central review.\u003c\/p\u003e\n\n\u003cp\u003eThe progression-free survival benefit favoring osimertinib was observed in all prespecified subgroups with sufficient events for analysis. Hazard ratios ranged from 0.16 to 0.48.\u003c\/p\u003e\n\n\u003cp\u003eA progression-free survival benefit favoring osimertinib was also observed regardless of the patients' WHO performance-status score. This was assessed in a post hoc analysis (an analysis done after the study was completed). The hazard ratio for disease progression or death was 0.17 (95% CI, 0.10 to 0.28) for patients with a WHO performance-status score of 0 and 0.34 (95% CI, 0.20 to 0.56) for those with a WHO performance-status score of 1.\u003c\/p\u003e\n\n\u003ch2 id=\"secondary-findings\"\u003eAdditional Findings: Response Rates, Spread of Disease, and Overall Survival\u003c\/h2\u003e\n\n\u003cp\u003eThe objective response rate was higher with osimertinib than with placebo. The objective response rate is the percentage of patients whose cancer shrinks or disappears after treatment.\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eObjective response rate: 57% (95% CI, 49 to 66) with osimertinib vs. 33% (95% CI, 22 to 45) with placebo; odds ratio, 2.77 (95% CI, 1.54 to 5.08)\u003c\/li\u003e\n  \u003cli\u003eMedian duration of response: 36.9 months with osimertinib vs. 6.5 months with placebo\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eLower incidences of local progression and distant metastases were observed in the osimertinib group (21% and 16%, respectively) than in the placebo group (48% and 37%, respectively).\u003c\/p\u003e\n\n\u003cp\u003eThe incidence of new lesions was lower with osimertinib (22%) than with placebo (68%). This included new brain lesions (8% vs. 29%) and new lung lesions (6% vs. 29%).\u003c\/p\u003e\n\n\u003cp\u003eSubsequent anticancer treatment of any type was administered in 42 patients (29%) in the osimertinib group and 57 patients (78%) in the placebo group. Among the patients with disease progression, subsequent osimertinib treatment was administered in 15 of 53 patients (28%) in the osimertinib group and in 50 of 62 patients (81%) in the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eAs of the data-cutoff date, 43 of the patients had died (data maturity, 20%). The 36-month overall survival was 84% (95% CI, 75 to 89) with osimertinib and 74% (95% CI, 57 to 85) with placebo. The hazard ratio for overall survival was 0.81 (95% CI, 0.42 to 1.56; P = 0.53). This difference was not statistically significant at this interim analysis. An interim analysis is a planned analysis done before the study is complete.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety and Side Effects\u003c\/h2\u003e\n\n\u003cp\u003eAt the data-cutoff date, the median duration of total treatment exposure was 24.0 months (range, 0.4 to 62.9) with osimertinib and 8.3 months (range, 0.5 to 56.6) with placebo. The median duration of actual treatment exposure was similar — 23.7 months (range, 0.3 to 62.4) with osimertinib and 7.9 months (range, 0.5 to 56.2) with placebo.\u003c\/p\u003e\n\n\u003cp\u003eAdverse events were reported in 140 patients (98%) receiving osimertinib and 64 patients (88%) receiving placebo. The most common adverse events, irrespective of cause, were:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003eRadiation pneumonitis: 48% with osimertinib vs. 38% with placebo\u003c\/li\u003e\n  \u003cli\u003eDiarrhea: 36% with osimertinib vs. 14% with placebo\u003c\/li\u003e\n  \u003cli\u003eRash: 24% with osimertinib vs. 14% with placebo\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAdverse events of grade 3 or higher were reported in 50 patients (35%) with osimertinib and 9 patients (12%) with placebo. Grade 3 or higher means the side effect is serious or severe.\u003c\/p\u003e\n\n\u003cp\u003eSerious adverse events (irrespective of cause) were reported in 55 patients (38%) receiving osimertinib and in 11 patients (15%) receiving placebo.\u003c\/p\u003e\n\n\u003cp\u003eFatal adverse events occurred in 3 patients (2%) receiving osimertinib and in 2 patients (3%) receiving placebo. In the osimertinib group, the fatal events were pneumonitis, pneumonia, and a road traffic accident. In the placebo group, the fatal events were myocardial infarction (heart attack) and aortic aneurism rupture.\u003c\/p\u003e\n\n\u003cp\u003eThe adverse events that were grouped as interstitial lung disease were reported in 11 patients (8%) receiving osimertinib and 1 patient (1%) receiving placebo. These included the preferred terms interstitial lung disease (1% vs. 0%), pneumonitis (6% vs. 1%), and pulmonary fibrosis (2% vs. 0%).\u003c\/p\u003e\n\n\u003cp\u003eThe adverse events that were grouped as radiation pneumonitis were reported in 69 patients (48%) receiving osimertinib and in 28 patients (38%) receiving placebo. These included the preferred terms of radiation pneumonitis (48% vs. 38%) and lung radiation fibrosis (1% vs. 0).\u003c\/p\u003e\n\n\u003cp\u003eOf the patients in the osimertinib group who reported having radiation pneumonitis, 60 patients (87%) continued or restarted osimertinib treatment according to the trial guidelines for management of adverse events. These patients did not have subsequent recurrence of radiation pneumonitis.\u003c\/p\u003e\n\n\u003cp\u003eOverall, adverse events were responsible for dose interruptions in 80 patients (56%) receiving osimertinib and 18 patients (25%) receiving placebo. Dose reductions were needed in 12 patients (8%) receiving osimertinib and 1 patient (1%) receiving placebo. Discontinuation of osimertinib or placebo occurred in 18 patients (13%) and 4 patients (5%), respectively.\u003c\/p\u003e\n\n\u003cp\u003eNo new safety concerns emerged from the trial.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-implications\"\u003eWhat These Results Mean for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThe LAURA trial is a prospective phase 3 trial assessing the efficacy and safety of osimertinib in patients with unresectable stage III EGFR-mutated NSCLC amenable to curative-intent treatment. The trial met the prespecified criteria for the primary end point of progression-free survival as assessed by blinded independent central review.\u003c\/p\u003e\n\n\u003cp\u003eOsimertinib treatment after definitive chemoradiotherapy showed a significant benefit with regard to progression-free survival as compared with placebo. The hazard ratio for disease progression or death was 0.16 (95% CI, 0.10 to 0.24; P\u0026lt;0.001). This indicates an 84% reduction in the risk of disease progression or death with osimertinib as compared with placebo.\u003c\/p\u003e\n\n\u003cp\u003eThis means that for patients with unresectable stage III EGFR-mutated NSCLC who have completed chemoradiotherapy without disease progression, osimertinib offers a substantial delay in cancer progression compared with placebo. The median progression-free survival was 39.1 months with osimertinib compared with 5.6 months with placebo.\u003c\/p\u003e\n\n\u003cp\u003eThe progression-free survival benefit was consistent across all prespecified subgroups with sufficient events for analysis. This suggests that the benefit applies broadly to patients with this condition, regardless of age, sex, smoking status, disease stage, or EGFR mutation type.\u003c\/p\u003e\n\n\u003cp\u003eOsimertinib also reduced the incidence of new lesions, including new brain lesions. This is important because patients with EGFR-mutated NSCLC have a higher incidence of distant metastases, including in the central nervous system, after definitive chemoradiotherapy.\u003c\/p\u003e\n\n\u003cp\u003eThe overall survival data were not yet mature at the time of this analysis. The 36-month overall survival was 84% with osimertinib and 74% with placebo. The hazard ratio for overall survival was 0.81 (95% CI, 0.42 to 1.56; P = 0.53). This difference was not statistically significant at this interim analysis. Longer follow-up is needed to determine whether osimertinib improves overall survival compared with placebo.\u003c\/p\u003e\n\n\u003cp\u003eThe safety profile of osimertinib was consistent with its known safety profile. Adverse events of grade 3 or higher were more common with osimertinib (35%) than with placebo (12%). Radiation pneumonitis was the most common adverse event in both groups (48% with osimertinib vs. 38% with placebo). Most cases of radiation pneumonitis were grade 1 to 2. Most patients who developed radiation pneumonitis were able to continue or restart osimertinib without recurrence of radiation pneumonitis.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Study\u003c\/h2\u003e\n\n\u003cp\u003eThe majority of the trial patients were enrolled from Asian countries. Consequently, some racial and ethnic subgroups were underrepresented, and no Black patients were enrolled. This means that the results may not be fully generalizable to all patient populations.\u003c\/p\u003e\n\n\u003cp\u003eThe overall survival data were not mature at the time of this analysis. The data maturity for overall survival was 20%. This means that only 20% of the expected deaths had occurred. The overall survival difference between the two groups was not statistically significant at this interim analysis. Longer follow-up is needed to determine whether osimertinib improves overall survival.\u003c\/p\u003e\n\n\u003cp\u003eThe trial enrolled patients with a WHO performance-status score of 0 or 1. This means that all patients in the trial were relatively fit and able to carry out normal activities or light work. The results may not apply to patients with a worse performance status.\u003c\/p\u003e\n\n\u003cp\u003eThe trial excluded patients with a history of interstitial lung disease before chemoradiotherapy, symptomatic pneumonitis after chemoradiotherapy, or unresolved adverse effects of grade 2 or higher after chemoradiotherapy. The results may not apply to these patient groups.\u003c\/p\u003e\n\n\u003cp\u003eThe trial was funded by AstraZeneca, the manufacturer of osimertinib. The sponsor was responsible for data collection and analysis and had a role in the interpretation of the data.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations and Questions to Ask Your Care Team\u003c\/h2\u003e\n\n\u003cp\u003eIf you have unresectable stage III EGFR-mutated NSCLC and have completed chemoradiotherapy without disease progression, you may want to discuss the results of the LAURA trial with your care team. The following questions may be helpful:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003eAm I eligible for osimertinib treatment based on my specific EGFR mutation and disease stage?\u003c\/li\u003e\n  \u003cli\u003eWhat are the potential benefits of osimertinib for my situation?\u003c\/li\u003e\n  \u003cli\u003eWhat side effects should I watch for while taking osimertinib?\u003c\/li\u003e\n  \u003cli\u003eHow will my treatment response be monitored?\u003c\/li\u003e\n  \u003cli\u003eWhat should I do if I develop symptoms of radiation pneumonitis, such as new or worsening cough, shortness of breath, or fever?\u003c\/li\u003e\n  \u003cli\u003eAre there any clinical trials or other treatment options I should consider?\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eIt is important to remember that the LAURA trial showed a significant improvement in progression-free survival with osimertinib. However, the overall survival data were not yet mature. You should discuss the potential risks and benefits of osimertinib with your care team to make an informed decision about your treatment.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is the LAURA trial and who took part?\u003c\/h3\u003e\n\u003cp\u003eThe LAURA trial was a phase 3, double-blind, placebo-controlled study. It enrolled 216 patients with unresectable stage III EGFR-mutated non-small-cell lung cancer who had completed chemoradiotherapy without disease progression. Participants were at least 18 years old, had a WHO performance-status score of 0 or 1, and were randomly assigned in a 2:1 ratio to receive either osimertinib or placebo.\u003c\/p\u003e\n\u003ch3\u003eWhat were the main results of the LAURA trial?\u003c\/h3\u003e\n\u003cp\u003eIn the LAURA trial, osimertinib produced a median progression-free survival of 39.1 months compared with 5.6 months for placebo. The hazard ratio for disease progression or death was 0.16, meaning an 84% reduction in risk compared with placebo. This difference was statistically significant. The benefit was seen across prespecified subgroups with enough events for analysis.\u003c\/p\u003e\n\u003ch3\u003eWhat does a hazard ratio of 0.16 mean for patients?\u003c\/h3\u003e\n\u003cp\u003eA hazard ratio compares the risk of an event between two groups. In the LAURA trial, a hazard ratio of 0.16 for disease progression or death means that patients receiving osimertinib had an 84% lower risk of their cancer worsening or of death compared with those receiving placebo. This result was statistically significant, with a P value less than 0.001.\u003c\/p\u003e\n\u003ch3\u003eDid osimertinib improve overall survival in the LAURA trial?\u003c\/h3\u003e\n\u003cp\u003eAt the interim analysis, the 36-month overall survival was 84% with osimertinib and 74% with placebo. However, this difference was not statistically significant (hazard ratio 0.81; P=0.53). The overall survival data were not mature, with only 20% of expected deaths having occurred. Longer follow-up is needed to determine if osimertinib improves overall survival.\u003c\/p\u003e\n\u003ch3\u003eWhat side effects did patients experience with osimertinib?\u003c\/h3\u003e\n\u003cp\u003eIn the LAURA trial, adverse events of grade 3 or higher occurred in 35% of patients receiving osimertinib and 12% receiving placebo. The most common adverse events were radiation pneumonitis (48% vs 38%), diarrhea (36% vs 14%), and rash (24% vs 14%). Most radiation pneumonitis cases were grade 1 to 2, and many patients continued or restarted osimertinib without recurrence.\u003c\/p\u003e\n\u003ch3\u003eWho was not included in the LAURA trial?\u003c\/h3\u003e\n\u003cp\u003eThe LAURA trial excluded patients with a history of interstitial lung disease before chemoradiotherapy, symptomatic pneumonitis after chemoradiotherapy, or unresolved adverse effects of grade 2 or higher after chemoradiotherapy. It also only enrolled patients with a WHO performance-status score of 0 or 1, meaning relatively fit patients. Results may not apply to those excluded groups.\u003c\/p\u003e\n\u003ch3\u003eWhat should I ask my care team about osimertinib?\u003c\/h3\u003e\n\u003cp\u003eIf you have unresectable stage III EGFR-mutated NSCLC and completed chemoradiotherapy without progression, you may ask: Am I eligible for osimertinib based on my EGFR mutation and stage? What benefits and side effects should I expect? How will my response be monitored? What symptoms of radiation pneumonitis should I watch for? Are there other treatment options or clinical trials to consider?\u003c\/p\u003e\n\u003ch3\u003eI have unresectable stage III EGFR-mutated lung cancer and finished chemoradiotherapy without progression — when should I get a second opinion about taking osimertinib?\u003c\/h3\u003e\n\u003cp\u003eA second opinion can be useful once chemoradiotherapy is complete and imaging confirms no progression, since that is the point when osimertinib or placebo was started in the LAURA trial. Osimertinib produced a median progression-free survival of 39.1 months versus 5.6 months with placebo, with grade 3 or higher adverse events in 35% versus 12% of patients. An independent review of your pathology, EGFR mutation results and scans can help confirm eligibility and weigh benefits against side effects. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Osimertinib after Chemoradiotherapy in Stage III EGFR -Mutated NSCLC NEJM 2024\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Shun Lu, M.D., Terufumi Kato, M.D., Xiaorong Dong, M.D., Ph.D., Myung-Ju Ahn, M.D., Le-Van Quang, M.D., Nopadol Soparattanapaisarn, M.D., Takako Inoue, M.D., Chih-Liang Wang, M.D., Meijuan Huang, M.D., James Chih-Hsin Yang, M.D., Ph.D., Manuel Cobo, M.D., Mustafa Özgüroğlu, M.D., Ignacio Casarini, M.D., Dang-Van Khiem, M.D., Virote Sriuranpong, M.D., Ph.D., Eduardo Cronemberger, M.D., Toshiaki Takahashi, M.D., Ph.D., Yotsawaj Runglodvatana, M.D., Ming Chen, M.D., Ph.D., Xiangning Huang, Ph.D., Ellie Grainger, M.Sc., Dana Ghiorghiu, M.D., Ph.D., Toon van der Gronde, Pharm.D., Ph.D., and Suresh S. Ramalingam, M.D., for the LAURA Trial Investigators\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication:\u003c\/strong\u003e The New England Journal of Medicine, August 15, 2024, Volume 391, Number 7, pages 585-597\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e 10.1056\/NEJMoa2402614\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinicalTrials.gov number:\u003c\/strong\u003e NCT03521154\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e AstraZeneca\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47919017722012,"sku":null,"price":0.0,"currency_code":"KRW","in_stock":true}],"url":"https:\/\/diagnosticdetectives.kr\/products\/osimertinib-after-chemoradiotherapy-for-stage-iii-egfr-mutated-lung-cancer-a-patient-guide-to-the-laura-trial","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}