Osimertinib (Tagrisso)

Approved for the treatment of patients with metastatic epidermal growth factor receptor(EGFR) T790M mutation-positive non-small cell lung cancer as detected by an FDA approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.

Now approved for first line treatment for EGFR mutant NSCLC outperforming erlotinib and geftinib (FLAURO).

The FDA granted breakthrough therapy designation to osimertinib for the adjuvant treatment of patients with early-stage epidermal growth factor receptor-mutated non-small cell lung cancer after complete tumor resection with curative intent.
ADAURA  trial showed that osimertinib can benefit patients with epidermal growth factor receptor-EGFR-mutated non-small cell lung cancer after completion of curative intent and adjuvant chemo therapy: reduced the rate of recurrence in patients with stage II- IIIA NSCLC.
ADAURA trial-patients  with EGFR harboring mutations  with stage I B to IIIA nonsmall cell lung cancer received chemotherapy with osimertinib demonstrated increased increase disease free survival in the osimertinib group.
In stage IIa -III a NSCLC completely resected, epidermal growth factor receptor sensitizing mutations, had a disease free survival rate that was dramatically higher with the use of adjuvant osimertinib than the placebo group: osimertinib is approved for a adjuvant therapy and patients with EGFR exon 19 deletions or exon 21L858 R mutations.
With adjuvant therapy after surgery there was a reduction in distant recurrence  rate.
In patients  with stage IB- IIIA EGFR mutation positive NSCLC, the disease free survival was significantly longer among those who received Osimertinib than those who receive placebo (Wu YN).
Adjuvant osimertinib therapy for three years is standard of care for patients with resected stage IB- IIIA non-small cell lung cancer harboring EGFR common alterations.

Among patients with previously untreated advanced NSCLC with an EGFR mutation, those who receive this drug had longer overall survival in those who receive a comparative EGFR-TKI: median overall survival 38.6 months and 31.8 winds in the comparative group (Ramalingam SS).

Approval for patients with NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations.

A third generation EGFR tyrosine kinase inhibitor.

Phase III data in FLAURA trial PFS 18.9 months with a 54% reduction in risk of progression or death compared to standard therapy with erlotinib or geftinib with a PFS of 10.2 months.

An EGFR-TKI, 8 targeted medication designed to inhibit both the activating, sensitizing mutations (EGFRm) and  T790M, a genetic mutation that doubles EGFR-TKI treatment resistance.

AURA, a phase 2 study the drug was tested in T790M-positive patients after progression during treatment with first generation TKIs and had a median progression free survival of 12.3 months and the duration of response was 15.2 months in responders.

In the above study CNS lesions had a response rate of 64%.

Almost 2/3 non-small cell lung cancer patients who are EGFR mutation positive and experienced disease progression after being treated with an EGFR-TKI develop TM790 resistance.

Doses 80 mg once daily with or without food.

Most common adverse reactions are:Diarrhea, rash, dry skin, and nail toxicity.

No contraindications to use.

A once daily tablet for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.

The approval based on two multicenter, single-arm, open-label clinical trials in patients with metastatic EGFR T790M mutation-positive NSCLC who had progressed on prior systemic therapy.

Adjuvant osimertinib provides a significant overall survival benefit among patients with completely resected, EGFR mutated, stage, 1B to IIIA non-small non-small cell lung cancer (ADAURA investigators).

First line treatment with osimertinib plus chemotherapy led to significantly longer progression free survival than osimertinib  monotherapy among patients with EGFR mutated advanced NSCLC (FLAURA2 investigators).

Associated with reduced incidence of brain metastases and responses to established brain metastases.

EGFR T790M mutation-positive NSCLC as detected by the cobas® EGFR mutation test and received osimertinib 80 mg once daily.

Overall response rate 57%-61%, with duration of response of greater than 1 year.

Common adverse events were diarrhea (42%), rash (41%), dry skin (31%), nail toxicity (25%), eye disorders (18%), nausea (17%), decreased appetite (16%), and constipation (15%).

The most common serious adverse reactions were pneumonia and pulmonary embolism (2% each).

The most frequent adverse reaction leading to dose reductions or interruptions were prolonged QTc and neutropenia.

Adverse events leading to discontinuation included ILD/pneumonitis (2%), and cerebrovascular accident (1%).

Fatal adverse events occurred in 3.2% of patients, including 4 cases of pneumonitis attributed to osimertinib.

The recommended dose and schedule for osimertinib is 80 mg given orally once daily.

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