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SAN ANTONIO -- Aggressive local consolidation in stage IV non-small lung cancer (NSCLC) drastically improved overall survival over standard care in patients with up to three metastatic lesions, a small randomized study found.

Among 49 patients whose disease had not progressed after initial systemic therapy, overall survival was 41.2 months in those treated with radiotherapy or surgery compared with 17.0 months in those on standard maintenance therapy (P=0.017), reported Daniel Gomez, MD, of MD Anderson Cancer Center in Houston, at a press briefing here at the American Society for Radiation Oncology (ASTRO) meeting.

Earlier from this study showed benefit at 12 months with this aggressive approach; the updated PFS findings, now at 38.8 months follow-up, were 14.2 months in the radiation/surgery arm versus 4.4 months in the standard arm (P=0.014). The PFS findings mirror the threefold increase seen in another NSCLC trial presented at last year's ASTRO meeting in a similar group of patients, but this is the first trial to report overall survival benefit in this setting.

In exploratory analyses, patients in the local consolidation arm were also found to have longer survival after disease progression. "This is interesting because those patients in the standard arm could have received radiation therapy or surgery at the time of progression," Gomez told 番茄社区app, suggesting that this sort of aggressive therapy is better early.

"I'm convinced that locally directed radiosurgery is beneficial for patients with low volumes of disease, and you're going to see it over and over again in all disease sites," said James B. Yu, MD, of Yale Cancer Center and Smilow Cancer Hospital in New Haven, Connecticut, adding that with SABR-COMET and now this study, he doesn't need more evidence.

"If radiation was a drug that could improve survival in the metastatic setting like that it would be millions and millions of dollars," Yu told 番茄社区app.

He added that if systemic therapy can turn a patient with distant metastases into an oligometastatic patient, then radiosurgery will be utilized even more.

"I think we're entering a new paradigm for the treatment of metastatic disease," he said. "I can see a widely metastatic patient of the future getting immunotherapy, some sort of targeted therapy, having a good response with residual disease, getting radiosurgery, and us talking about that as the routine standard of care."

ASTRO moderator Catherine Park, MD, of the University of California San Francisco, said that disease which responds to systemic therapy yet remains represents an opportunity for radiotherapy.

"I'm very excited about this study, because in a long time we haven't really imagined that we could cure stage IV disease, and I think there are many paradigms that are emerging where we're seeing an increasing relevance for locoregional treatment with the onset of more effective chemotherapies, systemic therapies, and biologics that can eradicate distant disease very effectively," she said.

From 2012 to 2016 the phase II study from Gomez's group initially set out to enroll 94 stage IV NSCLC patients with ≤3 metastatic lesions at MD Anderson Cancer Center, the London Health Sciences Center, and the University of Colorado -- enrollment was stopped by a data safety monitoring board due to the advantage seen in the investigational arm.

Following standard first-line therapy, patients in that arm received radiation or surgery to any remaining lesions and then maintenance therapy; patients in the control arm received maintenance therapy and could be treated with locoregional methods at disease progression. The primary study endpoint was PFS, and secondary endpoints included overall survival, toxicity, and time to appearance of a new lesion.

The time to appearance of a new lesion was numerically better in the local consolidation arm (14.2 versus 6.0 months, P=0.11), and no additional grade ≥3 toxicities were reported in either arm.

In subgroup analyses of the study population overall, patients with N0/N1 disease and those with no or only one metastatic site after systemic therapy appeared to derive the most benefit from aggressive treatment. The small patient population, in part a product of the decision to stop enrollment early, complicated subgroup analyses.

Inclusion criteria included patients with ECOG performance status ≤2 and no disease progression following first-line systemic treatment (platinum doublet chemotherapy or ALK/EGFR inhibitors for eligible patients). Of note, Gomez noted that one of the main study limitations was that it was conducted in the era before immunotherapy was used in lung cancer.

"The goal of this trial was not necessarily to provide the definitive answer but to really see if we could produce a strong signal," said Gomez.

"And that's why we left the trial open in several ways with regard to the eligibility criteria and the systemic therapy that a patient could receive," he continued. "We wanted to test over a broad spectrum of systemic therapy agents if adding aggressive treatment in this cohort would improve both progression-free and overall survival."

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