As individualized treatment approaches continue to gain momentum in the treatment of lung cancer, several specific gene mutations have been identified that contribute to the growth and spread of certain cancers. When these mutations are identified, researchers can develop medications that specifically target the effects caused by the mutations. The Epidermal Growth Factor Receptor (EGFR) mutation is common in non-small cell lung cancer (NSCLC) and should be specifically treated with precision cancer medicines that target EGFR.
Tagrisso (osimertinib) is currently the standard initial treatment for individuals with stage IB through IV NSCLC because it delays cancer recurrence and prolongs survival. All individuals with newly diagnosed lung cancer should under genomic biomarker testing with blood and tissue as soon as possible upon diagnosis.
About Tagrisso
Tagrisso (osimertinib) is a 3rd generation, EGFR- tyrosine kinase inhibitor (TKI) medication that potently and selectively inhibits both EGFRm and EGFR T790M resistance mutations. EGFR mutations occur in 30–40% of NSCLC’s in Asian populations and 10–15% in Western populations.
Tagrisso is approved by the United States Food and Drug Administration (FDA) for the treatment of EGFR + NSCLC because clinical trials have demonstrated that Tagrisso significantly delays cancer progression, prolongs survival, and is associated with fewer side effects, than standard chemotherapy for patients with stage IB-IV NSCLC.
The epidermal growth factor receptor (EGFR) 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. Tagrisso specifically targets the EGFR T790M mutation, reducing the growth and spread of the cancer cells.
Tagrisso Established as Standard of Care for Treatment of Advanced EGFRm NSCLC
The FLAURA clinical trial assessed the effectiveness and safety of Tagrisso 80mg orally once daily compared to two other widely used EGFR inhibitors; Tarceva (erlotinib) or Iressa (gefitinib) as first line therapy in 556 patients with advanced EGFRm NSCLC from Asia, Europe, and North America.
Tagrisso treated patients were reported to have a statistically-significant and clinically-meaningful improvement in progression-free survival increasing the time patients lived without disease progression or death from any cause. Updated results also confirmed that Tagrisso improves the duration of survival.1,2,4,5
- Treatment with Tagrisso improved progression-free survival by 54%.
- Average duration of response was two-fold higher for Tagrisso (17.6 months) compared to (8.7 months).
- Tagrisso improved overall survival duration compared to Tarceva and Iressa. Median overall survival was 38.6 months compared to 31.8 months with first generation EGFR-TKIs.
- More than half (54%) of Tagrisso treated patients were alive at three years compared to 44% for Tarceva or Iressa.
- Interestingly individuals of Asian ancestry did not benefit from Tagrisso relative to Tarceva or Iressa.
- Tagrisso has demonstrated activity against central nervous system (CNS) lesions – 57% of Tagrisso treated patients experienced a response.
FLAURA2
The FLAURA2 Phase III clinical trial evaluated the addition of chemotherapy to Tagrisso and found that the combination further delays cancer progression compared to treatment with Tagrisso alone in patients with locally advanced or metastatic (Stage IV) EGFRm NSCLC. The Food and Drug Administration approved Tagrisso in combination with platinum-based chemotherapy for treatment of patients with locally advanced or metastatic EGFRm NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Patients treated with Tagrisso plus platinum-based chemotherapy survived and average of 30 months with cancer progression compared to only 16.7 months for those treated with Tagrisso alone.
Although the addition of chemotherapy to Tagrisso delayed cancer progression patients do experience more side effects and many patients may benefit from Tagrisso treatment without the addition of chemotherapy. A clinical trial (SHEDDERS Trial) is currently underway to see if ctDNA can be used to determine which patients will benefit most from the addition of chemotherapy.
LAURA
The LAURA clinical trial was designed to evaluate Tagrisso in locally advanced stage III NSCLC patients unable to undergo surgery and treated with chemotherapy and radiation. The 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 platinum-based chemo-radiation therapy treatment.
Patients were treated with either Tagrisso 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. Tagrisso has been shown to delay cancer progression and prolong survival when used to treat all stages of EGFRm NSCLC.
The duration of Tagrisso treatment is unknown and clinical trials are ongoing to determine how long patients should remain in treatment. Patients in remission beyond three years should discuss the potential benefit of continued therapy with their oncologist.
ADAURA
The ADAURA clinical trial evaluated Tagrisso in surgically resected early stage NSCLC and was halted in 2020 based on determination of the effectiveness of Tagrisso in providing significant long term survival benefit for patients with EGFRm NSCLC. 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.8,9
Tagrisso in TKI Resistant NSCLC
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 Tagrisso, and the other group of patients was treated with the standard chemotherapy agents, pemetrexed plus carboplatin or cisplatin.3
- The median duration of time on treatment in which the cancer did not progress was 10.1 months for patients treated with Tagrisso, 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 Tagrisso, compared with only 4.2 months for those treated with chemotherapy.
- Serious side effects were experienced in 23% of patients treated with Tagrisso, compared with 47% of patients treated with chemotherapy.
- At 6 months following initiation of therapy, approximately 69% of patients treated with Tagrisso were alive with no progression of cancer, compared with only 37% of patients treated with chemotherapy.
The researchers concluded that Tagrisso had significantly greater efficacy than platinum therapy plus pemetrexed in patients with T790M-positive advanced NSCLC (including those with CNS metastases) in whom disease had progressed during first-line EGFR-TKI therapy.”
Tagrisso-Avastin Combination
Initial study results suggest that combination therapy with Avastin (bevacizumab) and Tagrisso (osimertinib) is well tolerated and may improve outcomes. Because the combination of Tarceva (erlotinib) and Avastin as initial treatment of EGFR-mutant lung cancers improves progression-free survival compared with Tarceva alone researchers Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College combined Avastin with Tagrisso, the current standard of care.
A total of 49 patients (median age, 60 years) with metastatic EGFR-positive lung cancers were enrolled in the interventional study between August 15, 2016, and May 15, 2018. The 12-month overall response rate was 80%, and 76% of patients survived without cancer progression. Among 6 patients with measurable central nervous system disease, all of them had a partial or complete central nervous system response.6
The most common side effects of Tagrisso treatment are diarrhea, rash, dry skin, nail toxicity, and fatigue.
Although EGFR TKIs are an effective treatment option for patients with EGFR + NSCLC, the cancer stops responding to these agents eventually. Often, the cancers will develop additional mutations that allow that cancer cells to begin growing again, despite treatment with the EGFR TKIs.
Connect With Others for Support and information
Cancer Connect was the first social network created for people with lung cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed Cancer Connect programs since 1997. Cancer Connect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating lung cancer from others. Share your experience, ask a question, or start a conversation by posting on Cancer Connect.
References:
- Abstract LBA6_PR ‘Tagrisso vs standard of care (SoC) EGFR-TKI as first-line treatment in patients with EGFR-TKI sensitising mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC): FLAURA Asian subset‘ will be presented by Byoung Chul Cho during the Mini Oral session Thoracic malignancies 2 on Sunday, 19 November 2017, 14:30 to 15:25 (SGT) in Room 310. Annals of Oncology, Volume 28, 2017 Supplement 10
- ‘Tagrisso in treatment-naïve EGFR mutation-positive advanced NSCLC (FLAURA)’ S Ramalingam et al, The New England Journal of Medicine (NEJM), 10.1056/NEJMoa1713137,
- 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 here. Accessed December 7, 2016.
- Tagrisso significantly improves overall survival in the Phase III FLAURA trial for 1st-line EGFR-mutated non-small cell lung cancer
- The primary results were presented at the ESMO Congress 2017 and subsequently published in the New England Journal of Medicine: Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:113–125. doi:10.1056/NEJMoa1713137.
- JAMA Oncol. 2020;6[7]:1-8
- Astra Zeneca press release; May 2023.
