Real-world outcomes associated with afatinib use in patients with solid tumors harboring NRG1 gene fusions
Stephen V Liu1, Claas Frohn2, Lori Minasi3
1Georgetown University, Washington, DC 20007, USA.
Objectives:
Neuregulin-1 (NRG1) fusions may drive oncogenesis via constitutive activation of ErbB signaling. Hence, NRG1 fusion-driven tumors may be susceptible to ErbB-targeted therapy. Afatinib (irreversible pan-ErbB inhibitor) has demonstrated activity in individual patients with NRG1 fusion-positive solid tumors. This study collected real-world data on demographics, clinical characteristics, and clinical outcomes in this patient population.
Materials And Methods:
In this retrospective, multicenter, non-comparative cohort study, physicians in the US-based Cardinal Health Oncology Provider Extended Network collected data from medical records of patients with NRG1 fusion-positive solid tumors who received afatinib (afatinib cohort) or other systemic therapies (non-afatinib cohort) in any therapy line. Objectives included demographics, clinical characteristics, and outcomes (overall response rate [ORR], progression-free survival [PFS], and overall survival [OS]).
Results:
Patients (N = 110) with a variety of solid tumor types were included; 72 received afatinib, 38 other therapies. In the afatinib cohort, 70.8 % of patients received afatinib as second-line treatment and Eastern Cooperative Oncology Group performance status (ECOG PS) was 2-4 in 69.4 % at baseline. In the non-afatinib cohort, 94.7 % of patients received systemic therapy as first-line treatment and ECOG PS was 2-4 in 31.6 % at baseline. In the afatinib cohort, ORR was 37.5 % overall (43.8 % when received as first-line therapy); median PFS and OS were 5.5 and 7.2 months, respectively. In the non-afatinib cohort, ORR was 76.3 %; median PFS and OS were 12.9 and 22.6 months, respectively.
Conclusion:
This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.
Insights
Neuregulin-1 (NRG1) fusions can drive cancer by activating ErbB signaling. Afatinib, an ErbB inhibitor, showed activity in patients with NRG1 fusion-positive solid tumors, though outcomes varied between treatment groups in this real-world study.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Neuregulin-1 (NRG1) fusions are implicated in oncogenesis through constitutive ErbB signaling.
- NRG1 fusion-driven tumors may respond to ErbB-targeted therapies like afatinib.
- Afatinib, an irreversible pan-ErbB inhibitor, has shown promise in individual cases.
Purpose of the Study:
- To collect and analyze real-world data on patients with NRG1 fusion-positive solid tumors.
- To describe the demographics, clinical characteristics, and outcomes of patients treated with afatinib versus other systemic therapies.
- To evaluate the efficacy of afatinib in this patient population.
Main Methods:
- Retrospective, multicenter, non-comparative cohort study.
- Data collected from medical records of patients with NRG1 fusion-positive solid tumors.
- Outcomes assessed included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
Main Results:
- 110 patients included: 72 received afatinib, 38 received other therapies.
- Afatinib cohort: ORR 37.5%, median PFS 5.5 months, median OS 7.2 months.
- Non-afatinib cohort: ORR 76.3%, median PFS 12.9 months, median OS 22.6 months.
Conclusions:
- Real-world data show durable responses in patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies.
- Significant imbalances between treatment cohorts limit direct outcome comparisons.
- Further prospective and retrospective trials are necessary to confirm these findings.
More Related Videos
06:51Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
09:49Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
