Knowing the biomarker 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

Metastatic NSCLC patients who express PD-L1 can also have an EGFR mutation3-7

  • 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)3-7
  • In patients with EGFRm mNSCLC, EGFR TKIs are the first-line recommended option, independent of PD-L1 expression8
  • Treatment-naïve metastatic EGFRm NSCLC patients were excluded in 8 pivotal first-line immunotherapy trials9-16*

*KEYNOTE-189, KEYNOTE-021 Cohort G, KEYNOTE-042, KEYNOTE-024, CHECKMATE 026, CHECKMATE 227, IMpower130, and IMpower150. In the IMpower130 and IMpower150 trials, EGFRm-positive 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 NSCLC17-19

Plasma testing may help find mutations that tissue biopsy alone would miss Plasma testing may help find mutations that tissue biopsy alone would miss

Plasma testing may help find mutations that tissue biopsy alone would miss20,21

  • Ensure that your patients have had both plasma and tissue testing to confirm their mutational status, especially when:
  • There was not enough tissue from the biopsy or biopsy was not feasible
  • Faster turnaround time is needed

Help ensure your patients get the best treatment for their disease

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 mutations22-24

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 models25-28
  • In a study, TAGRISSO crossed the BBB in healthy humans28

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 AUC0–90min brain/blood ratio were calculated. Safety and tolerability monitoring included recording of AEs, vital signs and ECG.28

AUC, area under the curve; AEs, adverse events; ECG, electrocardiogram; EGFRm, epidermal growth factor receptor mutant; FDA, US Food and Drug Administration; mNSCLC, metastatic non-small cell lung cancer; MRI, magnetic resonance imaging; PET, positron emission tomography; PK, pharmacokinetics; TKI, tyrosine kinase inhibitor.

References: 1. Shah RR, Shah DR. Safety and tolerability of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in oncology. Drug Saf. 2019;42:181-198. 2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.2.2020. ©National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed December 23, 2019. 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. 3. 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. 4. 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. 5. 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. 6. 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. 7. Brown H, Vansteenkiste JF, Nakagawa K, et al. PD-L1 expression in untreated EGFRm advanced NSCLC and response to osimertinib and SoC EGFR-TKIs in the FLAURA trial. Presented at: IASLC WCLC; September 23-26, 2018; Toronto, Canada. 8. 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. 9. 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. 10. Clinicaltrials.gov. Study of pembrolizumab (MK-3475) versus platinum-based chemotherapy for participants with programmed cell death-ligand (PD-L1)-positive advanced or metastatic non-small cell lung cancer (MK-3475-042/KEYNOTE-042). https://clinicaltrials.gov/ct2/show/NCT02220894. Accessed January 9, 2019. 11. 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. 12. 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 August 15, 2019. 13. 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. 14. 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. 15. EU Clinical Trials Register. A phase III 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. https://www.clinicaltrialsregister.eu/. Accessed August 15, 2019. 16. 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. 17. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2019. 18. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc; 2019. 19. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2019. 20. 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. 21. Leighl N, Page R, Raymond V, 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. 22. 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. 23. 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. 24. 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. 25. TAGRISSO [package insert]. Wilmington DE: AstraZeneca Pharmaceuticals LP; 2019. 26. 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. 27. Colclough N, Ballard P, 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. 28. 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. 2019. doi:10.1177/0271678X19843776.

IMPORTANT SAFETY INFORMATION

  • There are no contraindications for TAGRISSO
  • Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of the 1142 TAGRISSO-treated patients; 0.4% 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 1142 TAGRISSO-treated patients in clinical trials, 0.9% were found to have a QTc >500 msec, and 3.6% 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 2.6% of the 1142 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 3.9% of 908 patients who had baseline and at least one follow-up LVEF assessment. 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 1142 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
  • 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 adverse reactions (≥20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue and decreased appetite

INDICATION

TAGRISSO is indicated for the first-line treatment of 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.

Please see complete Prescribing Information including Patient Information.

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