First Adjuvant Therapy for Common Type of Lung Cancer Granted FDA Approval

Officials with the FDA have approved osimertinib (Tagrisso; AstraZeneca) as the first adjuvant treatment for patients with non-small cell lung cancer (NSCLC) whose tumors have a specific type of genetic mutation.

Lung cancer is the most common cancer type and the leading cause of cancer-related deaths worldwide. In the U.S., approximately 229,000 adults will be diagnosed with lung cancer in 2020, of which 76% of cases will be NSCLC.

According to the FDA, approximately 20% of patients with NSCLC will have epidermal growth factor receptor (EGFR) mutations, which are mutations on a protein that causes rapid cell growth, and consequently, helps cancer spread. Although most patients who are diagnosed with NSCLC have unremovable tumors, 30% have resectable disease; thus, more than 10,000 patients nationwide each year may be candidates for osimertinib as adjuvant therapy after tumor removal.

In addition to Friday’s approval, osimertinib was approved in 2018 for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was evaluated in a randomized, double-blind, placebo-controlled trial of 682 patients with early stage NSCLC and EGFR exon 19 deletions or exon 21 L858R mutation-positive who had undergone complete tumor removal. During the trial, 339 patients received osimertinib orally once daily, and 343 received a placebo following recovery from surgery and standard adjuvant chemotherapy, if given. The main outcome measure was the amount of time it took for the cancer to come back or for death to occur from any cause (disease-free survival). In the overall trial population, patients who received osimertinib had an 80% decrease in chance of disease recurrence compared with patients who received a placebo.

The most common adverse effects of osimertinib include diarrhea, rash, musculoskeletal pain, dry skin, skin inflammation around nails, sore mouth, fatigue and cough. According to the FDA, this drug should be withheld if patients develop symptoms of interstitial lung disease, and permanently discontinued if interstitial lung disease is confirmed. Osimertinib may affect the heart’s electrical system and can also cause issues such as heart failure so periodic monitoring should be conducted. Additionally, osimertinib may also cause inflammation of the cornea, and can cause fetal harm when administered to a pregnant woman.

Osimertinib previously received Orhan Drug designation for treatment of EGFR mutation-positive NSCLC as well as Breakthrough Therapy designation for this indication.

According to Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, Friday’s new approval for osimertinib demonstrates how additional research on therapies approved in later stages of cancer can eventually improve treatment options for patients in earlier stages,

“With this approval, patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” said Pazdur, in a prepared statement.

REFERENCE

FDA Approves First Adjuvant Therapy for Most Common Type of Lung Cancer [news release]. Silver Spring, MD; December 18, 2020: FDA. Accessed December 18, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-adjuvant-therapy-most-common-type-lung-cancer