Lung cancer continues to be the number one cause of deaths related to cancer in the United States in men and women. This may explain the explosion in new drugs that have become available recently or are in development for different types of lung cancer.
In 2018, important new findings in lung cancer treatment were reported at the annual meeting of the European Society for Medical Oncology (ESMO) in Munich, Germany, and the International Association for the Study of Lung Cancer in Toronto, Canada. Below are key findings presented at these meetings.
Alunbrig Extends Disease-Free Survival in Advanced Lung Cancer with ALK Mutation
Alunbrig (brigatinib), a new generation ALK inhibitor, has shown promising results in patients with non–small-cell lung cancer (NSCLC) and ALK mutation (genetic alteration or rearrangement). Alunbrig was approved by the FDA in 2017 for patients with advanced NSCLC and ALK mutation whose cancer did not respond to Xalkori (crizotinib), an older ALK inhibitor that is the standard first treatment (first-line therapy) used in patients with advanced NSCLC and an ALK mutation.
“Brigatinib is a promising new treatment for inhibitor-naïve ALK-rearranged NSCLC.”
—D. Ross Camidge, MD, PhD
In the recent clinical trial called ALTA-1L, researchers compared the benefit of using Alunbrig instead of Xalkori as the first treatment in patients with this type of lung cancer who had not received any ALK inhibitor before.
The study results were presented at ESMO 2018, showing that patients who received Alunbrig had a longer survival period without disease progression than patients who received Xalkori. D. Ross Camidge, MD, PhD, Chair in Lung Cancer Research, University of Colorado Cancer Center, Aurora, presented the results.
The average time of survival without disease progression was 11 months with Alunbrig and 9.3 months with Xalkori. After 1 year of therapy, about two-thirds (67%) of the patients who received Alunbrig had no disease progression compared with less than half (43%) of the patients who received Xalkori. After their lung cancer progressed, 35 patients moved from the Xalkori group to the Alunbrig group.
“Brigatinib is a promising new treatment for inhibitor-naïve ALK-rearranged NSCLC. Brigatinib…is the only ALK inhibitor to demonstrate activity against multiple EGFR-mutant cell lines, and it has central nervous system penetration,” Dr. Camidge said. “In this first report of the ALTA-1L trial, brigatinib demonstrated the longest post-crizotinib progression-free survival of any ALK inhibitor in NSCLC,” he added.
In addition, in patients with lung cancer, the cancer often spreads (metastasizes) to the brain, so the researchers looked at the impact of these 2 drugs on brain metastases (or central nervous system disease).
Among patients whose lung cancer spread to the brain, the brain metastases responded to treatment in 78% of patients receiving Alunbrig versus only 29% of patients receiving Xalkori, demonstrating the ability of Alunbrig to treat the cancerous brain lesions.
Potential New Drug for Lung Cancer with ROS1 Mutation
Entrectinib is a new targeted therapy, a selective tyrosine kinase inhibitor, currently in development for patients with NSCLC and ROS1 mutation (gene alteration). Results of a new analysis of several studies with this drug were presented at the 2018 International Association for the Study of Lung Cancer. Robert C. Doebele, MD, PhD, Director, Thoracic Oncology Research Initiative, University of Colorado Cancer Center, Aurora, presented the results.
This study compared the benefit of entrectinib and the older targeted therapy Xalkori (crizotinib) in patients with NSCLC and ROS1 mutation. In some of the patients, the cancer had also spread to the brain (brain metastases). Xalkori is used as the first treatment in patients with NSCLC and ROS1 mutation. In this analysis, more patients responded to entrectinib therapy than to Xalkori, and their responses lasted longer.
“The data look very exciting. Clinically meaningful, deep, and durable responses were observed, including in patients with baseline brain metastases. The hope is that entrectinib can replace crizotinib as a first-line therapy against ROS1-positive NSCLC,” Dr. Doebele said.
“The data look very exciting….The hope is that entrectinib can replace crizotinib as a first-line therapy against ROS1-positive NSCLC.”
—Robert C. Doebele, MD, PhD
Lung cancer with ROS1 mutation affects about 1% to 2% of patients with NSCLC. Entrectinib is an oral inhibitor of several mutations and is more potent than Xalkori. It also works better on brain metastases. Brain metastasis is the most common site of cancer progression in patients with NSCLC and ROS1 mutation. About 50% of patients whose cancer progresses with Xalkori have brain metastases.
“We believe patients with ROS1-positive NSCLC may benefit from more potent ROS1 inhibitors that are central nervous system–penetrant, such as entrectinib, in the first-line setting,” said Dr. Doebele.
Imfinzi Improves Survival in Stage III Unresectable Lung Cancer
Imfinzi (durvalumab), an immunotherapy and a PD-L1 inhibitor, was approved in 2017 for patients with stage III NSCLC. Results of a new clinical trial now show that Imfinzi improves overall survival in patients with advanced, stage III NSCLC that can’t be removed by surgery (unresectable).
Imfinzi improved overall survival by 32% versus placebo in patients whose disease had not progressed after chemotherapy and radiation. Only up to one-third (15% to 30%) of patients with locally advanced, unresectable stage III NSCLC are cured with conventional chemotherapy and radiotherapy. Overall survival was significantly longer with Imfinzi versus placebo, suggesting that Imfinzi may soon be a new standard of treatment for patients with advanced, stage III, unresectable NSCLC.
The results of the trial were reported at the 2018 International Association for the Study of Lung Cancer in Toronto, Canada, by Scott J. Antonia, MD, PhD, Chair, Thoracic Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
“We saw improvements in progression-free survival, time to distant metastases, and emergence of new lesions with durvalumab, and the drug was well-tolerated. This is the first study in many years to support a survival advantage for unresectable stage III NSCLC with no progression following chemoradiotherapy,” Dr. Antonia said, adding that this study provides “a new standard of care.”
“This is the first study in many years to support a survival advantage for unresectable stage III NSCLC.”
—Scott J. Antonia, MD, PhD
By 1 year, about 83% of patients receiving Imfinzi were alive versus 75% who received placebo; by 2 years, the difference was about 66% with Imfinzi versus 55% with placebo. In addition, it took about 28 months for the cancer to spread with Imfinzi therapy versus 16 months with placebo. As can be expected, more serious side effects were reported with the immunotherapy than with placebo.
Immunotherapy Added to Chemotherapy Prolongs Survival in Small-Cell Lung Cancer
Although many new targeted therapies and immunotherapies have recently become available for patients with NSCLC, those with small-cell lung cancer have not seen new treatment options in the past 2 decades. But this is finally about to change.
The first immunotherapy, Opdivo (nivolumab), was recently approved for small-cell lung cancer. And results presented at the 2018 International Association for the Study of Lung Cancer meeting showed that adding the immunotherapy Tecentriq (atezolizumab), a PD-L1 inhibitor, to chemotherapy with carboplatin and etoposide represent a new standard of treatment as the first treatment for extensive-stage small-cell lung cancer.
Small-cell lung cancer is either limited to the affected lung or is called “extensive-stage lung cancer” when the cancer has spread outside of the lung. Stephen V. Liu, MD, Assistant Professor, Division of Hematology and Oncology, Georgetown University, Washington, DC, presented the results at the meeting.
“IMpower133 is the first trial in more than 20 years to show a clinically meaningful improvement in overall survival compared with the current standard of care in first-line extensive-stage small-cell lung cancer,” Dr. Liu said. “These findings suggest that atezolizumab plus carboplatin and etoposide represents a new first-line treatment for extensive-stage small-cell lung cancer.”
Tecentriq plus chemotherapy improved overall survival and time without disease progression in patients with extensive-stage small-cell lung cancer. The average survival was about 12 months with Tecentriq and 10 months with placebo, and the time without disease progression was about 5 months with Tecentriq and 4 months with placebo.
Although the response rates were similar in the 2 groups, the duration of response was about 3 times longer with atezolizu-mab than with placebo.
