Concurrent palliative radiation with pembrolizumab for platinum-refractory urothelial carcinoma is associated with improved overall survival

Highlights

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  We investigated the hypothesis that palliative radiation to patients treated with pembrolizumab exerts a favorable effect on survival in 235 platinum-refractory metastatic urothelial carcinoma patients.

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  Overall survival from the initiation of pembrolizumab was significantly longer in patients who underwent concurrent palliative radiation with pembrolizumab than in both patients with palliative radiation before pembrolizumab and those without palliative radiation throughout the follow-up.

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  The result using propensity score matching still exhibited a longer overall survival in patients treated with concurrent palliative radiation with pembrolizumab than those without concurrent palliative radiation.

Abstract

Background and Purpose

Pembrolizumab has now become a standard of care in metastatic urothelial carcinoma (mUC), although the treatment effect of the drug substantially differs among individuals. Emerging evidence suggests that radiotherapy exerts a synergistic effect with PD-1 blockade. We sought to elucidate the survival outcomes in patients who underwent palliative radiation with the pembrolizumab treatment.

Methods

We retrospectively investigated our multi-institutional dataset of 235 platinum-refractory mUC patients treated with pembrolizumab as second-line treatment, collected from January 2018 and October 2021. Propensity score matching was performed to reduce biases by potential confounding factors for overall survival (OS).

Results

With a median follow-up of 6.8 months, the median OS from the initiation of pembrolizumab was 13 months in 235 patients. Palliative radiation was performed in 71 (30.2%) patients for whom the median radiation dose and fraction were 30 Gy and 10 fractions, respectively. Irradiated sites were bone in 24 (33.8%), lymph node in 17 (23.9%), lung in 3 (4.2%), brain in 8 (11.3%), and other sites in 19 (26.8%). OS from the initiation of pembrolizumab was significantly longer in patients who underwent concurrent palliative radiation with pembrolizumab (39 patients: median OS: 21 months) than in both patients with palliative radiation before pembrolizumab (32 patients: median OS: 9 months) (p = 0.001) and those without palliative radiation throughout the follow-up (164 patients: median OS: 13 months) (p = 0.019). After the propensity-score matching by putative confounding factors, longer OS in patients treated with concurrent palliative radiation with pembrolizumab (n = 36) was still observed compared to patients without the concurrent palliative radiation (n = 36) in the pair matched cohort (median OS of 29 and 13 months, respectively, p = 0.033).

Conclusions

Our findings suggest that the concurrent administration of palliative radiation with pembrolizumab offers a favorable effect on OS in platinum-refractory mUC patients.