Treatment with the targeted agent Tagrisso (osimertinib) significantly delayed cancer progression, and resulted in fewer side effects, than standard chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) whose cancer had progressed following prior therapy with an epidermal growth factor receptor (EGFR) inhibitor.
Lung cancer remains the leading cause of cancer-related deaths in the United States. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, according to the type of cell within the lung from which the cancer originated.
As individualized treatment approaches continue to gain momentum in the treatment of cancer, several specific gene mutations have been identified that contribute to the growth and spread of certain cancers. Once these mutations are identified, researchers attempt to develop agents that specifically target the effects caused by the mutations.
EGFR is a type of protein that is found on the surface of many cells. It is part of a pathway involved in normal cellular growth. However, mutations within the EGFR gene can result in the production of too many EGFR proteins, and can result in unregulated spread of cancer cells.
Standard treatment for patients who have too many EGFR proteins, referred to as EGFR+ cancer, includes EGFR tyrosine kinase inhibitors (EGFR TKIs). These drugs block the growth stimulatory effects of the mutations within the EGFR pathway, and reduce the spread of cancer.
Although EGFR TKIs are an effective treatment option for patients with EGFR+ NSCLC, the cancer stops responding to these agents after approximately 9-13 months of treatment. Often, the cancers will develop additional mutations that allow that cancer cells to begin growing again, despite treatment with EGFR TKIs. One such common mutation that can develop during EGFR TKI therapy is the T790 mutation (T790M).
Osimertinib is a targeted agent that blocks the effects of T790M. It is already approved by the United States Food and Drug Administration (FDA) for the treatment of advanced EGFR+ NSCLC that has stopped responding to EGFR TKI therapy, and has the T790M.
The clinical trial included 419 patients with EGFR+ T790M-positive advanced NSCLC that has stopped responding to prior EGFR TKI therapy. One group of patients was treated with osimertinib, and the other group of patients was treated with the standard chemotherapy agents, pemetrexed plus carboplatin or cisplatin.
- The median duration of time on treatment in which the cancer did not progress was 10.1 months for patients treated with osimertinib, compared with only 4.4 months for those treated with chemotherapy.
- Among patients whose cancer had spread to the central nervous system (brain and spinal column), a difficult-to-treat population, the median duration of time on treatment in which the cancer did not progress was 8.5 months for patients treated with osimertinib, compared with only 4.2 months for those treated with chemotherapy.
- Serious side effects were experienced in 23% of patients treated with osimertinib, compared with 47% of patients treated with chemotherapy.
- At 6 months following initiation of therapy, approximately 69% of patients treated with osimertinib were alive with no progression of cancer, compared with only 37% of patients treated with chemotherapy.
The researchers concluded that “Osimertinib had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced non–small-cell lung cancer (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy.”
Reference: Mok T, Yi-Long W, Ahn M-J, et al. Osimertinib or Platinum–Pemetrexed in EGFR T790M–Positive Lung Cancer. New England Journal of Medicine. 2016. DOI: 10.1056/NEJMoa1612674. Available at: . Accessed December 7, 2016.
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