Despite a steady decrease in incidence over the past few decades, lung cancer is still the leading cause of cancer-related deaths in the United States.1 Approximately 85 percent of lung cancer diagnoses are categorized as non-small cell lung cancer (NSCLC), and treatment options have expanded in recent years.1,2
Surgery to remove a tumor is a standard of care for early-stage resectable NSCLC.3 Despite successful resection, a majority* of patients with resected stage IB-III NSCLC will experience disease recurrence or death within five years — with or without adjuvant treatment, including chemotherapy, radiation, or both.4
As one of the most common biomarkers in patients with NSCLC, EGFR mutations affect approximately one in every five patients7 — and patients with stage I-III EGFRm NSCLC may have a higher risk of metastatic recurrence.5
“Biomarker status is an important way to understand a patient’s disease, serving as an essential part of precision medicine and potentially opening up the door to try targeted therapy options,”6 said Erin A. Gillaspie, assistant professor of thoracic surgery in the department of thoracic surgery at Vanderbilt University Medical Center.
Improving Outcomes with Precision Oncology
TAGRISSO® is the first and only tyrosine kinase inhibitor (TKI) approved to treat adult patients with NSCLC harboring certain EGFR mutations (exon 19 deletions or exon 21 L858R mutations) as adjuvant treatment following tumor resection. The approval of TAGRISSO for adjuvant EGFRm NSCLC was based on the results from the global Phase III ADAURA trial.8
An initial analysis of TAGRISSO from the ADAURA trial examined disease-free survival (DFS) after surgical resection in patients with stage IB-IIIA EGFRm NSCLC. DFS results in the overall trial population, stage IB-IIIA, a key secondary endpoint, demonstrated a reduction in the risk of disease recurrence or death of 80 percent (based on HR of 0.20; 95 percent CI: 0.15, 0.27; p<0.0001). In patients with resected stage IB-IIIA EGFRm NSCLC, median DFS was not reached (95 percent CI: NE, NE) for TAGRISSO and was 27.5 months (95 percent CI: 22.0, 35.0) for placebo.**8
The trial was unblinded early, in 2020, at the recommendation of an independent data monitoring committee which determined that TAGRISSO demonstrated "overwhelming efficacy" in lung cancer patients.10
In the updated ADAURA DFS analysis, with 2 additional years of follow up, TAGRISSO reduced the risk of recurrence or death by 73 percent (HR=0.27; [95 percent CI: 0.21-0.34]) in the overall trial population (stages IB-IIIA). The median DFS was nearly five and a half years (65.8 months) (95 percent CI: 61.7, NC) in the overall population treated with TAGRISSO, and 28.1 months (95 percent CI: 22.1, 35.0) for placebo.*** This updated DFS analysis was a prespecified exploratory endpoint and was not powered to determine statistical significance.11
“The ADAURA trial brought adjuvant osimertinib as a standard-of-care treatment for eligible early-stage lung cancer patients who previously had no targeted treatment options after surgery,”8 said Wade T. Iams, assistant professor of medicine in the division of hematology/oncology in the department of medicine at Vanderbilt University Medical Center. “The results also highlight the importance of a multidisciplinary team approach to treatment in which surgeons and medical oncologists must work together to implement precision oncology and help improve outcomes.”12
ADAURA OS analysis presented at ASCO 2023 showed that TAGRISSO demonstrated statistically significant overall survival results in patients with stage IB-IIIA EGFRm NSCLC after complete tumor resection. TAGRISSO reduced the risk of death by 51 percent compared to placebo in both the primary analysis population (stages II-IIIA) (21 percent data maturity, OS HR of 0.49; 95 percent CI: 0.33-0.73; p<0.001), and in the overall trial population (stages IB-IIIA) (18 percent data maturity, OS HR of 0.49; 95 percent CI: 0.34-0.70; p<0.001). Median OS was not reached in either the TAGRISSO or placebo arm in the primary analysis population (stage II-IIIA) nor in the overall trial population (stage IB-IIIA).13
The ADAURA trial is a Phase III, double-blind, randomized, placebo-controlled, global trial in 682 patients with completely resected stage IB, II and IIIA NSCLC with or without adjuvant chemotherapy. Patients with NSCLC had centrally confirmed EGFR mutations (exon 19 deletion or exon 21 L858R mutation). Patients were randomized to either TAGRISSO (n=339; 80 mg orally, once daily) or placebo (n=343). The primary endpoint of the study was DFS by investigator assessment in stage II/IIIA patients. The secondary endpoints were DFS in the overall population (stage IB-IIIA); DFS rate at two, three, four and five years; overall survival (stage II/IIIA and overall population); safety; and health-related QoL. The planned treatment duration was 3 years or until disease recurrence/unacceptable toxicity.8,9
Serious adverse reactions were reported in 16 percent of patients treated with TAGRISSO. The most common serious adverse reaction (≥1 percent) was pneumonia (1.5 percent). The most common adverse reactions ≥ 10 percent observed in patients treated with TAGRISSO in the ADAURA trial were diarrhea (47 percent), rash (40 percent), nail toxicity (37 percent), stomatitis (32 percent), and dry skin (29 percent).8 Please see Important Safety Information below and a link to the complete Prescribing Information, including Patient Information, for TAGRISSO.
Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, noted that “it is remarkable that just [three] years ago, patients with early-stage EGFRm lung cancer had no targeted treatment options after surgery.”14
Beyond its indication as an adjuvant treatment for eligible patients with EGFRm NSCLC, TAGRISSO is also approved as a first-line therapy for patients with metastatic EGFRm (EGFR exon 19 deletions or exon 21 L858R mutations) NSCLC.8
IMPORTANT SAFETY INFORMATION
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 3.8 percent of the 1479 TAGRISSO-treated patients; 0.3 percent of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
- Heart rate-corrected QT (QTc) interval prolongation occurs in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8 percent were found to have a QTc >500 msec, and 3.1 percent of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
- Cardiomyopathy occurred in 3 percent of the 1479 TAGRISSO-treated patients; 0.1 percent of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10 percent from baseline and to <50 percent LVEF occurred in 3.2 percent of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5 percent (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10 percent from baseline and a drop to <50 percent. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
- Keratitis was reported in 0.7 percent of 1479 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
- Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed.
- Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
- Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07 percent of 1479) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
- Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
- Most common (≥20 percent) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough
- TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
- TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
- TAGRISSO is indicated for the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy
Please see complete Prescribing Information, including Patient Information for TAGRISSO.
CI, confidence interval; DFS, disease-free survival; EGFRm, epidermal growth factor receptor mutation-positive; HR, hazard ratio; NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival.
- American Cancer Society. Key statistics for lung cancer. Available at: https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed August 18, 2023.
- Howlader N, Forjaz G, Mooradian MJ, et al. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020;383(7):640-649.
- Raman V, Yang CJ, Deng JZ, D’Amico TA. Surgical treatment for early stage non-small cell lung cancer. J Thorac Dis. 2018;10(Suppl 7):S898-S904.
- Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J Clin Oncol. 2008;26:3552-3559.
- Galvez C, Jacob S, Finkelman BS, et al. The role of EGFR mutations in predicting recurrence in early and locally advanced lung adenocarcinoma following definitive therapy. Oncotarget. 2020;11(21):1953-1960.
- National Cancer Institute. Biomarker Testing for Cancer Treatment. Accessed August 18, 2023. Available at: https://www.cancer.gov/about-cancer/treatment/types/biomarker-testing-cancer-treatment#is-biomarker-testing-part-of-precision-medicine.
- D'Angelo SP, Janjigian YY, Ahye N, et al. Distinct clinical course of EGFR-mutant resected lung cancers: results of testing of 1118 surgical specimens and effects of adjuvant gefitinib and erlotinib. J Thorac Oncol. 2012;7(12):1815-1822.
- TAGRISSO® (osimertinib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023.
- Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020; 383(18):1711-1723.
- AstraZeneca. TAGRISSO Phase III ADAURA trial will be unblinded early after overwhelming efficacy in the adjuvant treatment of patients with EGFR-mutated lung cancer [press release]. Published April 10, 2020. Accessed August 18, 2023. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2020/tagrisso-phase-iii-adaura-trial-will-be-unblinded-early-after-overwhelming-efficacy-in-the-adjuvant-treatment-of-patients-with-egfr-mutated-lung-cancer-04102020.html#
- 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. 2023;41(10):1830-1840.
- Bilfinger TV, Albano D, Perwaiz M, et al. Survival outcomes among lung cancer patients treated using a multidisciplinary team approach. Clin Lung Cancer. 2018;19(4):346-351.
- Tsuboi M, Herbst RS, John T, et al. Overall survival with osimertinib in resected EGFR-mutated NSCLC. N Engl J Med. 2023;389:137-147.
- AstraZeneca. Tagrisso demonstrated 5.5-year median disease-free survival in the adjuvant treatment of patients with EGFR-mutated lung cancer [press release]. Published September 11, 2022. Accessed August 18. 2023. https://www.astrazeneca.com/media-centre/press-releases/2022/tagrisso-demonstrated-5-year-median-disease-free-survival-in-the-adjuvant-treatment-of-patients-with-egfr-mutated-lung-cancer.html.
* "majority of patients" means: "In a pooled analysis of 5 randomized trials with 4584 patients with completely resected NSCLC (trials compared postoperative cisplatin-based chemotherapy versus no chemotherapy or cisplatin-based chemotherapy plus postoperative radiotherapy, administered sequentially vs postoperative radiotherapy alone), 45 percent of patients with stage IB, 62 percent of patients with stage II, and 76 percent of patients with stage III experienced recurrence or death within 5 years."4
** Secondary endpoint in the ADUARA initial analysis. Primary endpoint in the initial analysis at 2 years was DFS in patients with resected stage II-IIIA EGFRm NSCLC. Median DFS was not reached for TAGRISSO (95 percent CI: 38.8, NE) and was 19.6 months (95 percent CI: 16.6, 24.5) for placebo (HR=0.17 [95 percent CI: 0.12, 0.23]; P<0.0001).8