Tagrisso – First Precision Medicine Approved for Treatment of Early Stage NSCLC

Long-term follow up confirms Tagrisso delays cancer progression of EGFRm NSCLC and significantly prolongs survival.

Charles H. Weaver, MD
4–6 minutes
Home » Lung Cancer » Tagrisso – First Precision Medicine Approved for Treatment of Early Stage NSCLC

The ADAURA clinical trial evaluating Tagrisso (osimertinib) in surgically resected early stage non-small cell lung cancer (NSCLC) was halted in 2020 based on determination of the effectiveness of Tagrisso in providing significant long term survival benefit for patients with epidermal growth factor receptor (EGFR) mutations. Updated data presented at the 2023 ASCO Annual Meeting and simultaneously published in the New England Journal of Medicine confirm that benefit, 85% of Tagrisso treated patients survive 5 years compared to 73% of those treated with placebo establishing Tagrisso as the standard of care for early stage EGFR mutated NSCLC.13,14

The development of precision cancer medicines has allowed for more precise targeted treatment of certain cancers which can spare individuals the side effects associated with chemotherapy.  Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have epidermal growth factor receptor – mutated (EGFRm) NSCLC.3-5 These patients are particularly sensitive to treatment with precision cancer medicines known as EGFR-tyrosine kinase inhibitors (TKIs) which block the cell-signaling pathways that drive the growth of EGFR expressing lung cancer cells.

Tagrisso is a third-generation, irreversible EGFR-TKI designed to inhibit both EGFR-sensitizing and EGFR T790M-resistance mutations, with clinical activity against CNS metastases. Tagrisso is the standard of care for the treatment of EGFRm advanced NSCLC because it delays cancer progression and prolongs survival. It’s logical that it should be evaluated and demonstrate benefit in earlier stage cancers.

Surgically Resected Early Stage EGFRm NSCLC

The ADAURA clinical trial confirmed that patients with early stage (II-III) NSCLC and an EGFR mutation benefit from treatment with the targeted precision cancer medicine Tagrisso. Adjuvant Tagrisso administered following surgery for NSCLC significantly improves survival and delays cancer recurrence in patients with EGFR mutated NSCLC.1,2,13,14 All patients diagnosed with NSCLC should undergo NGS-biomarker testing for EGFR to see if they can benefit from treatment with Tagrisso. Patients should further discuss the role of chemotherapy which may provide additional benefit to treatment with Tagrisso alone. 

In the Phase III ADAURA clinical trial Tagrisso treatment for up to three years was compared to placebo as adjuvant therapy in patients with stage IB, II and IIIA EGFRm NSCLC following complete cancer resection. The trial enrolled 682 patients from more than 200 treatment centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East.

Eligible patients with resectable tumors were required to have predominantly non-squamous histology and EGFR exon 19 deletions or exon 21 L858R mutations identified via the cobas® EGFR Mutation Test.

On average patients with stage II/IIIA disease survived 66 months without cancer progression compared with 22 months for placebo.11 The five year rate of survival was 85% for Tagrisso compared with 77% for those receiving placebo.13 

5 Year Survival for Tagrisso Compared to Placebo

  • Stage IB 94% vs 88%
  • Stage II 85% vs 78%
  • Stage IIIA 85% vs 67%

Individuals with stage IA cancer may have high risk features and should discuss whether Tagrisso may be of benefit with their treating physician.

Unresectable Stage III EGFRm NSCLC

Some individuals with stage III NSCLC are unable to undergo effective surgical removal of their cancer – these individuals are treated with a combination of chemotherapy and radiation. The LAURA clinical trial was performed in 216 adult patients with locally advanced, unresectable stage III NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who had not progressed during or following definitive platinum-based chemoradiation therapy treatment. Patients were treated with either Tagrisso (Osimertinib) 80 mg orally once daily or placebo until disease progression or unacceptable side effects and directly compared. Cancer progression for Tagrisso treated patients took 39 months on average compared to 5.6 months for those not treated with Tagrisso. 

Based on the ADAURA trial results the FDA granted “Breakthrough Therapy Designation” and full approval in December 2020. “Osimertinib is the first targeted therapy to show significant survival benefit in the adjuvant setting. These findings reinforce adjuvant osimertinib as standard of care for patients with resected EGFR-mutated stage IB to IIIA NSCLC and highlight the importance of screening and EGFR mutation testing as early as possible to broaden treatment access for patients,” lead study author Roy S. Herbst, MD, PhD said in a presentation of the data.

References

  1. LUNGevity Foundation. Types of Lung Cancer. Available at https://www.lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer.
  2. The International Adjuvant Lung Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected Non-Small Cell Lung Cancer. New England Journal of Medicine. 2004;350:351-360.
  3. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12.
  4. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27.
  5. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013:66;79-89.
  6. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27.
  7. Osimertinib as adjuvant therapy in patients (pts) with stage IB–IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA.
  8. US Food and Drug Administration. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. December 18, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations. Accessed December 18, 2020.
  9. https://lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer.
  10. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations.
  11. Tsuboi M, Wu YL, Grohe C, et al. Osimertinib as adjuvant therapy in patients (pts) with resected EGFR-mutated (EGFRm) stage IB-IIIA non-small cell lung cancer (NSCLC): updated results from ADAURA. Ann Oncol. 2022;33(suppl 7):S1413-S1414. doi:10.1016/j.annonc.2022.08.047
  12. Wu Y-L, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071
  13. Herbst RS, Tsuboi M, John T, et al. Overall survival analysis from the ADAURA trial of adjuvant osimertinib in patients with resected EGFR‑mutated (EGFRm) stage IB–IIIA non-small cell lung cancer (NSCLC). J Clin Oncol. 2023;41(suppl 17):LBA3. doi:10.1200/JCO.2023.41.17_suppl.LBA3
  14. Tsuboi, M, Herbst RS, John T, et al; ADAURA Investigators. Overall survival with osimertinib in resected EGFR-Mutated NSCLC. N Engl J Med. Published online June 4, 2023. doi:10.1056/NEJMoa2304594
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