For the treatment of metastatic EGFRm NSCLC
|TEST RESULTS||NCCN RECOMMENDED TREATMENT*|
|Sensitizing EGFR mutation positive||Specific EGFR TKI preferred†|
|PD-L1 <1% and genetic alteration negative or unknown||Chemotherapy/immunotherapy preferred or chemotherapy combination‡|
EGFR TKIs are the standard of care in first-line metastatic EGFRm NSCLC2
*Refer to the NCCN Guidelines for specific treatment recommendations for each setting. Not all agents in a drug class are recommended for each setting.
†Osimertinib (preferred option) by the National Comprehensive Cancer Network® (NCCN®).1
‡Combination chemotherapy/immunotherapy is recommended by the NCCN® for patients with a performance status 0-2. For those with a performance status 3-4, best supportive care is recommended.1
There are no head-to-head trials comparing IO and EGFR TKIs in patients with EGFRm NSCLC.
No IO therapies are FDA approved for treatment-naïve metastatic EGFRm NSCLC patients, either as a single agent or in combination9-11
§KEYNOTE-189, KEYNOTE-021 Cohort G, KEYNOTE-042, KEYNOTE-024, CHECKMATE 026, CHECKMATE 227, IMpower130, 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.12-19
IIBased on 2 ex-US studies of 13,160 patients with stage IIIB or IV NSCLC, 92% of whom had stage IV disease. 7925 patients had an EGFR mutation.20,21
¶Based on a retrospective US study of patients with EGFRm NSCLC selected from the flatiron database; 961 patients were selected for this study, and 94% had stage IV disease.22
#Based on a meta-analysis of 456 multinational studies with 115,815 patients; 153 studies included patients with stage III or IV disease. 30,466 patients had an EGFR mutation.23
**Rate includes all histologies. Based on a multinational study of 642 patients, 480 of whom were tested for EGFR. 93% of patients tested for EGFR had stage IIIB or IV disease. 105 patients had an EGFR mutation.24
††Based on a review of 151 multinational studies including 33,162 patients. 9749 patients had EGFRm adenocarcinoma.25
‡‡Based on 4 multinational studies of 1334 patients with EGFRm NSCLC, 96% of whom had stage IIIB or IV disease.26-28
1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC V.5.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed June 7, 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. 2. Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(suppl 4):iv192–iv237. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. 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. 9. Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2019. 10. Opdivo [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2019. 11. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc; 2019. 12. 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.
13. 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-024). https://clinicaltrials.gov/ct2/show/NCT02220894. Accessed January 9, 2019. 14. 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. 15. Broderick JM. Frontline pembrolizumab combo improves survival in phase III NSCLC trial. OncLive website. https://www.onclive.com/web-exclusives/frontline-pembrolizumab-combo-improves-survival-in-phase-iii-nsclc-trial. Published January 16, 2018. Accessed January 9, 2019. 16. 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. 17. 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. 18. 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 January 28, 2019. 19. 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. 20. Shi Y, Au JS,Thongprasert S, et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER). J Thorac Oncol. 2014;9(2):154-162. 21. Tseng CH, Chiang CJ, Tseng JS, et al. EGFR mutation, smoking, and gender in advanced lung adenocarcinoma. Oncotarget. 2017;8(58):98384-98393. 22. Li Y, Appius A, Pattipaka T, et al. Real-world management of patients with epidermal growth factor receptor (EGFR) mutation-positive non–small-cell lung cancer in the USA. PLoS ONE. 2019;14(1):e0209709. https://doi.org/10.1371/journal.pone.0209709. 23. Zhang YL, Yuan JQ, Wang KF, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993. 24. Lopez-Chavez A, Thomas A, Evbuomwan MO, et al. EGFR mutations in Latinos from the United States and Latin America. J Glob Oncol. 2016;2(5):259-267. 25. Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res. 2015;5(9):2892-2911. 26. Wu YL, Cheng Y, Zhou X, et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017;18(11):1454-1466. 27. Yang JC, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015;16(2):141-151. 28. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239-246.
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
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
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
TAGRISSO is indicated for the treatment of 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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