medwireNews: Patients with metastatic non-small-cell lung cancer (NSCLC) may benefit from the combination of radiotherapy and pembrolizumab, suggests a pooled analysis of two randomized controlled trials.
The researchers say in The Lancet Respiratory Medicine that “adding radiotherapy to pembrolizumab significantly increases response rates to unirradiated lesions, leading to a significant progression-free survival [PFS] and overall survival benefit.”
They explain that the phase 2 PEMBRO-RT and phase 1/2 MDACC trials both pointed to “a potential benefit” of the combination, but “owing to the small sample size of each trial, differences in response rates and outcomes were not statistically significant.”
The team continues: “We therefore did a pooled analysis of findings from these two trials to better assess the clinical endpoints.”
The pooled population consisted of 148 patients who were randomly assigned to receive pembrolizumab 200 mg every 3 weeks either with or without radiotherapy at a dose of 24 Gy given in three fractions (in PEMBRO-RT) or 50 Gy in four fractions or 45 Gy in 15 fractions (in MDACC). Pembrolizumab was initiated within a week of the last radiotherapy dose in the PEMBRO-RT trial, whereas it was given concurrently with radiation in the MDACC study.
After a median follow-up of 33 months, the best abscopal response rate was significantly higher with the combination than pembrolizumab alone, at 41.7% versus 19.7%, giving an odds ratio (OR) of 2.96. And this was also the case for best abscopal disease control rate, at 65.3% and 43.4%, respectively, and a significant OR of 2.51.
The combination was also associated with significantly improved median progression-free survival (9.0 vs 4.4 months) and overall survival (19.2 vs 8.7 months) relative to pembrolizumab alone, with hazard ratios of 0.67 for both endpoints, report Dawei Chen (Shandong Cancer Hospital and Institute, China) and team.
Overall, Chen and colleagues note that “[n]o new concerns about safety arose from this analysis.”
Chen et al highlight the “striking” difference in abscopal response between the 24 Gy and 50 Gy schedules compared with the 45 Gy schedule, with rates of 47.2% and 56.2% versus 20.0%, respectively. But they note that the “pooled analysis was not suited to address the comparative efficacy of various radiotherapy schedules,” and say that further investigation is warranted.
And they stress: “Taken together, conclusions regarding the optimum dosing, timing or location of radiotherapy to induce an abscopal response cannot be drawn from this study. Our hypothesis-generating findings should be corroborated in a dedicated, large-volume, randomised trial.”
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