Industry Insight

20 years of EGFR in NSCLC: how precision medicine helps navigate lung cancer challenges

Henar Hevia at Johnson & Johnson considers the progress that has been made in lung cancer treatment since the discovery of EGFR, including the evolving treatment paradigm, the role of precision medicine in treatment decision-making and quality of life for patients receiving targeted treatments

20 years of EGFR in NSCLC – successes and challenges in the era of precision medicine

Lung cancer is one of the most common types of cancer in the world and somatic mutations, such as in the epidermal growth factor (EGFR) gene, play a key role in its development.1 It’s been 20 years since EGFR mutations in non-small cell lung cancer (NSCLC) were first identified and published – in that time we’ve seen remarkable progress both in treatment and the rise of a precision medicine era.2,3,4 It’s a fascinating time to be working at Johnson & Johnson because we’re committed to pioneering new therapeutic advances to get in front of cancer – our vision is to eliminate cancer completely. Despite advances in research and treatments in lung cancer, an estimated 2.4 million new cases and 1.8 million deaths still make it the first most commonly diagnosed cancer and the leading cause of cancer death in 2022.5
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What have we learnt in two decades? And how should we continue our journey with EGFR targeting and precision medicine?

The discovery of EGFR mutations linked to NSCLC patients

Certain mutations in the EGFR gene can promote lung cancer progression through tumour growth and tumour invasion, contributing to metastasis and modifying the immune responses within the tumour microenvironment.6,7 Therefore, when activating EGFR mutations are present, it represents an ideal target for the treatment of several types of cancers, including NSCLC.8 In 2003, an EGFR-TKI received accelerated approval by the US Food and Drug Administration (FDA) as a monotherapy treatment for patients with locally advanced or metastatic NSCLC after failure of previous standard of care.9 Most patients with NSCLC had no response to this particular EGFR-TKI, however ~10% of patients had a rapid, often good, clinical response and were discovered to have specific mutations in the EGFR gene, which correlated with responsiveness.10

20 years of EGFR – NSCLC success alongside the emergence of resistance

Since the first publication of the sequencing of the human genome over 20 years ago, the management of NSCLC in particular has rapidly evolved over 15 years and ushered in an era of precision medicine.4,11 We’ve seen highly effective EGFR-targeted therapies for oncogene-driven NSCLC tumours and testing for targets such as ALK, ROS1, BRAF, NTRK, RET and MET is now part of treatment guidelines.12 Therapies targeted to KRAS, NRG1 and HER2 alterations are being investigated with promising results.13 EGFR-TKIs have improved patient survival and quality of life, but tumour heterogeneity means patients can rapidly develop TKI resistance.14,15 The continuous emergence of novel mutations and subsequent resistance represents a hurdle for EGFR-based therapeutics.17

EGFR testing in the era of precision medicine

EGFR testing is a critical step in the diagnosis and treatment of cancers, including NSCLC.19 Testing of sensitising EGFR mutations, BRAF V600E, as well as ALK, ROS1 and NTRK fusions, is now standard-of-care for patients with advanced NSCLC.19 While a variety of tests – for example fluorescence in situ hybridisation (FISH), immunohistochemistry (IHC), polymerase chain reaction (PCR) – may be recommended, next-generation sequencing (NGS) is the gold standard and NGS panels can provide high sensitivity across multiple variants.16 Testing can be crucial to survival and has improved prognoses for patients with NSCLC and EGFR mutations, identifying patients most likely to benefit from targeted therapies that are able to prolong progression-free survival.6
Precision medicine offers a clinically proven way to target and tailor patient treatment through EGFR-specific mutations and we will continue to emphasise its power to physicians. This way, we can unlock even more for those with lung cancer.
I’m excited to see what the next 20 years will bring.
Janssen Pharmaceutical NV, a company of Johnson & Johnson has funded the development and publication of this article, written by a Johnson & Johnson employee.
References
  1. Gao, E, Wang, Y, Fan, Gl et al. ‘Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation’ Sci Rep (2024) 14; 9223
  2. Lynch TJ, Bell DW, Sordella R et al ‘Activating mutations in the epidermal growth factor receptor underlying responsiveness of nonsmall-cell lung cancer to gefitinib’. N Engl J Med (2004) 350(21): 2129–2139
  3. Bethune, G et al. Epidermal growth factor receptor (EGFR) in lung cancer: an overview and update. J Thorac Dis. 2010 Mar; 2(1):4851
  4. The Lancet. 20 years of precision medicine in oncology. Lancet. 2021;397(10287):1781
  5. GLOBOCAN. Trachea, bronchus and lung fact sheet. Available at: https://gco.iarc.who. int/media/globocan/factsheets/cancers/15- trachea-bronchus-and-lung-fact-sheet.pdf. Last accessed May 2024
  6. Haddad et al ‘Epidermal growth factor receptor (EGFR) in the era of Precision Medicine: The tale of a perfect example of targeted therapy. A review’. Meta Gene. (2017);11:157-163
  7. Ngaha TYS, Zhilenkova AV, Essogmo FE, et al. Angiogenesis in Lung Cancer: Understanding the Roles of Growth Factors. Cancers (Basel). 2023;15(18):4648
  8. Sigismund et al. Emerging functions of EGFR in cancer. Mol Oncol. 2018;12(1):3-20
  9. Cohen MH, Williams GA, Sridhara R, ChenG, Pazdur R. FDA drug approval summary: gefitinib (ZD1839) (Iressa) tablets. Oncologist. 2003;8(4):303-306
  10. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of nonsmall-cell lung cancer to gefitinib. N Engl J Med. 2004;350(21):2129-2139
  11. Brown NA, Aisner DL, Oxnard GR. Precision Medicine in Non-Small Cell Lung Cancer: Current Standards in Pathology and Biomarker Interpretation. Am Soc Clin Oncol Educ Book. 2018;38:708-715
  12. NCCN. Non-Small Cell Lung Cancer, Version 5.2024, NCCN Clinical Practice Guidelines in Oncology
  13. Yang SR, Schultheis AM, Yu H, Mandelker D, Ladanyi M, Büttner R. Precision medicine in non-small cell lung cancer: Current applications and future directions. Semin Cancer Biol. 2022;84:184-198
  14. Lin JJ, Cardarella S, Lydon CA, Dahlberg SE, Jackman DM, Jänne PA, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol. 2016 Apr;11(4):556-65
  15. Uribe et al. EGFR in Cancer: Signalling mechanisms, drugs and acquired resistance. Cancers 2021;13(11):2748
  16. Ionescu DN, Stockley TL, Banerji S, et al. Consensus Recommendations to Optimize Testing for New Targetable Alterations in Non-Small Cell Lung Cancer. Curr Oncol. 2022;29(7):4981-4997
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Henar Hevia has more than 22 years of experience in the pharmaceutical industry and has worked at Johnson & Johnson (J&J) for over 15 years, where she has spanned many roles. She is currently senior director, EMEA therapeutic area lead, Oncology, responsible for developing the EMEA medical strategy. She leads the EMEA team ensuring coordination across the region. Her role within J&J means that she is at the forefront of breakthrough treatments and approaches that have significant potential to positively impact survival and quality of life for people with challenging cancers.

Henar holds a PhD from the Center for Applied Medical Research (CIMA). Her thesis was awarded by the Royal Academy of Doctors of Spain (La Real Academia de Doctores de España). Henar also holds an honours degree in biochemistry from the University of Navarra and a Masters from the renowned ESADE Business and Law School in Barcelona, both Spain.
CP-453377 May 2024