Radiation therapy plus osimertinib vs osimertinib alone in epidermal growth factor receptor mutated non-small cell lung cancer: A systematic review

Table 4 Grading of Recommendations Assessment, Development and Evaluation Evidence Quality Assessment

Outcome	Studies (design)	Participants	Effect estimate	Quality of evidence	Rationale for downgrading
Third-generation EGFR-TKIs vs first/second-generation
Progression-free survival	4 RCTs	1201	HR: 0.46 (0.38-0.56)	High	No serious limitations
CNS objective response rate	3 RCTs	644	OR: 4.2 (2.8-6.3)	High	No serious limitations
Overall survival	2 RCTs	913	HR: 0.80 (0.64-0.99)	Moderate	Wide confidence intervals
Combined EGFR-TKI + radiotherapy vs EGFR-TKI alone
Intracranial control	6 observational	1156	HR: 0.52 (0.38-0.71)	Low	Observational studies with inherent limitations and significant heterogeneity between studies (I² > 50%)
Overall survival	4 observational	892	HR: 0.68 (0.51-0.91)	Low	Observational studies with inherent limitations and wide confidence intervals
Stereotactic radiosurgery vs whole brain radiotherapy
Cognitive preservation	3 RCTs	925	OR: 5.8 (3.2-10.5)	Moderate	Mixed population studies with limited EGFR-mutant specific data
Local control	5 mixed studies	1689	OR: 1.8 (1.2-2.7)	Low	Observational studies with inherent limitations and significant heterogeneity between studies (I² > 50%)
Treatment sequencing
Upfront EGFR-TKI vs Combined	4 observational	567	Variable outcomes	Very low	Observational studies with inherent limitations, significant heterogeneity between studies (I² > 50%), and wide confidence intervals

RCTs: Randomized controlled trials; CNS: Central nervous system; HR: Hazard ratio; EGFR: Epidermal growth factor receptor; TKI: Tyrosine kinase inhibitor; OR: Odds ratio.