Large, well designed trial has limitations
TORONTO – Prophylactic cranial irradiation, which is standard-of-care practice in patients with small cell lung cancer, also appears to improve intracranial progression-free survival (iPFS) and overall survival in patients with stage IV non–small cell lung cancer (NSCLC), according to findings from a randomized study.
The cumulative incidence of brain metastases at 2 years was 22% in 41 patients who received prophylactic cranial irradiation (PCI), compared with 52% in 43 patients who received standard care with first- and second-generation tyrosine kinase inhibitors (TKIs) without PCI, Oscar Arrieta, MD, reported at the World Conference on Lung Cancer.
PCI was associated with lower odds of progression to the CNS (odds ratio, 0.16), Dr. Arrieta, of the National Cancer Institute of Mexico, Mexico City, said at the meeting sponsored by the International Association for the Study of Lung Cancer. Further, the relative risk for iPFS in patients with an epithelial growth factor receptor (EGFR) or anaplastic lymphoma kinase mutation (ALK), who comprised 70% of patients in both groups, was 0.29 with PCI.
Median overall survival in the groups was 42.8 months versus 25.9 months (HR, 0.48).
The burden of brain metastases can impact the quality and length of survival in patients with NSCLC, and because of an aging population and advances in detection and treatment of primary cancers, patients are living longer and thus are more likely to experience brain metastases, Dr. Arrieta said, noting that this is particularly true for patients at high risk, such as those with elevated carcinoembryonic antigen levels.
Although PCI is standard in small cell lung cancer, its role in NSCLC remains controversial because of concerns about neurologic morbidity and lack of overall survival benefit, he explained.
“The objective of this study was to determine if the use of PCI reduced the development of brain metastases and improved the survival in this population without impairing quality of life,” he said.
Study participants were patients with confirmed stage IV NSCLC and adenocarcinoma histology at high risk for developing brain metastasis. PCI in the treatment group was delivered at 25 Gy/10 fractions.
The findings suggest that in NSCLC with a high risk of developing brain metastases who are treated with a first- or second-generation TKI – particularly those with EGFR and ALK mutations – PCI increases iPFS, Dr. Arrieta said.
“The findings can be extrapolated to those treated with third-generation TKIs, which have higher CNS penetration,” he said, noting, however, that access to third-generation TKIs is limited in most developing countries and cost barriers are high.
Of note, the relatively low dose of PCI used in this study was not associated with significant differences in Mini-Mental State Examination or quality of life scores in the short-term. Long-term assessments are needed, he said, concluding that, while additional study is needed to confirm the findings, the results, including the overall survival benefit seen with PCI, “highlight the benefits of this approach, particularly among patients with a high risk of developing brain metastases.”
Invited discussant Nasser Hanna, MD, the Tom and Julie Wood Family Foundation Professor of Lung Cancer Clinical Research at Indiana University, Indianapolis, said the findings of this “interesting and important study,” are intriguing, but agreed that additional study is needed.
“The study is far too small ... to definitively make this conclusion [that PCI improves iPFS in this population]; I would not recommend PCI without confirmatory data from larger, randomized trials,” he said.
Dr. Arrieta reported advisory roles or provision of expert testimony for Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche, Merck, Takeda, and Bristol-Myers Squibb, and receipt of honoraria and/or research funding from AstraZeneca, Boehringer Ingelheim, Merck, Roche, and Bristol-Myers Squibb. Dr. Nasser reported receiving research grants from Bristol-Myers Squibb, AstraZeneca, Genentech, and Merck.
SOURCE: Arrieta O et al. WCLC 2018, Abstract MA08.02.