The targeted therapy drug Tagrisso (osimertinib) significantly extends survival for patients with earlier-stage non-small-cell lung cancer (NSCLC) who have the EGFR mutation, according to research released May 28, 2020, from the American Society of Clinical Oncology (ASCO) Virtual Scientific Program to be held May 29 to 31.
The study, which is based on data from the phase 3 ADAURA trial, showed that giving Tagrisso to relatively early stage patients with lung cancer whose tumors were positive for the epidermal growth factor receptive–positive (EGFR) mutation dramatically increased disease-free survival time compared with patients who did not receive the drug.
Early Tagrisso Use of Tagrisso Will Become New Standard of Care
Researchers randomized 682 patients with primary nonsquamous stage 1B to 3A NSCLC and the EGFR mutation to receive Tagrisso or the standard of care chemotherapy after surgery to remove their tumors.
Among patients with stage 2 to 3A disease, the study found that 90 percent of Tagrisso patients were alive at two years without the cancer recurring compared with 44 percent of the patients who received standard-of-care treatment. Risk of disease recurrence or death was reduced by 83 percent for patients treated with Tagrisso.
The randomized controlled trial was unblinded early after an independent monitoring committee recognized the unique survival advantage in patients receiving Tagrisso.
The results are practice-changing, establishing Tagrisso, a type of drug known as a tyrosine kinase inhibitor, as front-line treatment for patients with localized NSCLC and the EGFR mutation, said lead author Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital and associate cancer center director for translational research at Yale Cancer Center in New Haven, Connecticut.
“These are extraordinary results,” said Dr. Herbst. “This was much better than expected and is certainly something that’s going to help patients.”
Tagrisso Could Be Used Before Surgery in the Future
Lung cancer is the leading cause of cancer death worldwide, and about 135,000 Americans die of the disease each year, according to the American Cancer Society. Most lung cancers are non-small-cell lung cancers. EGFR mutations occur in about 10 to 20 percent of NSCLC patients in the United States and up to 40 percent of Asian patients.
Tagrisso is already approved for patients with advanced NSCLC — cancer than has spread beyond the lung — who have the EGFR mutation. The new study focused on earlier-stage disease that is confined to the lung or nearby lymph nodes (stages 1B, 2, and 3A), which is typically described as “localized” cancer and accounts for about 60 percent of NSCLC patients.
Typically, these patients undergo chemotherapy after surgery to remove the tumor. However, recurrence rates remain high with this approach, Herbst said.
The current study demonstrated benefits in every type of patient subgroup, including gender, age, race, smoking status, and having previously received chemotherapy. Even patients with very early stage (1B) disease, which is often curable, showed a reduction in disease recurrence by receiving Tagrisso compared with those not taking the drug.
Future studies will look at whether taking Tagrisso prior to surgery for localized lung cancer is a productive approach that could lead to smaller surgeries and possibly avoid the need for chemotherapy in some patients, Herbst said.
“Why save your best drug in any disease?” he said. “Give the best drugs, the targeted drugs, as early on in the disease as possible. Drugs such as this one given to patients at the earliest possible time, can prevent those metastases and allow patients to live longer and with a better quality of life.”
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Using Immunotherapy Sooner Benefits Patients With Advanced Bladder Cancer
A practice-changing study has found that people with advanced urothelial cancer (bladder cancer) who were treated with Bavencio (avelumab) following chemotherapy experienced longer survival compared with best supportive care alone.
People with advanced bladder cancer often relapse following first-line treatment with chemotherapy. But the study shows that using Bavencio as maintenance therapy significantly extends the time before recurrence, said lead author Thomas Powles, MD, a professor of genitourinary oncology and Director of Barts Cancer Centre in London.
The therapy represents “a new first-line standard of care for advanced urothelial cancer,” he said.
Using Immunotherapy for Earlier-Stage Disease Pays Off
Bladder cancer is the sixth-leading cause of cancer death in the United States, according to the American Cancer Society. Bavencio is a type of immunotherapy drug called a checkpoint inhibitor. It works by blocking a protein on the surface of cancer cells that then allows the body’s natural immune system to identify and attack cancer cells.
Previous research showed that Bavencio was effective in prolonging survival among patients with metastatic disease. But the new study, called the JAVELIN Bladder 100 trial, shows the benefits of using the medication immediately following initial chemotherapy, as part of the first-line treatment protocol.
“Most patients respond [to chemotherapy], but unfortunately, progression-free survival and overall survival is short because resistance to platinum-based chemotherapy occurs,” Dr. Powles said. The immune checkpoint inhibitors, such as Bavencio, have been reserved as a second-line treatment after the failure of platinum-based, first-line therapy.
But very few patients survive long enough to receive a checkpoint inhibitor, he said. The new study, “gives checkpoint inhibitors directly sequenced with chemotherapy instead of waiting for the cancer to return — so it’s essentially a first-line maintenance approach.”
Bladder Cancer: A Good Fit for Checkpoint Inhibitors
The randomized, phase 2 clinical trial involved 700 patients who had responded to initial chemotherapy. The patients had inoperable tumors or metastatic disease. The patients were randomized to receive either Bavencio plus best supportive care or best supportive care alone. Supportive care includes measures to relieve pain and other symptoms, and improve quality of life.
Median overall survival with Bavencio was 21.4 months, compared with 14.3 months for best supportive care alone.
The study also showed more dramatic benefits for patients whose tumors were positive for the PD-L1 biomarker, which is commonly used as an indicator of how well a tumor will respond to a checkpoint inhibitor.
Tumors that contain many mutations within the DNA of the cancer cells, such as melanoma and lung cancer, are also generally known to respond well to checkpoint inhibitors.
“In urothelial cancer, patients have high PD-L1 expression and high tumor mutational burden,” Powles said. “This means that checkpoint inhibitors can work quite well in urothelial cancer.”
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Keytruda Helpful for a Subset of Patients With Advanced Colorectal Cancer
Data from a phase 3 clinical trial called KEYNOTE-177 found that using Keytruda (pembrolizumab) as an initial therapy in a subgroup of patients with advanced colorectal cancer doubled the time in which the cancer did not progress compared with chemotherapy.
The study represents the first time that Keytruda has been showed to benefit advanced colorectal cancer patients as a first-line therapy and has the potential to change the standard of care for treatment in the disease, said ASCO President Howard A. Burris III, MD. Dr. Burris was not involved in the study.
The patients who benefited from the drug were those with high levels of mutations, known as "microsatellite instability high," "mismatch repair deficient" mutations, which account for about 5 percent of patients.
In the study of 307 patients with this genetic mutational signature, Keytruda improved progression-free survival to 16.5 compared with 8.2 months for patients taking chemotherapy with or without targeted therapy.
Moreover, 83 percent of the patients taking Keytruda had a response to the drug lasting longer than two years, compared with 35 percent of the patients receiving chemotherapy.
“No medical treatment has shown such a difference in terms of improvement of progression-free survival in metastatic colorectal cancer,” said lead author Thierry André, MD, of the Sorbonne Université and Hôpital Saint Antoine in Paris. “Pembrolizumab should be the new standard of care for these patients. The hope is that after starting pembrolizumab, some patients are cured of metastatic disease.”
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