NSCLC is not a single disease—know the driver

EGFR mutations are an underlying, hidden driver of disease1

The EGFR gene makes a receptor protein called epidermal growth factor receptor, which promotes cell growth, division, and survival.

When mutated, EGFR drives cells to become abnormal and multiply uncontrollably.

PREVALENCE OF EGFR MUTATIONS IN ADENOCARCINOMA (ACROSS STAGES I-IV)2-5

EGFR mutations are prevalent across stages EGFR mutations are prevalent across stages *Prevalence of EGFR mutations in adenocarcinoma 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; and Jordan et al (2017) analyzed tumors from 860 patients with stage IV lung adenocarcinoma.3-6

Test every resectable and metastatic NSCLC patient for EGFR mutations

In resectable NSCLC

IN NSCLC, DISEASE MAY RECUR AS METASTASES THROUGHOUT THE BODY EVEN AFTER RESECTION7,8†

Micrometastases may remain after successful surgery Micrometastases may remain after successful surgery Chouaid et al (2018) conducted a retrospective observational study in 831 patients with complete resection of stage IB-IIIA NSCLC with no information on EGFRm status. Of the 831 patients, 200 experienced metastatic recurrence during the observed study follow-up period.8

Rule out EGFR mutations in resectable NSCLC

In resected NSCLC

Refer all resectable patients, test every surgical specimen. Test and confirm EGFR mutation status early on

Surgeon icon

DISCUSS
Adjuvant treatment and testing with patients

Doctor icon

INVOLVE A MEDICAL ONCOLOGIST
Refer patients to a medical oncologist as early as possible

Test for EFGR mutations at resection

TEST FOR EGFR MUTATIONS AT RESECTION
Ensure every surgical specimen is tested for EGFR mutations

A strong partnership between surgeons and medical oncologists helps establish optimal care for patients.

Learn more about why EGFRm status matters in resectable NSCLC

In metastatic NSCLC

Every metastatic NSCLC patient needs EGFRm testing

Smoking history, race, and gender are irrelevant—any patient may have an EGFR mutation9‡

Clinicopathologic features in EGFRm patients treated with EGFR TKIs Clinicopathologic features in EGFRm patients treated with EGFR TKIs

CLINICOPATHOLOGIC FEATURES IN EGFRm PATIENTS
TREATED WITH EGFR TKIs (N=1151)

EGFR TKI prescription data from Flatiron Health EHR-derived database. Included 1151 patients who started treatment between October 1, 2017, and April 30, 2020.9 §Calculations are based on those who specified race, and exclude the 157 patients in the study for whom race was not specified.9

In metastatic NSCLC

Be sure all eligible mNSCLC patients get the molecular testing they need

1 in 3 patients with lung adenocarcinoma has actionable mutations 1 in 3 patients with lung adenocarcinoma has actionable mutations

In metastatic NSCLC, EGFRm is one of a number of actionable mutations that can be treated with targeted therapy6,10,11

PD-L1 positive does not mean EGFR mutation negative

Up to 70% of EGFRm patients also express at least 1% PD-L112-16

Up to 70% of EGFRm patients also express at least 1% PD-L1 Up to 70% of EGFRm patients also express at least 1% PD-L1

Treatment-naïve metastatic EGFRm NSCLC patients were excluded in 11 pivotal first-line immunotherapy trials18-29
No single-agent or combination immunotherapies are FDA approved for treatment-naïve EGFRm mNSCLC patients30-32||
||Sensitizing EGFR mutations.17

  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.18-29

Don’t settle for unknown molecular status.
Test and confirm mutational status in every eligible metastatic patient

In metastatic NSCLC

Tissue testing barriers can be a challenge to identifying patients with EGFR mutations in the metastatic setting

Liquid biopsy plus tissue testing are critical to help find as many metastatic EGFRm NSCLC patients as possible

Liquid biopsy can help overcome the barriers of tissue testing Liquid biopsy can help overcome the barriers of tissue testing If liquid biopsy comes back negative, reflex to tissue biopsy.35 TAT is for next-generation sequencing.

Use liquid biopsy + tissue testing to help give more of your metastatic NSCLC patients the chance to benefit from targeted therapy

  • In a clinical study, liquid biopsy and tissue testing together increased detection of actionable mutations by 17% over mutations found in tissue34
NCCN Testing National Comprehensive Cancer Network® (NCCN®) recommends that repeat biopsy and/or plasma testing should be done if initial biopsy is insufficient in patients with metastatic NSCLC.17

TAGRISSO mechanism of action

TAGRISSO is designed to inhibit EGFR sensitizing and resistance mutations36-39

  • Inhibit EGFR sensitizing mutations—exon 19 del and L858R mutations
  • Inhibit mutated EGFR with the T790M resistance mutation
  • Have lower activity against wild-type EGFR
SELECTIVELY TARGETS BOTH EGFRm and EGFR T790M
TAGRISSO (osimertinib) Mechanism of Action targets both exon 19 deletions and L858R mutations and EGFR T790M
LOWER ACTIVITY AGAINST WILD-TYPE EGFR
TAGRISSO (osimertinib) Mechanism of Action has lower activity against wild-type EGFR

TAGRISSO crossed the blood-brain barrier (BBB) in preclinical models.36,40,41
TAGRISSO crossed the intact BBB in a study of healthy humans42#

#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.42

AEs, adverse events; ALK, anaplastic lymphoma kinase; AUC, area under the curve; BRAF, B-Raf proto-oncogene; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; EGFRm, epidermal growth factor receptor mutation positive; EHR, electronic health records; exon 19 del, exon 19 deletion; FDA, US Food and Drug Administration; L858R, exon 21 leucine 858 arginine substitution; MET, mesenchymal-epithelial transition; mNSCLC, metastatic non-small cell lung cancer; MRI, magnetic resonance imaging; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; PD-L1, programmed death-ligand 1; PET, positron emission tomography; PK, pharmacokinetics; QNS, quantity not sufficient; ROS1, ROS proto-oncogene 1; T790M, exon 20 threonine 790 methionine substitution; TAT, turnaround time; TKIs, tyrosine kinase inhibitors; WT, wild-type.

References: 1. Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12(1):3-20. 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. 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. 7. Uramoto H, Tanaka F. Recurrence after surgery in patients with NSCLC. Trans Lung Cancer Res. 2014;3(4):242-249. 8. Chouaid C, Danson S, Andreas S, et al; Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study. Lung Cancer. 2018;124:310-316. 9. Data on File. US-42770. EGFR TKI prescription data from Flatiron Health EHR-derived database (included patients who started treatment between October 2017 to April 2020, all data collected online). Ipsos data © Ipsos 2020, all rights reserved. AstraZeneca Pharmaceuticals LP. 10. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846. doi:10.1038/ncomms5846. 11. Bergethon K. Shaw AT, Ou SH, et al; ROS1 rearrangements define a unique molecular class of lung cancers. J Clin Oncol. 2012;30(8):863-870. 12. 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. 13. D'lncecco 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. 14. 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. 15. Yoneshima Y, ljichi K, Anai S, et al; PD-L1 expression in lung adenocarcinoma harboring EGFR mutations or ALK rearrangements. Lung Cancer. 2018;118:36-40. 16. 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. 17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.2.2021. ©National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed December 15, 2020. 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. 18. Reck M, Rodriguez-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. 19. 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. 20. 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. 21. Broderick JM. Frontline pembrolizumab combo improves survival in phase Ill NSCLC trial. https://www.onclive.com/web-excIusives/frontline-pembroIizumab-combo-improves-survival-in-phase-iii-nsclc-trial. Published January 16, 2018. Accessed November 20, 2020. 22. Carbone DP, Reck M, Paz-Ares L, et al; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017;376(25):2415-2426. 23. 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. 24. EU Clinical Trials Register. A phase Ill clinical study to evaluate the efficacy and safety of atezolizumab in combination with carboplatin + nab-paclitaxel compared with carboplatin + nab-paclitaxel in patients with stage IV non-squamous non-small cell lung cancer. EudraCT number 2014-003206-32. 25. 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. 26. Papadimitrakopoulou VA, Cobo M, Bordoni R, et al; IMpowerl32: 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. 27. 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/NCT03275706. Accessed July 1, 2020. 28. Spigel D, de Marinis F, Giaccone G, et al; lMpower110: interim overall survival (OS) analysis of a phase Ill 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. 29. 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. 30. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2020. 31. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc.; 2020. 32. Opdivo [package insert]. Princeton, NJ: Bristol-Meyers Squibb Company; 2020. 33. Leighl NB, Page RD, Raymond VM, et al; Clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer. Clin Cancer Res. 2019;25(15):4691-4700. 34. Aggarwal C, Thompson JC, Black TA, et al; Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer. JAMA Oncol. 2019;5(2):173-180. 35. Merker JD, Oxnard GR, Compton C, et al; Circulating tumor DNA analysis in patients with cancer. JAMA Oncol. 2019;5(2):173-180. 36. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 37. 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. 38. 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. 39. Finlay MR, Anderton M, Ashton S, et al; Discovery of a 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. 40. Ballard P, Yates JW, Yang Z, et al; Preclinical comparison of osimertinib with other EGFR-TKls in EGFR-mutant NSCLC brain metastases models, and early evidence of clinical brain metastases activity. Clin Cancer Res. 2016;22(20):5130-5140. 41. 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 TKls. Eur J Cancer. 2016;69:S28. 42. 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 Expand

  • 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


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