A new adjuvant therapy, osimertinib (Tagrisso), has been approved after tumor resection for adults with non-small cell lung cancer whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by a test approved by the Food and Drug Administration. It is also approved as first-line treatment for those with non-small cell lung cancer whose tumors have the same deletion or mutation. Osimertinib was previously approved as treatment for metastatic EGFR T790M mutation-positive non-small cell lung cancer. Osimertinib is a kinase inhibitor of the EGFR and it irreversibly binds to certain mutant forms of the EGFR.
Osimertinib's efficacy was demonstrated in a randomized, double-blind, placebo-controlled trial (ADAURA) of patients with non-small cell lung cancer and EGFR exon 19 deletions or exon 21 L858R mutations who had complete tumor resection, with or without prior adjuvant chemotherapy. Patients received either osimertinib or placebo following recovery from surgery and standard adjuvant chemotherapy (if given). The major efficacy outcome was disease-free survival (defined as a reduction in the risk of disease recurrence or death). There was a difference in disease-free survival with osimertinib use that was both statistically significant and clinically meaningful compared with placebo.
The efficacy of osimertinib was also measured in a randomized, double-blind, active-controlled, multicenter trial (FLAURA) in patients with EGFR exon 19 deletions or exon 21 L858R mutation-positive, metastatic non-small cell lung cancer, who hadn't received previous systemic treatment for metastatic disease. Those who received osimertinib had statistically significant improvement in overall survival compared with those who received the non-small cell lung cancer treatments erlotinib or gefitinib.
Osimertinib's labeling carries a warning that interstitial lung disease/pneumonitis occurred in 3.7% of those receiving osimertinib. The drug can also prolong the QTc interval; induce cardiomyopathy (in 3% of patients); and cause keratitis, erythema multiforme and Stevens-Johnson syndrome, cutaneous vasculitis, and embryo-fetal toxicity. The most common adverse effects, however (seen in 20% or more of patients) are leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough. Drug interactions with osimertinib and strong cytochrome P-450 (CYP) isoenzyme CYP3A inducers can occur, decreasing osimertinib levels. These drugs should be avoided if possible.
Nurses who administer osimertinib to patients who have difficulty swallowing can dissolve the tablet in 60 mL of noncarbonated water. The tablet will not dissolve completely. It should be swallowed immediately. If necessary, it can be dissolved in 15 mL of noncarbonated water, using an additional 15 mL of water to transfer the leftover particles to a syringe for administration via a nasogastric tube. The tube should be flushed with about 30 mL of water.
Nurses should educate patients on the serious potential adverse effects of osimertinib and offer advice regarding assessment of symptoms (see Table 1), directing them to call their health care provider immediately if any are noted. Serious adverse effects may require changing or modifying the osimertinib dose.
For complete prescribing information for osimertinib, see http://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208065s021lbl.pdf.