2466 - Off-Protocol Radiotherapy in Prospective Systemic Therapy Trials for Metastatic Non-Small Cell Lung Cancer
Presenter(s)
K. M. Ruicci1,2, G. J. Li1,2, A. Youssef3, A. Parmar1,4, A. Mutsaers5,6, D. A. Palma5,6, and A. V. Louie1,2; 1Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada, 2Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 3University of Toronto, Toronto, ON, Canada, 4Department of Medical Oncology, University of Toronto, Toronto, ON, Canada, 5Division of Radiation Oncology, Western University, London, ON, Canada, 6Division of Radiation Oncology, London Health Sciences Centre, London, ON, Canada
Purpose/Objective(s): Radiotherapy is a commonly used treatment modality in patients with metastatic non-small cell lung cancer (NSCLC), whether for palliation of symptoms or ablation of metastases, and there is increasing evidence that radiotherapy alters the natural history of metastatic NSCLC. Here we evaluate prospective systemic therapy trials for protocol specifications and documentation of radiation use in the peri-trial setting, in order to enhance the interpretation of trial findings.
Materials/Methods: Clinicaltrials.gov was queried from inception to October 2024 for completed, phase II-IV systemic therapy trials for metastatic NSCLC. Protocol availability was required to assess peri-trial radiation allowance and published manuscripts were reviewed for radiotherapy reporting. Trial information was summarized using descriptive statistics. Fisher’s exact test and logistic regression were used to assess the association between trial-related factors, radiation allowance and trial positivity.
Results: A total of 405 trials were screened and 79 completed studies enrolling 42,164 patients were included. Most studies were phase III (63.3%, n=50), randomized (83.5%, n=66), industry-sponsored (83.5%, n=66) and unmasked (70.9%, n=56). Progression-free survival was the most common endpoint (39.2%, n=31). PD-1/PD-L1, EGFR and VEGF were the most common drug targets (46.9%, 34.2% and 15.2% of studies respectively). Most studies (93.7%, n=74) allowed radiation before trial enrollment and required a pre-specified washout; this was most commonly 6 months for prior radical thoracic radiation (24.1%, n=19 studies), or 2 weeks for prior palliative radiation (35.4%, n=28 studies). During the study period, off-protocol radiation was prohibited in 8.9% (n=7) of studies and not addressed in 27.8% (n=22) of studies. Of those allowing radiation, 21.5% (n=17) required a drug washout around the time of radiation delivery; 12.7% (n=10) of studies required the drug(s) to be held during radiation, and 6.3% (n=5) of studies required a 1-week washout before and after radiation delivery. Few trials provided specifications regarding radiation site (8.9%, n=7), duration of radiotherapy (1.3%, n=1) or volume limits (1.3%, n=1). No studies permitting off-protocol radiation addressed allowable total dose, fractionation or organ at risk dose constraints. VEGF-targeted trials were significantly less likely to permit off-protocol radiation (p=0.02). Allowance of off-protocol radiation was not significantly associated with trial positivity (OR 0.23; 95% CI, 0.01-1.49; p=0.19). Pre-enrollment radiation was ultimately reported in 32.9% (n=26) of studies, while no study reported off-protocol radiation use.
Conclusion: Among prospective systemic therapy trials for NSCLC, peri-trial radiation details are inconsistently reported. Given overlapping toxicities and common use of radiotherapy in this setting, future trials would benefit from clear parameters regarding peri-trial radiotherapy use.