Osimertinib

TAGRISSO is a kinase inhibitor indicated for: • adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. • the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. • the first-line treatment of adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

Osimertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletions) at approximately 9-fold lower concentrations than wild-type. Two pharmacologically-active metabolites (AZ7550 and AZ5104 circulating at approximately 10% of the parent) with similar inhibitory profiles to osimertinib have been identified in the plasma after oral administration of osimertinib. AZ7550 showed a similar potency to osimertinib, while AZ5104 showed greater potency against exon 19 deletion and T790M mutants (approximately 8-fold) and wild-type (approximately 15-fold) EGFR. In vitro, osimertinib also inhibited the activity of HER2, HER3, HER4, ACK1, and BLK at clinically relevant concentrations.

Adjuvant treatment of early-stage NSCLC: 80 mg orally once daily, with or without food, until disease recurrence, or unacceptable toxicity, or for up to 3 years. Locally advanced, unresectable (stage III) NSCLC: Following platinum-based chemoradiation therapy, 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. Metastatic NSCLC: 80 mg orally once daily, with or without food, until disease progression or unacceptable toxicity. Locally advanced or metastatic NSCLC: 80 mg orally once daily administered in combination with pemetrexed and platinum-based chemotherapy, with or without food, until disease progression or unacceptable toxicity due to TAGRISSO.

None. None.

• Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. For patients receiving TAGRISSO who have not received recent definite platinum-based chemoradiation therapy, permanently discontinue TAGRISSO in patients diagnosed with ILD/Pneumonitis. For patients who received recent definitive platinum-based chemoradiation therapy with Grade 1 ILD/pneumonitis continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis. • QTc Interval Prolongation: Monitor electrocardiograms and electrolytes in patients who have a history or predisposition for QTc prolongation, or those who are taking medications that are known to prolong the QTc interval. Withhold, then restart at a reduced dose or permanently discontinue TAGRISSO based on severity.

The following adverse reactions are discussed in greater detail in other sections of the labeling: • Interstitial Lung Disease/Pneumonitis • QTc Interval Prolongation • Cardiomyopathy • Keratitis • Erythema multiforme, Stevens-Johnson syndrome, and Toxic epidermal necrolysis • Cutaneous Vasculitis • Aplastic Anemia • Myalgia or Myositis with Creatine Phosphokinase Elevation Most common (≥20%) adverse reactions, including laboratory abnormalities, were: • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue. • TAGRISSO monotherapy following platinum-based chemoradiation therapy: lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough and COVID-19.

Strong CYP3A Inducers: Avoid concomitant use. If not possible, increase TAGRISSO to 160 mg daily in patients receiving a strong CYP3A4 inducer.

Store TAGRISSO bottles at 25°C (77°F). Excursions permitted to 15-30°C (59-86°F).