Lung cancer remains the number 1 cause of cancer-related death in the United States. Important developments in the treatment of lung cancer were reported in September at the 2017 annual meeting of the European Society for Medical Oncology (ESMO) in Madrid, Spain. These developments have significant implications for patients with lung cancer: they include key findings from 3 clinical studies that will likely change the standard of treatment for some patients with lung cancer, as discussed below.
Potential New Drug for Stage III Lung Cancer
New results from a study reported at ESMO 2017 showed that patients with locally advanced (not metastatic), stage III non–small-cell lung cancer (NSCLC) who were unable to have surgery (unresectable cancer) and received the drug Imfinzi (durvalumab), lived more than 11 months longer without disease progression than patients who received placebo, demonstrating the benefits of this drug for these patients.
Imfinzi is a new immunotherapy known as a PD-L1 inhibitor that is currently approved for bladder cancer. In July 2017, the FDA granted Imfinzi a Breakthrough Therapy designation for locally advanced NSCLC. A Breakthrough Therapy designation is given to drugs intended to treat a serious or life-threatening condition for which preliminary clinical evidence shows the drug is substantially better than other drugs in at least one important way. The FDA then expedites the review and approval process for that drug.
The majority of patients with stage III lung cancer will not be able to have surgery and will experience disease relapse (return) despite chemotherapy, and only 15% will survive 5 years or longer. This study is the first phase 3 clinical trial that investigated a PD-L1 inhibitor in such patients.
“We saw a clear improvement in outcome versus placebo,” said Luis Paz-Ares, MD, PhD, study investigator and Chair of the Medical Oncology Department, Hospital Universitario 12 de Octubre, in Madrid, Spain, who presented the study results.
“Durvalumab is a promising new therapeutic option for patients with stage III locally advanced NSCLC,” Dr. Paz-Ares said, adding that Imfinzi extends the duration of time without disease progression by more than 11 months. “We haven’t analyzed survival data yet, but we hope we can increase the percentage of patients alive at 5 years with this therapy,” he said.
These new findings will likely expedite the complete FDA approval of Imfinzi for the treatment of lung cancer, which will add an important new treatment option to patients with locally advanced, stage III NSCLC.
Tagrisso as First-Line Therapy in Lung Cancer
The findings of another study reported at ESMO 2017 will also likely change the treatment options for patients with lung cancer that is associated with a specific EGFR genetic mutation. This study showed that Tagrisso (osimertinib) was safe and effective as the first treatment for patients with metastatic NSCLC and the EGFR T790M mutation. Tagrisso is already approved by the FDA as a second-line treatment for patients with NSCLC and EGFR T790M mutation.
The study included patients with NSCLC and the EGFR T790M mutation who have not received any previous therapy. The use of Tagrisso as first-line therapy in these patients improved the proportion of patients whose disease did not progress by 54% compared with the current first-line standard therapy, according to principal researcher Suresh Ramalingam, MD, Deputy Director, Winship Cancer Institute of Emory University, Atlanta, GA, who presented the results at the meeting.
Several EGFR inhibitors are available today, and have shown better results than chemotherapy as first-line treatment, but patients with lung cancer will eventually experience disease relapse (return) and need new treatment options. Furthermore, in many patients, the resistance to treatment is related to the T790M mutation, which may explain the good results seen with Tagrisso, which is specifically designed to block the activity of the EGFR T790M mutation.
“Osimertinib was clearly superior to standard first-line treatment in patients with EGFR-mutated NSCLC,” Dr. Ramalingam said. Furthermore, he added, “The progression-free survival benefit for patients with and without brain metastases was almost identical, suggesting that osimertinib is active in the brain, as well as in systemic sites. This is important, because brain metastasis is a common problem in EGFR-mutated patients.”
Commenting on these results, Enriqueta Felip, MD, Head of the Lung Cancer Unit, Oncology Department at Vall d’Hebron University Hospital in Barcelona, Spain, said, “Osimertinib reduced the risk of cancer progression by 54% compared with standard of care, and extended the median time to progression by about 9 months. The drug was well-tolerated, and it has activity in the brain. Based on these results, osimertinib should be considered a new first-line treatment option for patients with EGFR mutations.”
How Often Is a CT Scan Needed in Early-Stage Lung Cancer?
The current monitoring guidelines recommend that patients with NSCLC whose tumor was removed by surgery should have a physical exam and a chest CT scan every 3 to 6 months for the first 2 to 3 years after surgery. However, there is no evidence to show that such a frequent CT scan is helpful. Still, the majority of doctors continue to require a CT scan for their patients during follow-up visits.
The findings of a new study presented at ESMO 2017 call into question this practice. The study compared 2 groups of patients with early-stage lung cancer—one group had a physical exam, a chest x-ray, and a CT scan during the first 2 years after lung cancer surgery; the other group had a physical exam and a chest x-ray, but no CT scan. The results showed no significant difference in outcomes between the 2 groups.
Experts who spoke at ESMO disagreed about the meaning of this finding. Some said that survival was still better in the group that had regular CT scans, and CT scans detected second cancers better than x-ray. Still others suggest that an annual CT scan may be sufficient and may reduce the total cost of care.
“Because there is no difference between arms, both follow-up protocols are acceptable,” said the study investigator Virginie Westeel, MD, from Centre Hospitalier Régional Universitaire, Hôpital Jean Minjoz in Besançon, France. “A conservative point of view would be to do a yearly CT-scan…however, doing regular scans every 6 months may be of no value in the first 2 postoperative years,” she said.
By contrast, Dr. Felip, who also commented on this study, said, “Regular scans have a potential long-term benefit, especially in detecting second cancers. In my clinical practice, I will continue to do CT scans. I will not change my practice.”
Other doctors noted that the use of frequent CT scans for monitoring patients during the first 2 or 3 years after lung cancer surgery is not necessary, unless the patient has a known high risk for lung cancer, such as a smoking history or a genetic mutation. Patients should discuss their preferences with their doctors to come to a mutual agreement.
