TAGRISSO® (osimertinib) US approval for unresectable Stage III EGFR-mutated lung cancer

AstraZeneca has announced that its drug, TAGRISSO® (osimertinib), has received approval in the United States for treating adult patients with unresectable, Stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). This approval is significant for patients whose disease has not advanced during or after concurrent or sequential platinum-based chemoradiation therapy (CRT). The drug is specifically indicated for patients who have exon 19 deletions or exon 21 (L858R) mutations, as confirmed by an FDA-approved test.

The FDA's decision followed a Priority Review based on the results from the LAURA Phase III trial. These results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine. In the trial, TAGRISSO demonstrated a substantial reduction in the risk of disease progression or death by 84% compared to a placebo. The hazard ratio was 0.16, with a confidence interval of 0.10-0.24 and a p-value of less than 0.001. The median progression-free survival (PFS) for patients treated with TAGRISSO was 39.1 months, compared to 5.6 months for those on placebo. Overall survival (OS) data remain immature, and the trial is ongoing to further assess this secondary endpoint.

Lung cancer affects over 200,000 people annually in the United States, with 80-85% of these cases being NSCLC, the most prevalent form of lung cancer. Approximately 15% of NSCLC patients in the U.S. have EGFR mutations, and nearly 20% of NSCLC diagnoses involve unresectable tumors.

Dr. Suresh Ramalingam, Executive Director of Winship Cancer Institute of Emory University and a principal investigator in the LAURA trial, highlighted the trial's significance. He noted that patients with Stage III, EGFR-mutated lung cancer treated with TAGRISSO experienced more than three years without disease progression. This underscores the importance of early diagnosis and testing.

Dave Fredrickson, Executive Vice President of the Oncology Business Unit at AstraZeneca, emphasized the importance of TAGRISSO's approval for patients with unresectable EGFR-mutated NSCLC. He noted that these patients now have access to targeted therapy for the first time, which can serve as a foundational treatment for the disease.

The safety profile of TAGRISSO in the LAURA trial was consistent with previous studies, with no new safety issues identified. TAGRISSO is already approved for various stages of EGFR-mutated NSCLC, including as a monotherapy in the first-line metastatic setting, in combination with chemotherapy, and as an adjuvant treatment for early-stage disease. The drug is also under review by regulatory authorities in other countries for this specific indication.

Regarding safety, TAGRISSO has no contraindications but can cause severe and sometimes fatal interstitial lung disease (ILD)/pneumonitis. In studies, a small percentage of patients experienced ILD/pneumonitis, with some cases being fatal. Additionally, TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation and cardiomyopathy, including heart failure. These conditions necessitate regular monitoring and potential discontinuation of the drug in affected patients. Other potential severe side effects include keratitis, erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), cutaneous vasculitis, and aplastic anemia.

Patients should undergo a complete blood count with differential before starting TAGRISSO and regularly during treatment. Women of reproductive potential are advised to use effective contraception and avoid breastfeeding during treatment and for a specified period afterward. Common side effects include leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, and fatigue.

TAGRISSO is indicated for various stages of NSCLC, including adjuvant therapy after tumor resection, treatment of unresectable Stage III NSCLC, and first-line treatment for metastatic NSCLC with specific EGFR mutations. It's also used in combination with chemotherapy for advanced NSCLC and for treating metastatic EGFR T790M mutation-positive NSCLC that has progressed after previous EGFR-TKI therapy.