Main Session
Sep 28
PQA 02 - Lung Cancer/Thoracic Malignancies, Patient Reported Outcomes/QoL/Survivorship, Pediatric Cancer

2524 - Impact of Radiotherapy Timing on Survival and Progression-Free Outcomes in Stage III-IV Non-Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors: A Retrospective Analysis

04:45pm - 06:00pm PT
Hall F
Screen: 15
POSTER

Presenter(s)

Fatma Yilmaz, MD - UPMC, Pittsburgh, PA

F. B. Yilmaz1, S. Taekman2, Z. A. Yilmaz3, S. Ribeiro Papp1, and A. Atrash1; 1UPMC, Harrisburg, PA, 2Drexel University College of Medicine, Philadelphia, PA, 3Erciyes University, Faculty Of Medicine, Kayseri, Kayseri, Turkey

Purpose/Objective(s): The optimal timing of radiotherapy (RT) with immune checkpoint inhibitors (ICI) for non-small cell lung cancer (NSCLC) remains unclear. While concurrent ICI and RT may provide synergistic benefits, their impact on overall survival (OS), progression-free survival (PFS), and immune-related adverse events (irAEs) requires further study.

Materials/Methods: This retrospective cohort study utilized TriNetX to identify stage III-IV NSCLC patients who received PD-1/PD-L1 inhibitors (pembrolizumab, nivolumab, atezolizumab, durvalumab, cemiplimab). A total of 7,420 patients were analyzed in three groups:

  • ICI Alone (Control) (N=2,294)

  • ICI + Concurrent RT (RT within 1 month of ICI) (N=1,857)

  • ICI + Sequential RT (RT >1 month after ICI) (N=3,269)

Primary outcome: OS (Kaplan-Meier survival analysis). Secondary outcomes: PFS (proxy defined by time to next systemic therapy, hospice referral, or palliative care) and toxicity profiles (rates of pneumonitis, colitis, myocarditis, endocrinopathies, hepatitis). PSM was applied to balance age, sex, smoking history, and comorbidities.

Results:

  • ICI Alone vs. ICI + Concurrent RT:

    • Median OS: 487 vs. 450 days (p=0.043)

    • PFS: Higher in ICI alone (p<0.0001)

    • No significant difference in irAEs (p=0.619)

  • ICI Alone vs. ICI + Sequential RT:

    • Median OS: 499 vs. 402 days (p<0.0001)

    • PFS: Higher in ICI alone (p<0.0001)

    • No significant irAE difference (p=0.4312)

  • Concurrent vs. Sequential RT:

    • No OS difference (p=0.3404)

    • PFS: Improved with concurrent RT (p<0.01)

    • No significant irAE difference (p=0.4477)

Subgroup analyses showed no significant differences after PSM for tumor burden, histology, or prior therapy. PD-L1 expression, ECOG status, and prior therapy details were unavailable.

These findings contribute to ongoing clinical trials exploring RT sequencing in NSCLC and highlight the need for personalized treatment strategies. While RT timing did not significantly alter OS, concurrent RT was associated with better PFS than sequential RT. Similar toxicity rates across groups suggest RT timing does not increase irAE risks. However, the lack of PD-L1 expression data limits further stratification. Future studies incorporating PD-L1 status and ECOG performance may refine patient selection for RT sequencing.

Conclusion: ICI monotherapy was associated with better OS and PFS than combination therapy with RT. However, concurrent RT demonstrated improved PFS over sequential RT. No significant increase in irAEs was observed across groups. Further prospective trials are needed to evaluate the impact of RT timing in NSCLC patients receiving ICI.