Sep 29

PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care

3532 - Efficacy and Safety of Induction Therapy in Patients with Unresectable Stage III Driver Gene-Positive Non-Small Cell Lung Cancer

03:45pm - 05:00pm ET

Poster Hall - Exhibit Hall A

Screen: 23

Presenter(s)

Yuhan Lin, MD - Department of Radiation Oncology and Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical, Jinan, Shandong

Y. Lin^1,2, J. Zhao², W. Wen², D. Chen³, X. Hu², and J. Yu³; ¹School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China, ²Cancer Hospital Of Shandong First Medical University, Jinan, Shandong, China, ³Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China

Purpose/Objective(s): Induction therapy for unresectable stage III non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements remains controversial. This study compares the efficacy and safety of various induction regimens, particularly in patients with bulky disease.

Materials/Methods: We retrospectively analyzed 97 patients with unresectable stage III driver gene–positive NSCLC who received definitive chemoradiotherapy at Shandong Cancer Hospital between 2020 and 2024. Patients were grouped by induction regimen: chemotherapy alone, tyrosine kinase inhibitor (TKI) monotherapy, chemotherapy plus TKI, or no induction. A prespecified subgroup analysis evaluated outcomes in patients with bulky disease, defined as a primary tumor diameter =5 cm or a metastatic lymph node short-axis diameter =2 cm. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) following induction therapy and definitive chemoradiotherapy, overall survival (OS), dosimetric parameters, and treatment-emergent adverse events (AEs). Survival was estimated using the Kaplan–Meier method and compared with the log-rank test. AEs were graded per CTCAE v5.0.

Results:

Of 97 patients, 64 received induction therapy: 29 with chemotherapy alone, 17 with TKI monotherapy, 18 with chemotherapy plus TKI, and 33 with no induction. Baseline characteristics—including age, sex, smoking status, EGFR mutation subtype, co-occurring genomic alterations, clinical stage, and concurrent chemoradiotherapy regimen—were balanced across groups. Induction therapy improved median PFS versus no induction (29 vs 16 months; p=0.026). Within the induction cohort, the chemotherapy–TKI combination prolonged PFS compared with chemotherapy alone (54 vs 16 months; HR=0.27, p<0.0001) and TKI monotherapy (54 vs 29 months; HR=0.26, p=0.002). In bulky disease, the combination group achieved notably longer PFS versus no induction (59 vs 9 months; HR=0.30, p=0.021). Median OS was also longer with combination versus TKI alone (70 vs 40 months; HR=0.35, p=0.018). Post-induction ORR was higher with combination than with chemotherapy (50% vs 14%; p<0.01) or TKI alone(50% vs 12%; p=0.01); Lung V5 and V20 were lower with TKI induction versus no induction (p=0.01 and p=0.032) and versus chemotherapy (p<0.01). Grade =2 radiation esophagitis, pneumonitis, and myelosuppression were less frequent in the combination and TKI groups than in the chemotherapy group.

Conclusion: For unresectable stage III EGFR-mutant NSCLC, induction therapy improves prognosis. The chemotherapy–TKI combination offers superior efficacy—prolonging PFS and OS and improving ORR—with pronounced benefit in bulky disease and a favorable safety profile.