Knowing the molecular test results is a critical first step

EGFR, also known as epidermal growth factor receptor, is a genomic biomarker that identifies mNSCLC patients eligible for targeted therapy1

  • The National Comprehensive Cancer Network® (NCCN®) guidelines recommend testing patients with metastatic non-small cell lung cancer (NSCLC) for all actionable mutations, including EGFR, to ensure they receive optimal treatment2
Knowing biomarker test results is a critical first step Knowing biomarker test results is a critical first step

For your patients with resectable or metastatic NSCLC

Confirming your patient’s EGFR mutation status is a critical first step in resectable or metastatic NSCLC

Molecular testing for EGFR mutations in patients with resectable stage IB to IIIA NSCLC is now included in NCCN Guidelines® to inform adjuvant treatment decisions.1*

EGFR MUTATIONS ARE PREVALENT ACROSS STAGES IN ADENOCARCINOMA2-5‡

EGFR mutations are prevalent across Stages I-IV in Adenocarcinoma EGFR mutations are prevalent across Stages I-IV in Adenocarcinoma

EGFR mutations lead to unregulated proliferation and survival of tumor cells, making EGFR a key driver of disease regardless of stage2-4,6

TAGRISSO is a targeted therapy precisely designed to inhibit EGFR sensitizing mutations7

*The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays.1

Consider osimertinib for patients with completely resected stage IIB-IIIA and high-risk stage IB-IIA EGFRm NSCLC who received previous adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy.1

Prevalence of EGFR mutations in adenocarcinoma in stage I, II, III, and IV were based on data from 4 references; Sholl et al (2015) performed mutation analysis on 1007 specimens with confirmed diagnosis of stage I-IV lung adenocarcinoma; Jones et al (2019) analyzed genomic differences across pathologic stages I-III in an unspecified number of patients with lung adenocarcinoma; D’Angelo et al (2012) analyzed tumor specimens from a cohort of 1118 patients with stage I-III surgically resected lung adenocarcinomas; Jordan et al (2017) analyzed tumors from 860 patients with stage IV lung adenocarcinoma.3-5,8

For your patients with resectable NSCLC

It’s important to know the driver of disease

An EGFR mutation can be the hidden driver of disease. How can you help identify eligible EGFRm patients?9

Help support testing to confirm EGFRm status early on and ensure resectable NSCLC patients can have a chance to benefit from adjuvant TAGRISSO

EGFR (epidermal growth factor receptor) is a biomarker that, when mutated, can cause NSCLC to grow and spread. Knowing which of your patients have EGFR mutations can help you identify patients who are eligible for therapy that targets the mutation.10

Post-resection, make tissue testing and appropriate adjuvant therapy an integral part of your patient's treatment plan
  • Discuss icon
    DISCUSS

    adjuvant treatment and testing with patients

  • Medical oncologist icon
    REFER

    your patients to a medical oncologist as early as possible

  • Surgical specimen icon
    Help ENSURE

    every surgical specimen is tested for EGFR mutations

  • ADJUVANT TAGRISSO pill icon
     

    Give your eligible patients the chance to benefit fromADJUVANT TAGRISSO

Ensure institutional protocols are in place to help identify all EGFRm patients

Help your resectable NSCLC patients understand how important it is to get tested for EGFR mutations as early as possible, because testing can help determine what’s driving their disease and options may be available for adjuvant treatment

National Comprehensive Cancer Network recommendation Molecular testing for EGFR mutations in patients with resectable stage IB to IIIA NSCLC is now included in National Comprehensive Cancer Network® (NCCN®) Guidelines, to inform adjuvant treatment decisions.1*

Osimertinib (TAGRISSO) is the first and only EGFR TKI recommended by NCCN as adjuvant treatment for completely resected stage IB-IIIA EGFRm NSCLC.1* *The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays.1 Consider osimertinib for patients with completely resected stage IIB-IIIA and high-risk stage IB-IIA EGFRm NSCLC who received previous adjuvant chemotherapy or are ineligible to receive platinum-based chemotherapy.1
  • In studies, up to 70% of patients who tested positive for an EGFR mutation also expressed PD-L1 (also known as programmed death-ligand 1)11-15
  • In patients with metastatic EGFRm NSCLC, EGFR TKIs are the first-line FDA-approved and guideline-recommended option, independent of PD-L1 expression16
  • Treatment-naïve metastatic EGFRm NSCLC patients were excluded in 11 pivotal first-line immunotherapy trials17-28*

*KEYNOTE-024, KEYNOTE-042, KEYNOTE-021 Cohort G, KEYNOTE-189, CHECKMATE 026, CHECKMATE 227, CHECKMATE 9LA, IMpower110, IMpower130, IMpower132, and IMpower150. In the IMpower130 and IMpower150 trials, EGFRm patients were allowed only after progression on EGFR-TKI therapy or intolerance to EGFR-TKI treatment.

No immunotherapy is approved by the FDA for first-line use in metastatic EGFRm NSCLC29-31

Doctor with patient Doctor with patient

Confirm your patient has been tested icon Confirm your patient has been tested icon

Confirm that your patient has been tested for their full molecular profile

Check that all test results have been received icon Check that all test results have been received icon

Check that all test results have been received before starting treatment

Discuss all molecular test results with the physician icon Discuss all molecular test results with the physician icon

Discuss all molecular test results with the physician

It is important to confirm your mNSCLC patient’s EGFR mutation status before treatment initiation

TAGRISSO selectively targets EGFR sensitizing and resistance mutations7,32-34

TAGRISSO selectively targets EGFR sensitizing and resistance mutations TAGRISSO selectively targets EGFR sensitizing and resistance mutations

  • TAGRISSO crossed the blood-brain barrier (BBB) in preclinical models7,35,36
  • In a study, TAGRISSO crossed the BBB in healthy humans37

Study description: Eight (8) healthy male volunteers (age 52±8 years) were examined for ~90 minutes with PET imaging after single intravenous microdose (1.3 mcg; range 1.1-1.4 mcg) of 11C-labeled TAGRISSO. Concentrations of 11C-labeled TAGRISSO were also measured in arterial and venous blood and plasma. Brain MRI was acquired and used for co-registration of PET data and automatic delineation of regions of interest in the brain. PK parameters Cmax (brain), Tmax (brain), and AUC0–90 min brain/blood ratio were calculated. Safety and tolerability monitoring included recording of AEs, vital signs, and ECG.37

AEs, adverse events; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation positive; FDA, US Food and Drug Administration; L858R, exon 21 leucine 858 arginine substitution; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; PD-L1, programmed death-ligand 1; PET, positron emission tomography; PK, pharmacokinetics; T790M, exon 20 threonine 790 methionine substitution; TKI, tyrosine kinase inhibitor.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.4.2021. ©National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed March 3, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777 [supplementary appendix]. 3. Jones DR. Introducing tumor genomics to predict recurrence following complete resection of lung adenocarcinoma. Presented at: 2019 Annual Meeting of the American Association for Thoracic Surgery; May 4-7, 2019; Toronto, Canada. 4. 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. 5. Jordan EJ, Kim HR, Arcila ME, et al. Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies [published online ahead of print March 23, 2017]. Cancer Discov. doi:10.1158/2159-8290.CD-16-1337. 6. Black RC, Khurshid H. NSCLC: an update of driver mutations, their role in pathogenesis and clinical significance. R I Med J. 2015;98(10):25-28. 7. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 8. Sholl LM, Aisner DL, Varella-Garcia M, et al; LCMC Investigators. Multi-institutional oncogenic driver mutation analysis in lung adenocarcinoma: The Lung Cancer Mutation Consortium experience. J Thorac Oncol. 2015;10(5):768-777. 9. Chae YK, Oh MS. Detection of minimal residual disease using ctDNA in lung cancer: current evidence and future directions. J Thorac Oncol. 2019;14(1):16-24. 10. Shah RR, Shah DR. Safety and tolerability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in oncology. Drug Saf. 2019;42(2):181-198. 11. Akamine T, Takada K, Toyokawa G, et al. Association of preoperative serum CRP with PD-L1 expression in 508 patients with non-small cell lung cancer: a comprehensive analysis of systemic inflammatory markers. Surg Oncol. 2018;27(1):88-94. 12. D’Incecco A, Andreozzi M, Ludovini V, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015;112(1):95-102. 13. Liu SY, Dong ZY, Wu SP, et al. Clinical relevance of PD-L1 expression and CD8+ T cells infiltration in patients with EGFR-mutated and ALK-rearranged lung cancer. Lung Cancer. 2018;125:86-92. 14. Yoneshima Y, Ijichi K, Anai S, et al. PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK rearrangements. Lung Cancer. 2018;118:36-40. 15. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2020;15(1):138-143. 16. Brahmer JR, Govindan R, Anders RA, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC). J Immunother Cancer. 2018;6(1):75. 17. Reck M, Rodríguez-Abreu D, Robinson AG, et al; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1–positive non–small-cell lung cancer. N Engl J Med. 2016;375(19):1823-1833. 18. Clinicaltrials.gov. Study of MK-3475 (pembrolizumab) versus platinum-based chemotherapy for participants with PD-L1-positive advanced or metastatic non-small cell lung cancer (MK-3475-042/KEYNOTE-042). https://clinicaltrials.gov/ct2/show/NCT02220894. Accessed July 1, 2020. 19. Langer CJ, Gadgeel SM, Borghaei H, et al; KEYNOTE-021 Investigators. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508. 20. Broderick JM. Frontline pembrolizumab combo improves survival in phase III NSCLC trial. https://www.onclive.com/web-exclusives/frontline-pembrolizumab-combo-improves-survival-in-phase-iii-nsclc-trial. Published January 16, 2018. Accessed November 20, 2020. 21. Carbone DP, Reck M, Paz-Ares L, et al; CheckMate026 Investigators. First-line nivolumab in stage IV or recurrent non–small-cell lung cancer. N Engl J Med. 2017;376(25):2415-2426. 22. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104. 23. EU Clinical Trials Register. A phase III multicenter, randomized, open-label study evaluating the efficacy and safety of atezolizumab (MPDL3280A, anti-PD-L1 antibody) in combination with carboplatin+nab-paclitaxel for chemotherapy-naive patients with stage IV non-squamous non-small cell lung cancer. EudraCT number 2014-003206-32. 24. Kowanetz M, Socinski MA, Zou W, et al. IMpower150: efficacy of atezolizumab plus bevacizumab and chemotherapy across PD-L1 expression subgroups defined by the SP142 and SP263 IHC assays confirm all-comer benefit in 1L metastatic NSCLC. Presented at: AACR; April 14-18, 2018; Chicago, IL. 25. Papadimitrakopoulou VA, Cobo M, Bordoni R, et al. IMpower132: PFS and safety results with 1L atezolizumab + carboplatin/cisplatin + pemetrexed in stage IV non-squamous NSCLC [oral presentation]. Presented at: IASLC WCLC; September 23-26, 2018; Toronto, Canada. 26. Clinicaltrials.gov. A study of nivolumab and ipilimumab combined with chemotherapy compared to chemotherapy alone in first line NSCLC (CheckMate 9LA). https://clinicaltrials.gov/ct2/show/NCT03215706. Accessed July 1, 2020. 27. Spigel D, de Marinis F, Giaccone G, et al. IMpower110: interim overall survival (OS) analysis of a phase III study of atezolizumab (atezo) vs platinum-based chemotherapy (chemo) as first-line (1L) treatment (tx) in PD-L1–selected NSCLC. Presented at: European Society for Medical Oncology; September 27-October 1, 2019; Barcelona, Spain. Abstract LBA78. 28. Clinicaltrials.gov. A study of atezolizumab (MPDL3280A) compared with a platinum agent (cisplatin or carboplatin) + (pemetrexed or gemcitabine) in participants with stage IV non-squamous or squamous non-small cell lung cancer (NSCLC) [IMpower110]. https://clinicaltrials.gov/ct2/show/NCT02409342. Accessed July 1, 2020. 29. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2020. 30. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc.; 2020. 31. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2020. 32. Soria JC, Ohe Y, Vansteenkiste J, et al; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125. 33. Cross DA, Ashton SE, Ghiorghiu S, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014;4(9):1046-1061. 34. Finlay MR, Anderton M, Ashton S, et al. Discovery of potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014;57(20):8249-8267. 35. Ballard P, Yates JW, Yang Z, et al. Preclinical comparison of osimertinib with other EGFR-TKIs in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130-5140. 36. Colclough N, Ballard PG, Barton P, et al. Preclinical comparison of the blood brain barrier (BBB) permeability of osimertinib (AZD9291) with other irreversible next generation EGFR TKIs. Eur J Cancer. 2016;69:S28. 37. Varrone A, Varnäs K, Jucaite A, et al. A PET study in healthy subjects of brain exposure of 11C-labeled osimertinib–a drug intended for treatment of brain metastases in non-small cell lung cancer. J Cereb Blood Flow Metab. 2020;40(4):799-807.

IMPORTANT SAFETY INFORMATION

  • There are no contraindications for TAGRISSO
  • Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO-treated patients; 0.3% 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 occurred in TAGRISSO-treated patients. Of the 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% 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% of the 1479 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. 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% 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 Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM 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
  • 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%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough

INDICATIONS

  • 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

For additional information, please see the complete Prescribing Information, including Patient Information.

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