2018 ASTRO: Overall Survival With Local Consolidative Therapy in Oligometastatic NSCLC
Adding radiation therapy or surgery to systemic therapy for patients with stage IV lung cancer whose cancer has spread to a limited number of sites can significantly extend overall survival, according to new results from a multicenter, randomized, controlled phase II study. The findings were presented by Gomez et al at the 60th Annual Meeting of the American Society for Radiation Oncology (ASTRO) (Abstract LBA3).
Initial Trial Results
Researchers previously reported encouraging results for progression-free survival (PFS) from this trial, which were published by Gomez et al in The Lancet Oncology in 2016. The trial was closed prematurely, following accrual and randomization of just 49 patients. The initial results, which also included toxicity data, were for a median follow-up of 12.4 months. These initial data were limited by the absence of an overall survival (OS) endpoint, due to the short-term follow up. These new results include updated data on how long patients lived without disease progression, as well as overall survival and toxicity data for 38.8 months of patient follow-up (range, 28.3–61.4 months).
“Our hypothesis was that aggressive local therapy—radiation or surgery—would improve progression-free survival—and it did,” said Daniel Gomez, MD, Associate Medical Director of Radiation Oncology at The University of Texas MD Anderson Cancer Center. “We found that adding radiation or surgery to target all sites of disease increases the time it takes for the cancer to return or spread, and it also improves overall survival time. But the overall survival results were more impressive than anticipated.”
Study Methods
The study included patients from three hospitals (MD Anderson Cancer Center, London Health Sciences Center, and the University of Colorado) who had stage IV NSCLC and whose cancer had spread to no more than three sites. These patients received systemic therapy consisting of either four or more cycles of standard chemotherapy (platinum doublet therapy) or 3 or more months of drugs that target tumor blood vessel growth (EGFR, or ALK inhibitors for EGFR mutations/ALK rearrangements). Those whose cancers did not progress following first-line treatment were then randomly assigned to either an experimental arm in which patients were treated with surgery or radiation therapy at the tumor site (25 patients) or to a group that received standard systemic maintenance therapy and observation (24 patients).
Extended Findings
The extended follow-up data reveal that patients in the experimental arm experienced a progression-free survival benefit of 14.2 months (95% confidence interval [CI] = 7.4–24.3), compared to 4.4 months (95% CI = 2.2–8.3) for those who received standard treatment and observation (P = .014).
The difference in survival rates for the two groups was even more dramatic: patients who received radiation/surgery experienced a median overall survival rate of 41.2 months (95% CI = 18.9–NA), compared to 17.0 months (95% CI = 10.1–39.8) for those who received standard maintenance therapy/observation (P = .017).
“This is a very long overall survival time for patients with metastatic disease,” noted Dr. Gomez.
For patients treated with radiation/surgery, the time before a new lesion appeared was a median of 14.2 months (95% CI = 5.7–26.2), compared to 6.0 months for those in the standard maintenance therapy/observation arm (95% CI = 4.4–8.3) (P = .11). Neither treatment arm saw any additional severe (grade 3 or higher) toxicities than previously reported.
The newly updated results represent the first randomized data for overall survival for local ablative therapy in patients with oligometastatic NSCLC, whose cancer did not progress following front-line systemic treatment. Ongoing phase II/III trials will continue to assess the effect of local consolidative therapy (LCT) in larger populations with the addition of immunotherapy and targeted drug therapy.
“In patients with limited metastases, our study demonstrates that there is a role for more aggressive treatment,” concluded Dr. Gomez. “In fact, the patients initially treated with maintenance therapy had the option to receive surgery or radiation if their cancer spread during the trial. Exploratory analyses suggest that aggressively treating all disease sites at the time of progression improved outcomes for these patients, compared to patients who did not receive late local therapy. Thus, there may be a benefit to either early or late radiation/surgery in the setting of limited metastatic disease.”
This study was jointly funded by the MD Anderson Lung Cancer Priority Fund, MD Anderson Cancer Center Moon Shots Program, Cancer Center Support (Core), National Cancer Institute, and the National Institutes of Health.
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