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

MedMaven

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 therapy. 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 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 of patients with Stage IB, II and IIIA EGFRm NSCLC following complete cancer resection. The trial enrolled patients from more than 200 treatment centers across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East.

Overall 682 patients were treated with Tagrisso or a placebo and directly compared. The risk of disease recurrence or death was reduced by 79% compared to placebo and 90% survived two years without their cancer recurring, compared to only 44% who received a placebo.

Adjuvant chemotherapy is the standard of care in patients with stage II-III NSCLC who have undergone complete tumor resection and select patients with stage IB disease; however, recurrence rates are high. Tagrisso is a third-generation EGFR tyrosine kinase inhibitor approved for the treatment of patients with metastatic NSCLC with tumors that have EGFR mutations (exon 19 deletions or exon 21 L858R mutations).

Based on the ADAURA trial results the FDA granted "Breakthrough Therapy Designation" in July 2020. In the trial Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival in the adjuvant treatment of Stage IB-IIIA EGFRm NSCLC patients, reducing the risk of disease recurrence or death by 79%. An Independent Data Monitoring Committee recommended for the trial to be unblinded two years early based on its determination of overwhelming efficacy.

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