The addition of stereotactic body radiation therapy (SBRT) to tyrosine kinase inhibitor (TKI) therapy yielded longer progression-free survival (PFS) and overall survival (OS) than TKI therapy alone in patients with EGFR-mutant oligometastatic non–small cell lung cancer (NSCLC), according to an interim analysis of an open-label phase III trial presented during the ASCO20 Virtual Scientific Program (Abstract 9508).
There is a rationale for the use of aggressive local therapy in oligometastatic disease. Progression most frequently occurs at the site of original disease, and treatment may prevent further dissemination, according to Xiao-shan Wang, MD, PhD, of the Cancer Center Hospital of University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu, China, who presented the results.
The new randomized, open-label SINDAS trial included 133 patients with oligometastatic NSCLC; patients were included if they had a maximum of two metastatic lesions in any one organ (patients with brain metastases were excluded) and no more than five lesions total. They were randomly assigned to receive either SBRT (25-40 Gy in five fractions) plus a TKI (68 patients) or a TKI without SBRT (65 patients); TKIs included either gefitinib, erlotinib, or icotinib.
Most patients were female (63% of SBRT group and 60% of TKI-alone group), and the median age was 66.9 in the SBRT group and 63.32 in the TKI-alone group. There were similar numbers of patients with ECOG Performance Status of 0 and 1. Most EGFR mutations were exon 19 deletions (66% of the SBRT group and 72% of the TKI-alone group). Most patients had one to two total metastases (56% of the SBRT group and 62% of the TKI-alone group). Gefitinib and erlotinib were given most frequently, with less than 10% of each group receiving icotinib.
The addition of SBRT resulted in significantly improved PFS and OS. The median PFS with SBRT was 20.2 months, compared with 12.5 months without it, for a hazard ratio (HR) of 0.618 (95% CI [0.394, 0.969]; p < 0.001). For OS, the median with and without SBRT was 25.5 months and 17.4 months, respectively, for a HR of 0.682 (95% CI [0.456, 1.001]; p < 0.001).
On a multivariate analysis, ECOG score, number of metastatic lesions, and treatment with SBRT were also significantly associated with PFS. For OS, those factors as well as T stage and specific type of EGFR mutation were also significantly associated.
There were no significant differences between the groups with regard to the incidence of grade 3 adverse events. There were numerically more cases of pneumonitis in the SBRT group (30% vs. 15%; p = 0.338), and more cases of skin rash in the TKI-alone group (62% vs. 50%; p = 0.423). Grade 3 esophagitis occurred in 15% of both groups.
“This randomized phase III study measuring upfront radiation to sites of diagnosis [showed] the improvement of both PFS and OS, with equivalent toxicity, in [patients with] EGFR-mutant oligometastatic [disease],” Dr. Wang said. “The findings confirmed previous hypotheses of a benefit of consolidative SBRT for limited metastatic NSCLC.” She noted that the results are limited by the relatively small sample size, but she said that the findings suggest that the treatment should be explored in further large phase III trials.
“The findings confirmed previous hypotheses of a benefit of consolidative SBRT for limited metastatic NSCLC.” – Dr. Xiao-shan Wang
Rachel E. Sanborn, MD, of Earle A. Chiles Research Institute and Providence Cancer Institute, was the discussant for the study. She noted that there was an imbalance in the baseline characteristics that could have had an effect on outcomes, in particular with regard to specific types of EGFR mutations and choice of TKI.
“The exon 20 insertion balance could have negatively impacted the outcomes in the TKI-alone arm,” she said; 12% of the TKI-alone group had exon 20 insertions, compared with 4% of the SBRT group. Dr. Sanborn also noted that no information was available on second-line therapy, which limits interpretation of the results.
“Despite this, the data [are] compelling for the consideration of a TKI and SBRT,” Dr. Sanborn said. “When we compare with surgery for oligometastatic disease, SBRT is certainly less invasive.”
— Dave Levitan
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