A study of an AstraZeneca lung cancer treatment was recently stopped two years early because independent trial advisors concluded the drug, called Tagrisso, had already clearly shown a benefit over placebo. On Thursday, doctors get to see why. Results show Tagrisso reduced the risk of disease progression following surgery by 80%, a result the lead study investigator called a "home run."
The British drugmaker is now preparing to ask the Food and Drug Administration to clear Tagrisso for use in this setting, called adjuvant treatment. An approval could boost sales of the medicine, which at more than $3 billion a year is AstraZeneca's top-selling product.
Even with the dramatic result, Tagrisso likely will not have the wide impact in lung cancer that immunotherapies such as Merck & Co.'s Keytruda have had. For the trial, dubbed ADAURA, patients needed to have a specific mutation and be diagnosed early enough in their disease that surgeons could remove their tumors prior to drug treatment.
For those who qualified, however, the benefit was clear. Patients treated with Tagrisso in ADAURA were 79% less likely to have relapsed or to have died — a surrogate measure called disease-free survival — than patients taking placebo.
In more advanced patients whose cancer had spread to nearby lymph nodes, the relative risk of relapse or death was 83% lower with Tagrisso. These participants comprised the primary analysis for the study, which was unveiled Thursday ahead of the American Society of Clinical Oncology's virtual meeting.
About 30% of lung cancer patients are diagnosed in time to undergo surgery. Typically, standard treatment is post-surgical chemotherapy. But, ADAURA's lead investigator, Roy Herbst of Yale Cancer Center, said only about 5% of patients survive for five years or more following chemotherapy.
In ADAURA, even those who underwent post-surgical chemotherapy before receiving Tagrisso benefited, with results showing an 82% reduction in the risk of relapse or death versus chemotherapy followed by placebo.
The findings are "unprecedented" in lung cancer, said Tina Cascone, assistant professor in MD Anderson Cancer Center's department of thoracic/head and neck medical oncology. Cascone was not involved with ADAURA.
"What is really unprecedented for a population of patients who are potentially curable — where we only can offer a small improvement in survival with chemotherapy — we can provide, with osimertinib, an alternative strategy even after chemotherapy," she said, using Tagrisso's generic name. "And that can definitely minimize the chance of relapse and hopefully improve the chance of a cure."
Disease-free survival is not the same as overall survival, which is typically considered the most definitive measure of how beneficial a drug is. Since the trial was stopped early, there's not yet enough information to compare Tagrisso's effect on overall survival to placebo.
No new side effects to Tagrisso were observed in the trial, Herbst said. As with many targeted cancer drugs, patients taking Tagrisso experience diarrhea, rash and itching with greater frequency, which can become troublesome because treatment is taken daily for months or even years.
Tagrisso works on a type of disease called non-small cell lung cancer and, specifically, in patients whose tumors have a mutation in the epidermal growth factor receptor, or EGFR, gene, which causes abnormal proteins to be produced. EGFR-positive lung cancer is present in about 40% of patients in Asia, but is lower in Europe and the Americas.
So far, Tagrisso has been approved in EGFR-positive patients whose disease has metastasized, or spread to parts of the body outside the lung and can't be treated with surgery.
Because the population diagnosed early enough for surgery is smaller, and EGFR mutations are uncommon, about 3,000 U.S. patients a year would be eligible for post-surgical Tagrisso, said Chatrick Paul, head of AstraZeneca's U.S. oncology business, in an interview.
However, AstraZeneca has been able to earn significant sales from use of Tagrisso in a relatively small population. For example, in 2018, three years after Tagrisso's approval, just 4,600 Medicare beneficiaries received the drug, which has an annual list price of $177,000.
Tagrisso's success has fueled progressively bullish sales forecasts from Wall Street. Andrew Berens, an analyst at SVB Leerink, now predicts $16 billion in peak sales after seeing the ADAURA results. By comparison, Cowen & Co.'s Steve Scala is more conservative, but he still estimates $8 billion in sales of the drug by 2025.
In order to reach as many patients as possible, Paul said AstraZeneca will work with oncologists to expand EGFR testing. "When we have the [Food and Drug Administration] license, we are going to focus on driving the need to test all early stage non-small cell lung cancer patients for the EGFR mutation," he said.
MD Anderon's Cascone also viewed earlier testing as important. "We don't perform routine molecular testing in the early-stage population outside of a clinical trial. I think that's going to be a potentially important shift: Now we approach the molecular testing of the disease early, rather than in the metastatic setting."
Editor's note: This article has been updated to include sales forecasts from SVB Leerink and Cowen & Co.