Real-World Practice Patterns of Immunotherapy, Chemotherapy, and Targeted Therapy with Radiation Therapy in Early-Stage Node-Negative Non-Small Cell Lung Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 120; no. 2; pp. e52 - e53
• Main Authors: Oh, P., Sasse, A., Wells, N., Kim, S.Y., Goldberg, S.B., Park, H.S.M.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-10-2024
• ISSN: 0360-3016
• DOI: 10.1016/j.ijrobp.2024.07.1893

Large prospective studies have demonstrated the clinical benefit of chemotherapy and immunotherapy with radiotherapy (RT) in unresectable locally advanced non-small cell lung cancer (NSCLC) to improve disease-related outcomes including survival. The use of systemic therapy, including targeted therapy, has also been shown to improve outcomes in patients with resectable disease. However, the value of combining these systemic therapies with RT for early-stage node-negative disease is less well-defined. Our aim was to evaluate real-world trends in systemic therapy use with RT in this context.
The nationwide Flatiron Health, longitudinal, and de-identified electronic health record-derived database was utilized to conduct a real-world retrospective, observational study. Inclusion criteria were diagnosis of early-stage node-negative NSCLC (cT1-3N0M0) between 2019-2023 and treatment with definitive RT with or without first-line systemic therapy. Chi-square, Wilcoxon rank-sum, and multivariable regression analyses were used to identify variables associated with receipt of systemic therapy with RT. The Cochran-Armitage test was used to assess for trends in systemic therapy use over time.
Among 1,699 patients treated with RT, systemic therapy was administered to 260 patients (15%), including chemotherapy to 207 (10% neoadjuvant, 77% concurrent, 33% adjuvant) and immunotherapy to 105 (6% neoadjuvant, 9% concurrent, 95% adjuvant). Targeted therapy was given to 33 patients (5%). There were no statistically significant differences in age, sex, race, smoking status, insurance, or socioeconomic status associated with systemic therapy use. Higher T stage was significantly associated with systemic therapy on multivariable analysis (p<0.001). Among patients with T3N0 disease (n = 198), 24% received immunotherapy compared to 4% in those with T1-2N0 disease (p<0.001), while 51% received chemotherapy for T3N0 disease compared to 7% in those with T1-T2N0 disease (p<0.001). The use of immunotherapy was not significantly associated with PD-L1 status (7% for PD-L1 0% vs. 10% for PD-L1 1-49% vs. 10% for PD-L1≥50%, p = 0.3). Targeted therapy was used in 33% of patients with an EGFR mutation compared to 3% in wild-type patients. From 2019 to 2023, there was a trend towards increased use of any systemic therapy for T1-T2N0 (p = 0.022), but not T3N0 tumors.
Despite the lack of high-level evidence supporting the use of systemic therapy in patients with early-stage node-negative NSCLC treated with RT, modern real-world data suggests frequent off-label use of chemotherapy, immunotherapy, and targeted therapy especially in T3N0 tumors, but increasingly even for T1-T2N0 disease. Therefore, additional prospective data on the benefit of systemic therapy in early-stage node-negative NSCLC is warranted.