Study shows surgery, radiation extend survival of patients with limited metastatic lung cancer

In first randomized trial of new approach, overall survival more than doubles to 41.2 months

Radiation or surgical removal of metastatic tumors provides a major survival advantage for lung cancer patients with minimal stage 4 disease who have not progressed after frontline chemotherapy, a study led by researchers from The University of Texas MD Anderson Cancer Center shows.

Results from a phase II clinical trial of such consolidative therapy, often thought to be futile once cancer has spread from its organ of origin to other parts of the body, are being presented at the 60th Annual Meeting of the American Society for Radiation Oncology (ASTRO) in San Antonio.

The trial, designed by MD Anderson researchers after a number of retrospective or small, single-arm studies hinted at potential impact, applied to patients with metastatic non-small cell lung cancer who had three or fewer metastatic tumors.

After receiving frontline chemotherapy or targeted therapy, patients who did not progress on those treatments were randomized to either have their metastases aggressively treated with surgery or radiation, with or without chemotherapy, or to standard-of-care chemotherapy or observation.

At 38.8 months of follow-up, the median overall survival of patients receiving the consolidative therapy was 41.2 months, compared to 17 months for those receiving standard of care.

“The overall survival difference was even larger than we expected based on our earlier findings of a significant advantage in progression-free survival,” said principal investigator Daniel Gomez, M.D., associate professor of Radiation Oncology at MD Anderson.  “Forty-one months is a survival time longer than typically observed for patients with metastatic disease.”

“These results present a strong signal for the benefit of radiation and surgery for these patients,” Gomez said. “However, particularly because the trial was initiated prior to the use of immunotherapy in lung cancer, the findings are being validated in multiple, larger clinical trials, such as the LONESTAR study at our institution.”

The original trial, planned for 94 patients with progression-free survival (PFS) as the primary endpoint, was halted early at 49 patients after a significant PFS advantage emerged during preliminary analysis.  Those results were reported in 2016, but overall survival could not be analyzed then.

The ASTRO presentation was the first to report overall survival and also updated other results.  The PFS benefit remained durable at 14.2 months in the consolidative therapy arm and 4.4 months in the standard-of-care arm. No additional grade 3 or high side effects were observed in either arm.

There was a cross-over provision to consolidative surgery or radiation for patients who progressed under standard-of-care. An exploratory analysis indicated that those patients had extended survival compared to those who remained only on systemic therapy.

“The caveat here is that fewer than half of patients appear to be eligible for consolidation at the time of progression,” Gomez said. “But these results also indicate there might be a benefit to either early or late radiation or surgery in the setting of limited metastatic disease.”

The National Cancer Institute estimates 234,030 cases of lung cancer will be diagnosed in 2018, about 13.5 percent of all cancers, and estimates 154,050 people will die from the disease, about 25.3 percent of all cancer deaths.  Lung cancer remains the leading cause of cancer deaths.  Non-small cell lung cancer accounts for about 85 percent of cases.

About half of lung cancer patients have metastatic disease at diagnosis, Gomez noted, and estimates vary of those who have three or fewer metastases at diagnosis from 20 to 50 percent.  Even at the lower estimate, consolidative treatment could apply to tens of thousands of patients.

Co-investigators with Gomez are Chad Tang, M.D., of Radiation Oncology; Jianjun Zhang, M.D., Ph.D., George Blumenschein, M.D., Ferdinandos Skoulidis, M.D., Don Gibbons, M.D., Ph.D., Anne Tsao, M.D., and John Heymach, M.D., Ph.D., all of Thoracic/Head and Neck Medical Oncology; Mike Hernandez, Rong Ye and J. Jack Lee, Ph.D., of Biostatistics; Jose Karam, M.D., of Urology; Stephen Swisher, M.D., of Surgery; Boris Sepesi, M.D., of Thoracic Surgery; Ross Camidge, M.D., Ph.D., Robert Doebele, M.D., Ph.D., Laurie Gaspar, M.D., and Brian Kavanagh, M.D., of the University of Colorado School of Medicine; and David Palma, M.D., and Alexander Louie, M.D., of London Health Sciences Center, London, Ontario, Canada.