by Dr. C.H. Weaver M.D. 8/2020

Early assessment from an Independent Data Monitoring Committee has recommended a pivotal clinical trial evaluating Tagrisso (osimertinib) in early stage non-small cell lung cancer (NSCLC) be halted based of its determination of the effectiveness of Tagrisso to delay cancer progression.

Clinical trials have demonstrated that chemotherapy delays cancer recurrence and prolongs survival when used to treat early stage NSCLC. The development of precision cancer medicines has allowed for more precise targeting of certain cancers which can spare individuals that won’t benefit from treatment the side effects associated with chemotherapy. Now there is evidence that certain patients with early stage NSCLC can avoid chemotherapy and be treated with a targeted precision cancer medicine. Treatment with Tagrisso following surgery for NSCLC with an epidermal growth factor receptor (EGFR) mutation has been demonstrated to significantly improved disease-free survival in a phase III study. (1,2)

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. (3,4,5) 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.

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.

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The risk of disease recurrence or death was reduced by 79% compared to placebo and 90% of individuals treated with Tagrisso survived two years without their cancer recurring, compared to only 44% who received a placebo.

Based on the ADAURA trial results the FDA granted "Breakthrough Therapy Designation" in July and full approval in December 2020. Tagrisso should be considered the "standard of care" for stage IB-IIIA EGFRm NSCLC patients.

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.

https://lungevity.org/about-lung-cancer/lung-cancer-101/types-of-lung-cancer.

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations.