ASCO 2016: Local Consolidative Therapy Improves Progression-Free Survival in Patients With Oligometastatic NSCLC vs Standard Chemotherapy
Lung cancer patients with oligometastases, defined as three or fewer sites of metastasis, may benefit from aggressive local therapy, surgery, or radiation, after standard chemotherapy, according to research led by The University of Texas MD Anderson Cancer Center. If validated in larger studies, the findings could represent a dramatic shift in clinical care for thousands of lung cancer patients.
Daniel Gomez, MD, Associate Professor, Radiation Oncology, presented the results at the 2016 ASCO Annual Meeting in Chicago (Abstract 9004). He and his colleagues found an 8-month progression-free survival benefit in patients treated with local consolidative therapy.
Treating Metastatic Lung Cancer
According to the American Cancer Society, 224,390 people will be diagnosed with lung cancer and 158,080 will die from the disease in the U.S. this year. Of those diagnosed, said Dr. Gomez, approximately 50% have metastatic disease, and it is estimated that about 20% to 50% present with three or fewer metastases.
Historically, explained Dr. Gomez, all metastatic lung cancer patients have been treated with chemotherapy and thought to have incurable disease. With treatment advances over the past decade, however, a number of retrospective studies have suggested that in those lung cancer patients with minimal metastases, theoretically, the disease could be better controlled long-term by local consolidative therapy.
"With recent advances in radiation delivery, targeted agents and systemic and maintenance therapy, some research has suggested it's possible to control the disease. Yet those studies have inherent bias because patients treated with local consolidative therapy were selected due to favorable risk factors," explained Dr. Gomez, the study's corresponding author.
"Our research is the first randomized prospective study of oligometastases in lung cancer to look at treating patients aggressively and comparing results to standard therapy, which typically is maintenance therapy or observation."
Study Details
The prospective phase II study was planned for 94 patients; however, because of the benefit seen in the study arm, the trial was stopped early. In total, the study enrolled and evaluated 49 patients with non–small cell lung cancer from three participating centers, with MD Anderson serving as the lead site. All patients had stage IV disease, three or fewer metastases, and no progression after initial treatment with chemotherapy. The study's primary endpoint was progression-free survival.
Half of the patients were randomized to the experimental arm of local consolidative therapy—radiation or surgical resection of all metastases, with or without chemotherapy—and the other half received standard-of-care chemotherapy. Radiation or surgery was determined by a multidisciplinary team based on metastasis presentation, and all variations of both modalities were permissible.
"With this study, we wanted to be pragmatic and allow the breadth of treatments that are now available to patients in general practice," said Dr. Gomez.
The study was powered for a 3-month progression-free survival benefit. The median progression-free survival time was 11.9 months in the local consolidative therapy arm, compared to 3.9 months in the standard therapy arm.
Seventeen patients in the standard therapy group crossed over to the local consolidative therapy arm, 14 due to progression.
Overall, of the 28 patients that progressed (12 in the local consolidative therapy arm and 16 in the standard therapy arm) 7 had progression in the primary site, 3 in a known site of metastasis, 7 in a different metastasis, and 11 in a combination of sites. Because the study was stopped early, overall survival is not yet mature.
The significance of the progression-free survival findings surprised the researchers, said Gomez.
"For some time, there's been a push from this patient population as well as a provider trend to treat with additional therapy," he said. "These findings provide evidence and enthusiasm to offer aggressive local treatment and, with validation, could pave the way to treat tens of thousands of lung cancer patients with curative intent."
Further research will report on both overall survival and quality of life, and follow up studies are being designed to include immunotherapy, making future findings more applicable to the current treatment options available to patients.
Limitations of the research include the heterogeneity of the patient population and the overall small size of the study. The study also was not powered to detect an overall survival benefit, and crossover between arms may dilute this effect.
The study was funded in part by MD Anderson’s Lung Cancer Moon Shots Program and the Lung Cancer Priority Fund.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
