For APPs & Nurses

EGFR+

Despite advancements, there are many challenges associated with treating EGFR+ mNSCLC

Disease progression is inevitable and PFS outcomes are limited1-9

Less than 20% of patients survive 5 years
About 25% to 40% of patients with EGFR+ mNSCLC never receive second-line therapy

In a survey of patients with NSCLC, patients ranked extending their lives as the most important attribute of treatment14†

MARIPOSA OS results were immature at the current analysis. As a result, no conclusions can be drawn on RYBREVANT® and LAZCLUZE™ OS benefit at this time.15

*Range includes patients who died or discontinued the assigned therapy without receiving 2L therapy during follow-up.11-13

†Data come from a cross-sectional online survey of 160 adult patients, 30 care partners, and 150 clinicians conducted between March and May 2023. Survey questions were informed by a targeted literature review, qualitative interviews, and input from a steering committee that included two lung cancer physicians, an oncology nurse practitioner, patient advocate, patient, and care partner. Descriptive statistics were generated and reported in aggregate. In addition to “extending their lives,” patients ranked “quality of life” and “functional independence” as the next most important treatment attributes.14

 

2L, second-line; EGFR, epidermal growth factor receptor; mNSCLC, metastatic non–small cell lung cancer; NSCLC, non–small cell lung cancer; OS, overall survival; PFS, progression-free survival.

EGFR+ Exon20ins

Exon 20 insertion mutations are the third most frequent EGFR mutations16

EGFR mutations chartEGFR mutations chart
Testing with next-generation sequencing (NGS) at diagnosis is critical to select the most effective first-line treatment17,18
DNA with magnifying glass
One test, multiple biomarkers17,18
Test tubes in a stand
Possibility of plasma-based CF/CT DNA testing when tissue samples are unavailable19,20
Target icon
Potential for targeted treatment18,21
Warning sign
Fewer biopsies, fewer complications17,20
Wall clock
Shorter time to test results and treatment initiation vs exclusionary and sequential testing17
Dollar sign with downward arrow
Potential lower costs for the healthcare system18,20

CF/CT DNA, cell-free/circulating tumor DNA; DNA, deoxyribonucleic acid; exon20ins, exon 20 insertion; NCCN, National Comprehensive Cancer Network.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC recommend testing patients to identify appropriate first-line treatment and to avoid therapies unlikely to provide clinical benefit22

References:

  1. Sequist LV, Yang JC-H, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-3334.
  2. Rosell R, Carcereny E, Gervais R, et al; Spanish Lung Cancer Group in collaboration with the Groupe Français de Pneumo-Cancérologie and the Associazione Italiana Oncologia Toracica. 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, randomized phase 3 trial. Lancet Oncol. 2012;13(3):239-246.
  3. Wu Y-L, 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. 
  4. Park K, Tan E-H, O’Byrne K, et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR-mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised, controlled trial. Lancet Oncol. 2016;17(5):577-589.
  5. Passaro A, Jänne PA, Mok T, Peters S. Overcoming therapy resistance in EGFR-mutant lung cancer. Nat Cancer. 2021;(2)4:377-391.
  6. Saito H, Fukuhara T, Furuya N, et al. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): an interim analysis of an open label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019;20(5):625-635.
  7. Nakagawa K, Garon EB, Seto T, et al; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced, non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669.
  8. Soria J-C, 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)(suppl appendix):1-35.
  9. Maemondo M, Inoue A, Kobayashi K, et al; North-East Japan Study Group. Gefitinib or chemotherapy for non–small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-2388.
  10. Bazhenova L, Minchom A, Viteri S, et al. Comparative clinical outcomes for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Lung Cancer. 2021;162:154-161.
  11. Nieva J, Karia PS, Okhuoya P, et al. A real-world (rw) observational study of long-term survival (LTS) and treatment patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer [ESMO abstract 1344P]. Ann Oncol. 2023;34(suppl 2):S774.
  12. Lee JY, Mai V, Garcia M, et al. Treatment patterns and outcomes of first-line osimertinib-treated advanced EGFR mutated NSCLC patients: a real-world study [IASLC abstract EP08.02-082]. Presented at: IASLC 2022 World Lung Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria.
  13. Girard N, Leighl NB, Ohe Y, et al. Mortality among EGFR-mutated advanced NSCLC patients after starting frontline osimertinib treatment: a real-world, US attrition analysis. Presented at: the European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Poster 19P.
  14. Data on file. Janssen Biotech, Inc.
  15. RYBREVANT® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
  16. Riess JW, Gandara DR, Frampton GM, et al. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC. J Thoracic Oncol. 2018;13(10):1560-1568.
  17. Pennell NA, Mutebi A, Zhou ZY, et al. Economic impact of next-generation sequencing versus single-gene testing to detect genomic alterations in metastatic non–small-cell lung cancer using a decision analytic model. JCO Precis Oncol. 2019;3:1-9.
  18. Vanderpoel J, Stevens AL, Emond B, et al. Total cost of testing for genomic alterations associated with next-generation sequencing versus polymerase chain reaction testing strategies among patients with metastatic non–small cell lung cancer. J Med Econ. 2022;25(1):457-468.
  19. 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.
  20. Pennell NA, Arcila ME, Gandara DR, West H. Biomarker testing for patients with advanced non–small cell lung cancer: real-world issues and tough choices. Am Soc Clin Oncol Educ Book. 2019;39:531-542.
  21. John A, Yang B, Shah R. Clinical impact of adherence to NCCN guidelines for biomarker testing and first-line treatment in advanced non-small cell lung cancer (aNSCLC) using real-world electronic health record data. Adv Ther. 2021;38(3):1552-1566.
  22. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed September 9, 2024. 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.