e15102 Background: For patients with metastatic cancer treated on an early-phase clinical trial, disease progression typically prompts discontinuation of study drug and initiation of an alternative systemic therapy and/or supportive care. Emerging data suggests local therapies may provide clinical benefit when disease spread is limited (oligometastatic), potentially due to eradication of emergent resistant subclones of disease. Evidence in patients treated on early-phase investigational trials is limited. In this study, we test the hypothesis that radiation to oligoprogressive lesions (≤ 5 sites) can prolong potential benefit from systemic therapy and allow patients to remain on trial longer. Methods: We retrospectively reviewed patients on early-phase oncology trials within the Early Drug Development Service at Memorial Sloan Kettering Cancer Center between October 2009 to November 2023. Imaging and radiation records were reviewed to categorize patients into those who received metastasis-directed radiation therapy (RT) to all sites of oligoprogressive disease versus those receiving palliative RT only to selected lesions with other progressing disease left untreated. Kaplan-Meier methods were used to estimate time on trial (time from RT start to protocol treatment discontinuation), and log-rank test compared duration between groups. Results: Of 139 patients who received radiation for extracranial metastatic disease, 43% (60 patients) underwent palliative RT with additional sites of progression left untreated, 56% (78 patients) underwent metastasis-directed RT to all sites of progressive disease, and 1 patient underwent RT on 2 separate trials. 6% of patients (8/139) were identified with grade 4/5 toxicity, none of which were related to RT. 3 events preceded RT delivery and others were due to untreated disease progression. Median time from start of RT to discontinuation of study treatment was 41 days (95% CI: 29-63, range 3-582) for patients undergoing palliative RT with additional sites of progression left untreated, and was significantly longer, 141 days (95% CI: 106-213, range 7-2164), for patients receiving metastasis-directed RT to all sites of progression (p < 0.0001). Conclusions: In a large, single-center, early-phase trial experience, patients treated with metastasis-directed radiation to all sites of oligoprogression experienced extended time on trial, which was significantly longer compared to palliative RT leaving progressing disease untreated, with some patients benefiting for additional years. No serious adverse events related to RT occurred. These retrospective findings warrant further validation, as patient selection factors could influence outcomes. Metastatic ablation for progressing disease is a potentially powerful tool to extend the benefit of systemic therapy, and should be considered in trial design, even in the setting of exploring novel agents.
Bhutani et al. (Thu,) studied this question.