Evaluating Toxicity and Interaction Outcomes of Systemic Therapy and Stereotactic Ablative Radiotherapy for Oligometastatic Disease: A Secondary Analysis of the Phase II SABR-5 Trial

Purpose/Objective(s)

While SABR is known for its overall low toxicity and safety, there remains a research gap regarding its combined use with specific systemic therapies. This study aims to evaluate the toxicity of SABR in combination with various systemic therapies. The hypothesis is that certain systemic therapies would significantly increase the risk of Grade 2+ and Grade 3+ radiation therapy-related toxicities when used concurrently with Stereotactic Ablative Radiotherapy (SABR).

Materials/Methods

A secondary analysis of the SABR-5 trial compared grade 2+ and 3+ toxicities associated with SABR until the last follow-up in patients receiving high-risk or non-high-risk systemic therapy at intervals of 3 months, 2 weeks, 1 week, and concurrently with SABR. High-risk systemic therapy was a priori defined, based on previous literature, as drugs that, when given close to SABR, may increase treatment toxicity. This category encompasses cytotoxic chemotherapy drugs, multi-targeted tyrosine kinase inhibitors, cyclin-dependent kinase 4/6 inhibitors, epidermal growth factor receptor inhibitors, anti-vascular endothelial growth factor agents, and anti-cytotoxic T-lymphocyte-associated protein 4 agents.

Results

Among the 381 patients, the actuarial rates of grade 2+ and 3+ toxic effects were as follows: for patients not on systemic therapy 3 months prior to SABR (n = 202), the rates were 17.3% and 3.5%, respectively; for patients on non-high-risk systemic therapy concurrent with SABR (n = 102), the rates were 18.6% and 3.9%, respectively; and for patients on high-risk systemic therapy concurrent with SABR (n = 5), the rates were notably higher at 60% and 40%, respectively. On multivariable analysis, concurrent use of high-risk systemic therapy was associated with a higher risk of grade 2+ (OR = 7.15, P = 0.043) or 3+ toxic effects (OR = 13.9, P = 0.015). Significance was not observed when high-risk drugs were used only within 1 week, 2 weeks, or 3 months of SABR, nor with the use of any non-high-risk drugs. A second adverse factor included increased tumor diameter (per 1 cm increment; G2+ OR = 1.25, P < 0.001; G3+ OR = 1.27, P = 0.015).

Conclusion

High-risk drugs have demonstrated a potential of increased SABR-related toxicity, warranting caution in their concurrent use with SABR. In contrast, the combination of non-high-risk drugs with SABR may be safe. Ongoing efforts are essential to identify potential risks and uncertainties associated with this therapeutic combination.