AstraZeneca, which already has a strong presence in lung cancer, is poised to deepen its reach in the disease with clinical data that support expanding the use of two of its approved therapies in ways that clinicians say will change the standard of care for many patients.
The data are set for presentation Sunday during the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. First up is the targeted therapy osimertinib, which is marketed under the brand name Tagrisso. The small molecule blocks mutated forms of the EGFR protein, which drives cancer growth. The drug is already approved for use as a first-line treatment for non-small cell lung cancer (NSCLC) positive for EGFR mutations. It’s also used for advanced cases of such cancers. The latest results are from a placebo-controlled Phase 3 test that enrolled patients whose EGFR-mutated NSCLC had reached stage 3 and cannot be removed surgically.
Dr. Suresh Ramalingam, executive director of Winship Cancer Institute of Emory University and the principal investigator of the study, said the standard of care for patients who have reached this advanced stage is chemotherapy and radiation together, followed by treatment with the AstraZeneca immunotherapy durvalumab, marketed as Imfinzi. Speaking during a briefing with journalists in advance of the ASCO presentation, he added that prior clinical data for this treatment regimen had been unclear as to whether patients with advanced NSCLC with EGFR mutations can benefit from treatment with Tagrisso. The new clinical data indicate that they do.
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The global Phase 3 study, named LAURA, enrolled more than 200 patients with unresectable stage 3 NSCLC positive for EGFR mutations. These patients did not have any disease progression during or after receiving chemoradiotherapy. Participants were randomly assigned on a two-to-one basis to receive Tagrisso or a placebo. Study participants who received the placebo later crossed over to receive Tagrisso.
Treatment with Tagrisso led to a median 39 months of progression-free survival compared to 6 months in the placebo group, results that are statistically significant. In the study drug arm, 74% of participants did not have any cancer growth after 12 months and 65% did not have any cancer growth after 24 months, compared with 22% and 13% in the placebo group, respectively. NSCLC often spreads to the brain. Ramalingam said the results show the incidence of this metastasis was much lower for the study drug arm.
“Based on these results, osimertinib will become the new standard of care for patients with locally advanced non-small cell lung cancer following definitive chemoradiation, and EGFR mutation testing should be conducted for patients with stage 3 disease in order for patient to achieve optimal outcomes,” Ramalingam said.
Dr. David Spigel, chief scientific officer of the Sarah Cannon Research Institute and the ASCO expert asked to comment on the data, called the results “outstanding.” When NSCLC progresses, patients don’t always get the chance to receive the next line of therapy, he explained. A treatment that reduces the chance of cancer growing after chemoradiotherapy will benefit them.
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“This will be practice changing, starting as soon as this becomes available, the label gets expanded, this will be how patients are treated wherever they can get access to this drug,” Spigel said.
Imfinzi Helps Patients With Limited-Stage Small Cell Lung Cancer Live Longer
Spigel is also the presenter for interim Phase 3 results of another AstraZeneca drug, durvalumab, marketed as Imfinzi. Approval of this drug, part of the class of immunotherapies called checkpoint inhibitors, includes extensive-stage small cell lung cancer. The latest results are from the Phase 3 ADRIATIC study in limited-stage small cell lung cancer (LS-SCLC), which is disease that has not metastasized. There haven’t been any major advances for this type of cancer for several decades, Spigel said. The standard of care is chemoradiotherapy, but most patients relapse within two years. Few survive beyond five years.
Durvaluamab is an antibody that blocks the checkpoint protein PD-L1. ADRIATIC tested the drug in combination with tremelimumab, a CTLA-4-blocking antibody drug that AstraZeneca markets under the name Imjudo. The Phase 3 study enrolled 730 patients who had completed chemoradiotherapy for their LS-SCLC. An interim analysis show that as of a Jan. 15, 2024, the median overall survival was about 56 months in those who received durvalumab and 33 months in those who received a placebo. Median progression-free survival was about 17 months in the study drug group and 9 months in the placebo arm. The 36-month overall survival rate was about 57% in the durvalumab group and 48% in the placebo group. At 24 months, the progression-free survival rate was about 46% in the durvalumab group and 34% in the placebo arm.
The treatment was well tolerated and safety signals are consistent with what’s known about the drugs, Spigel said. He added that this drug combination should become the new standard of care for LS-SCLC patients following chemoradiotherapy.
Dr. Lauren Byers, a professor in the department of thoracic-head and neck medical oncology at MD Anderson Cancer Center and the ASCO expert who commented on the data, called the ADRIATIC trial a landmark study. The overall survival improvement of about two years stands in contrast to many SCLC clinical trials, where the benefit is often measured only in months, she said. The results support use of the treatment regimen as a new standard of care. However, Byers added that SCLCs are different types of lung cancer. Next steps include trying to understand who benefits most from treatment with durvalumab and how to personalize a treatment depending on subtypes of SCLC.
AstraZeneca touts the results as showing Imfinzi to be the first and only immunotherapy to show survival benefit in LS-SCLC in a pivotal clinical trial. Susan Galbraith, the company’s executive vice president, oncology R&D, said in a prepared statement that the company will work with regulatory authorities to bring Imfinzi to these patients as quickly as possible. Imfinzi generated about $4.2 billion in revenue last year, an increase of about 52%, according to AstraZeneca’s annual report. Tagrisso is AstraZeneca’s top seller, accounting for nearly $5.8 billion in revenue in 2023, up about 7% from sales in the prior year.
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