What Is Osimertinib (Tagrisso)? FDA Approval, Licensing in Türkiye and Reimbursement
| Active ingredient | Osimertinib |
| Brand name | Tagrisso |
| Class | 3rd-generation, irreversible EGFR tyrosine kinase inhibitor (TKI) |
| Category | Targeted antineoplastic agent (oral small molecule) |
| Route of administration | Oral (film-coated tablet) |
| Frequency of administration | Daily 1 time (80 mg) |
| Approved cancer indications | EGFR exon 19 deletion/L858R metastatic NSCLC (1st line, alone or with chemotherapy) · EGFR T790M-positive NSCLC (progression after a TKI) · after resection adjuvant EGFRm NSCLC (stage IB-IIIA) · unresectable stage III EGFRm NSCLC (after chemoradiotherapy) |
| FDA approved | Yes — first approval November 2015; latest expansion September 2024 (stage III, LAURA) |
| Drugs frequently used in combination | Pemetrexed + platinum-based chemotherapy (FLAURA2, 1st-line combination) |
| Manufacturer | AstraZeneca |
| Republic of Türkiye Ministry of Health license | YES |
| SGK reimbursement | PARTIAL — since 20.11.2024, only in 1st-line metastatic exon19del/L858R disease |
| Price of Tagrisso 28 tablets (1 cycle) | ~239.050 TL (June 2026; varies with exchange rates) |
| Half-life | Approximately 48 hours (2 days) |
Osimertinib, is one of the targeted agents that has achieved the broadest range of use to date in treating EGFR-mutated lung cancer. The drug began in 2015 with a narrow 2nd-line indication and, within nine years, has established a role from 1st-line to adjuvant treatment, from stage III to chemotherapy combinations at almost every stage of EGFR-mutated disease.
In this monograph, we discuss how the drug works, its FDA approval history, what the FLAURA/FLAURA2/ADAURA/LAURA trials showed, its safety profile, and licensing, pricing and partial SGK reimbursement conditions in Türkiye in detail.
EGFR (epidermal growth factor receptor) is a cell-surface receptor that normally transmits growth signals. In EGFR-mutated lung cancers (most commonly exon 19 deletion or exon 21 L858R), this receptor remains permanently "on", causing the tumor cell to proliferate continuously.
Osimertinib binds to a cysteine amino acid in the ATP-binding site of EGFR covalently and irreversibly and is a 3rd-generation tyrosine kinase inhibitor. This permanent binding enables it to target both activating mutations and the mutation conferring resistance to first-/second-generation TKIs, the T790M resistance mutation with the same molecule — the key feature distinguishing osimertinib from its predecessors.
- Selectivity: It binds mutant EGFR with much higher affinity than normal (wild-type) EGFR — one reason skin/gastrointestinal toxicity is relatively milder than with first-generation TKIs.
- Central nervous system penetration: The molecule crosses the blood–brain barrier and reaches meaningful levels in cerebrospinal fluid; this provides a particular advantage in patients with brain metastases.
- Dose–response relationship: As exposure increases, response rates and PFS rise, but so do the risks of rash, diarrhea and interstitial lung disease (ILD) — hence the standard dose has been fixed at 80 mg.
| Date | Scope of approval | Supporting evidence |
|---|---|---|
| 13 November 2015 | In EGFR T790M-positive metastatic NSCLC, progression after previous EGFR TKI treatment — accelerated approval. | AURA/AURA2 (phase 1/2) |
| 2017 | Conversion in the same indication to full approval . | AURA3 (phase 3, confirmatory) |
| April 2018 | In EGFR exon 19 deletion/L858R metastatic NSCLC, 1st line treatment as a single agent. | FLAURA |
| 18 December 2020 | After tumor resection, in stage IB-IIIA EGFRm NSCLC, adjuvant treatment. | ADAURA |
| 16 February 2024 | Together with platinum-based chemotherapy, 1st-line combination treatment. | FLAURA2 |
| 25 September 2024 | Unresectable stage III EGFRm NSCLC, in patients without progression after chemoradiotherapy. | LAURA |
Osimertinib's broad range of approvals is based on four large, complementary phase 3 trials rather than a single study. Each produced striking results at a different disease stage — in particular, the %84 reduction in progression/death risk in LAURA and the HR of 0,20 in ADAURA represent some of the largest effect sizes seen in oncology.
FLAURA2 combined osimertinib with chemotherapy, further extending PFS in the 1st line compared with osimertinib alone; this has become an option discussed particularly for patients with brain metastases or high tumor burden.
| Trial | Patient group | Comparison | Main result |
|---|---|---|---|
| FLAURA phase 3 |
EGFR exon19del/L858R metastatic NSCLC, 1st line | Osimertinib vs erlotinib/gefitinib | Median PFS 18,9 vs 10,2 months (HR 0,46). A 6,8-month improvement in median OS. Became the preferred 1st-line treatment in NCCN guidelines. |
| FLAURA2 phase 3 · n=557 |
EGFR exon19del/L858R metastatic NSCLC, 1st line | Osimertinib + chemotherapy vs osimertinib alone | Median PFS 25,5 vs 16,7 months (HR 0,62; p<0,0001) — %38 reduction in progression/death risk. Grade ≥3 adverse events were more frequent with the combination (%64 vs %27). |
| ADAURA phase 3 · n=682 |
Resected stage IB-IIIA EGFRm NSCLC, adjuvant | Osimertinib vs placebo | HR for disease-free survival 0,20 (%99,12 CI 0,14–0,30; p<0,001). Disease-free/alive at month 24: %89 vs %52. |
| LAURA phase 3 · n=216 |
Unresectable stage III EGFRm NSCLC, after chemoradiotherapy | Osimertinib vs placebo | Median PFS 39,1 vs 5,6 months (HR 0,16; p<0,001) — %84 reduction in progression/death risk. Overall survival data are not yet mature in this analysis. |
| AURA3 phase 3 |
EGFR T790M-positive NSCLC, progression after a TKI | Osimertinib vs platinum+pemetrexed | Median PFS 10,1 vs 4,4 months — confirmatory data for full approval. |
In EGFR-mutated NSCLC, osimertinib has shown survival benefit at almost every stage (adjuvant → stage III → metastatic 1st line → metastatic 1st line+chemotherapy), with consistent and usually large effect sizes; this consistency is rare among targeted therapies.
The standard dose in all indications is 80 mg, once daily orally; it can be taken with or without food. Swallow the tablet whole; do not chew or crush it. Patients who have difficulty swallowing can disperse the tablet in half a glass of still water and take it that way.
Duration of use in adjuvant treatment is limited to a maximum of 3 years (according to the ADAURA protocol). If use with strong CYP3A4 inducers is required, the dose is increased to 160 mg and 3 weeks after stopping the inducer, the standard dose (80 mg) is resumed.
- QTc prolongation (>500 ms, on at least 2 ECGs): Withhold until QTc returns to <481 ms or baseline, then restart at a reduced dose of 40 mg.
- QTc prolongation with life-threatening arrhythmia: Permanently discontinue.
- Grade ≥2 ILD/pneumonitis: Permanently discontinue (different management may apply for Grade 1 in stage III patients after chemoradiotherapy).
- Suspected SJS, EMM or TEN: Withhold if suspected; permanently discontinue if confirmed.
Absorption: After oral administration, peak plasma concentration is reached at a median of 6 hours (range 3–24 hours); no clinically meaningful interaction with food has been observed.
Distribution: It is widely distributed in tissues and crosses the blood–brain barrier, reaching meaningful levels in cerebrospinal fluid.
Metabolism: Primarily CYP3A4/5 enzymes metabolize it.
Elimination: The terminal elimination half-life is approximately 48 hours; steady state is reached in approximately 15 days. Elimination is largely through feces.
- Strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin) may substantially reduce osimertinib exposure; coadministration should generally be avoided, and if unavoidable the dose should be increased to 160 mg.
- With strong CYP3A4 inhibitors, no clinically meaningful interaction has been demonstrated.
- Other QTc-prolonging drugs: ECG and electrolyte monitoring should be intensified during coadministration.
- Cardiotoxic agents: Additional cardiac monitoring may be required with other cardiotoxic treatments because of the risk of reduced LVEF.
- As a single agent (pooled FLAURA/AURA3): Diarrhea (%47), rash (%40), nausea (%22), decreased appetite (%21) and fatigue (%17) are the most frequently reported adverse effects.
- In combination with chemotherapy (FLAURA2): Hematological laboratory abnormalities such as leukopenia (%88), thrombocytopenia (%85), neutropenia (%85) and lymphopenia (%78), as well as rash (%49), diarrhea (%43), stomatitis (%31), nail toxicity (%27) and dry skin (%24), were frequently reported.
- Alopecia, epistaxis, skin hyperpigmentation and urticaria are reported less frequently (below %10).
- Elevated creatinine may occur as a laboratory finding.
- Interstitial lung disease (ILD)/pneumonitis: Reported in %3,7–3,9 of pooled data, with %0,3–0,4 fatal cases; median time to onset is 2,7 months. Patients with new/worsening respiratory symptoms should be evaluated promptly; permanently discontinue treatment if Grade ≥2 ILD/pneumonitis develops.
- QTc prolongation: QTcF >500 ms was reported in %0,6–1,1 of patients. Baseline and periodic ECG/electrolyte monitoring is recommended for patients with risk factors.
- Cardiomyopathy: Reported in %2,6 of patients in clinical trials, with %0,1 fatal cases. An LVEF decrease of ≥%10 from baseline to below %50 was observed in %3,9 of evaluated patients. Permanently discontinue treatment in patients who develop symptomatic congestive heart failure.
- Keratitis: Patients with eye pain, redness, light sensitivity or vision changes should be referred promptly to ophthalmology.
- Severe cutaneous reactions: Erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis and cutaneous vasculitis have been reported after marketing; withhold treatment if suspected and permanently discontinue if confirmed.
- Aplastic anemia: Fatal cases have been reported.
- Pregnancy and fertility: Women, during treatment and after the last dose, for 6 weeks, while men with female partners for 4 months should use effective contraception.
The most frequently reported resistance mechanisms include loss of the T790M mutation (the disappearance of this mutation during osimertinib treatment may paradoxically indicate activation of a different resistance pathway), a new resistance mutation, EGFR C797S, KRAS mutations and c-MET gene amplification among others. Identifying these mechanisms may guide the choice of treatment after progression (e.g., a MET inhibitor combination, chemotherapy or bispecific agents); molecular profile updating by repeat biopsy or liquid biopsy (ctDNA) at progression is therefore increasingly recommended in clinical practice.
License: Tagrisso, is licensed by the Republic of Türkiye Ministry of Health and can be obtained on prescription from community pharmacies. The license covers 1st-line metastatic exon19del/L858R NSCLC, T790M-positive NSCLC (after previous EGFR TKI) and adjuvant treatment after resection.
Reimbursement: Unlike many other new oncology agents, Tagrisso has been partially covered by SGK reimbursement since 20 November 2024. However, this coverage is narrow: SGK pays only when it is used for patients with EGFR exon 19 deletion and/or exon 21 mutation-positive locally advanced or metastatic NSCLC in 1st-line treatment, until progression under these conditions.
Uses outside coverage: Adjuvant use, stage III (LAURA) use, the FLAURA2 combination regimen and, according to some sources, T790M-positive 2nd-line use may fall outside this general reimbursement coverage; in such cases patients may have to pursue legal remedies.
| Date | Price of Tagrisso 80 mg (28 tablets) (approximate) |
|---|---|
| January 2025 | 223.864,65 TL |
| June 2026 | 239.050,10 TL |
- Positivity for EGFR exon 19 deletion and/or exon 21 L858R mutation by genetic testing must have been confirmed.
- The diagnosis of locally advanced or metastatic NSCLC must be established.
- Use must be approved in a medical board (committee) report.
- Treatment must continue until progression; at the end of the report's validity period, the absence of progression must be documented in a new report.
- For uses outside SGK's general coverage, such as adjuvant treatment, stage III or a combination regimen, patients/relatives may first submit a written application to SGK.
- If the application is rejected, they may file in a labor or administrative court a lawsuit requesting an interim injunction .
- Courts, if the drug is shown to be used according to universal medical standards and to have a positive effect on survival, may, against SGK, an interim injunction issue such a ruling.
- This process requires legal support; the outcome is not guaranteed and each patient's file is assessed individually.
Who is this drug for? For patients with non-small cell lung cancer and a confirmed EGFR mutation (exon 19 deletion, L858R or T790M). Without mutation testing, this drug has no place.
How is it used? It is a tablet taken by mouth once daily, with or without food. Swallow it whole; do not chew or crush it.
What should you watch for? Immediately tell your healthcare team about a new or worsening cough, shortness of breath or fever — these may indicate a lung adverse effect. Eye pain, redness or vision changes, palpitations or feeling faint should also be reported.
Price and reimbursement in Türkiye: Tagrisso is licensed in our country and may be covered by SGK for 1st-line metastatic use — this requires your genetic test result and a medical board report. Reimbursement is limited in other settings such as adjuvant, stage III or combination use; in these cases you are advised to contact your hospital's social services unit or a healthcare law attorney.
Osimertinib is the most mature example of how targeted treatment can expand to cover every stage of a disease — from adjuvant to metastatic 1st-line treatment, from stage III to combination regimens. Supported by four large phase 3 trials over nine years, this expansion has reshaped the entire treatment algorithm for EGFR-mutated lung cancer.
LAURA (stage III, n=216): HR for PFS 0,16 — %84 reduction in progression/death risk (39,1 vs 5,6 months). ADAURA (adjuvant, n=682): HR for disease-free survival 0,20. FLAURA (1st line): PFS 18,9 vs 10,2 months, a 6,8-month improvement in OS. FLAURA2 (1st line+chemotherapy, n=557): PFS 25,5 vs 16,7 months (HR 0,62). Together, these four studies show that osimertinib offers consistent survival benefit from early to advanced EGFR-mutated disease.
In FLAURA2, the combination regimen carries substantially higher Grade ≥3 toxicity than osimertinib alone (%64 vs %27) — keeping open the question of which patients truly benefit from the combination. Overall survival data in LAURA are not yet mature. ILD/pneumonitis and cardiomyopathy risks are low but potentially fatal and require ongoing monitoring. And an important limitation specific to our country: SGK reimbursement is restricted to 1st-line metastatic use — patients can face a substantial financial burden for other indications with strong evidence, such as adjuvant and stage III use.
EGFR mutation testing (exon 19 deletion, L858R, T790M) is the starting point for treatment planning, and retesting at progression (tissue or liquid biopsy) may guide subsequent treatment selection. In patients being considered for the FLAURA2 combination, particularly those with brain metastases or high tumor burden, the potential PFS gain must be weighed against increased toxicity. When planning treatment in Türkiye, clarifying early which indication falls within SGK reimbursement coverage is important for preparing the patient's financial plan.
What will mature overall survival data from LAURA show? Can a biomarker (e.g., ctDNA clearance) identify who truly derives additional benefit from the FLAURA2 combination? Will combinations with MET inhibitors or bispecific agents become standard for patients who develop osimertinib resistance? And the most practical question for Türkiye: when will SGK reimbursement coverage expand to include adjuvant and stage III indications?
- This document contains no dose-adjustment advice and recommends no treatment regimen.
- Price and SGK reimbursement information is a snapshot and may change with exchange rates/regulatory updates; consult your pharmacist and SGK for the current status.
- SGK reimbursement varies by indication — licensing does not automatically mean that every use is reimbursed.
- Overall survival data from the LAURA trial were not yet mature when this article was prepared.
- The decision to use the drug belongs solely to the medical oncologist familiar with the patient.
- TAGRISSO (osimertinib) Prescribing Information, AstraZeneca Pharmaceuticals LP. FDA access: accessdata.fda.gov (208065s030lbl).
- Soria JC, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer (FLAURA). N Engl J Med. 2018;378:113-125.
- Planchard D, et al. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC (FLAURA2). N Engl J Med. 2023;389:1935-1948.
- Wu YL, et al. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer (ADAURA). N Engl J Med. 2020;383:1711-1723.
- Lu S, et al. Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC (LAURA). N Engl J Med. 2024;391:585-597.
- Mok TS, et al. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer (AURA3). N Engl J Med. 2017;376:629-640.
- TAGRISSO Summary of Product Characteristics (SmPC), TİTCK, Türkiye license record; SGK Health Implementation Communiqué (SUT) update, 20.11.2024.
- NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer, current version.
Editor's note: This monograph is for general information only; it is not medical advice, a diagnosis or a treatment recommendation, and does not promote any product. All reported data have been verified against primary sources and presented without direct quotation. Dose-adjustment advice has deliberately been excluded from this document; dosing information is summarized from FDA prescribing information for general educational purposes only, and treatment decisions are solely the responsibility of the treating physician. Tagrisso is licensed in Türkiye by the Republic of Türkiye Ministry of Health and has been partially covered by SGK reimbursement under certain conditions since 20 November 2024 (1st-line metastatic EGFR exon19del/L858R NSCLC); however, this coverage does not include all licensed indications and may change with regulations. As price information can vary with exchange rates and periodic drug pricing decrees, the amounts shown here are a nonbinding snapshot. Information on the legal proceedings mentioned when SGK reimbursement is unavailable is general information and does not constitute individual legal advice; consulting an attorney specializing in healthcare law is recommended. Overall survival data from the LAURA trial were not yet mature when this article was prepared, and results may be updated over time. Do not stop or change any medication without consulting your physician. Consult a physician familiar with you for every decision concerning your health.
Sources
Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer.
NEJM, 11 January 2018
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