Stereotactic radiotherapy with TKIs improves survival outcomes in lung cancer subset
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Aggressive upfront stereotactic radiotherapy along with tyrosine kinase inhibitors increased PFS and OS for certain patients with non-small cell lung cancer, according to study results presented during the ASCO20 Virtual Scientific Program.
Researchers observed the benefit, compared with TKI treatment alone, specifically among patients with EGFR-mutated oligometastatic NSCLC.
“The findings confirmed previous hypotheses of a benefit of consolidative stereotactic radiotherapy for limited metastatic NSCLC,” Xiaoshan Wang, MD, medical oncologist at Cancer Center Hospital of University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in China, said during a presentation. “It also suggests aggressive local therapy to sites at diagnosis should be explored further in large phase 3 trials as a standard treatment option in this clinical scenario.”
Data on the effectiveness of aggressive local therapy for oligometastatic NSCLC had been lacking prior to the study.
In the multi-institutional, randomized phase 3 study, Wang and colleague Ming Zeng, MD, evaluated the efficacy of upfront stereotactic radiotherapy administered to all sites at diagnosis with or without first-line TKI therapy among 133 patients with previously untreated previously untreated, EGFR-mutated oligometastatic NSCLC. All patients had stage IV disease, five or fewer metastatic disease lesions, an ECOG performance score of 2 or lower, and had no brain disease before randomization.
Researchers randomly assigned patients to first-line TKIs alone (n = 65) or TKIs in combination with upfront stereotactic radiotherapy to all sites of disease (n = 68).
PFS served as the primary endpoint. OS served as the secondary endpoint.
Median follow-up was 19.6 months (interquartile range [IQR], 9.4-41).
Results showed superior PFS among patients who received TKIs in combination with radiotherapy compared with those who received TKIs alone (median, 20.2 months vs. 12.5 months; HR = 0.61; 95% CI, 0.39-0.96). Patients who received the combination therapy also had longer OS (median, 25.5 months vs. 17.4 months; HR = 0.68; 95% CI. 0.46-1).
No patients experienced grade 5 adverse events or died as a result of treatment. Adverse events in general appeared similar between the groups. Grade 3 to grade 4 adverse events in the combination vs. TKI monotherapy groups included pneumonitis (7.3% vs. 2.9%) and esophagitis (4.4% vs. 3%)
“Adding stereotactic radiotherapy to TKI treatment was feasible and not associated with any substantial increase in the toxicity profile of treatment with TKIs alone,” Wang said during the presentation. “Although this is an investigational interim report, the finding is suggestive of value in a further exploratory study.”
Perspective
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Howard (Jack) West, MD
This is a provocative trial that has gotten less attention than it should. On its own, it’s not going to change practice, but it is one more important support and consistent note to what we have seen in previous studies with the addition of local therapy, in this case stereotactic radiosurgery to effective systemic therapy — particularly for patients with oligometastatic disease.
There have been several influential but small studies of patients with oligometastatic NSCLC that didn’t focus specifically of EGFR-mutated disease but showed impressive PFS and, sometimes, OS.
This trial looked at more than 100 patients with first-generation EGFR TKIs that did not include patients with brain metastases. In absolute terms, the results were a little disappointing in the control arm, particularly in the select population with a relatively lower volume of disease. It does, however, add one more supporting block to this consistent finding that local therapy to limited existing sites of disease with systemic therapy may lead to improvements to both PFS and OS, which changes the projection of systemic disease.
In general, we have wanted to see these studies corroborated in a multicultural, multiracial trial setting.
We definitely see that there are differences in lung cancer, as well as the behavior and risk factors for cancer in the Asian population compared with those in the United States, so it is definitely worth corroborating these results in a larger study.
Ideally, that study would look at the use of systemic therapy that is widely used in the US, such as third-generation EGFR inhibitors.
Perspective
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Jorge J. Nieva, MD
TKIs for EGFR-associated lung care are not cures, and the development of disease resistance continues to be a problem. Finding better ways to overcome drug resistance is critical as the development of new drugs for EGFR-mutated lung cancer has slowed since the approval of osimertinib (Tagrisso, AstraZeneca). A logical approach to the problem of drug resistance is the application of local consolidated therapy. The study from Wang and colleagues affirms that this patient population benefits from local consolidated therapy to a significant degree with a relatively low rate of toxicity. Although we have prior data on use of stereotactic body radiotherapy in metastatic disease, this study is important because it is larger than the landmark 2019 publication from Gomez and colleagues published in Journal of Clinical Oncology, and also because the patient population was more homogenous, limited to patients with EGFR mutations getting uniform treatment with TKIs. For this patient population, which has benefited little from the immunotherapy revolution, it is critical that we seek alternative strategies to manage disease resistance. The use of radiation therapy for oligometastatic disease is an approach that needs more widespread adoption.
Reference:
Gomez DR, et al. J Clin Oncol. 2019;doi:10.1200/JCO.19.00201.
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Wang X, et al. Abstract 9508. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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