WCLC Sept 2021 | Nintedanib plus steroid taper in radiation pneumonitis

Radiation pneumonitis is a quite common toxicity after radiotherapy for thoracic malignancies. It can occur in around 20% of patients or so after radiation treatment. And about half of patients who experience radiation pneumonitis will go on to have subsequent acute pulmonary exacerbations. So that can involve cough, shortness of breath, or can even require supplemental oxygen. And in the long term, it can progress to permanent decline in pulmonary function as a result of fibrosis, that results in the late stage of the disease. So, the current standard of care for radiation pneumonitis is a long taper of steroids, but there’s really a lack of perspective studies to guide treatment for this disease.

So I’m reporting the results of a Phase II randomized placebo-controlled trial, where we tested the efficacy of nintedanib plus a prednisone taper compared to placebo plus a prednisone taper for the treatment of radiation pneumonitis. And nintedanib is a multiple tyrosine kinase inhibitor that’s approved for use in idiopathic pulmonary fibrosis and this shares some of the same signal transduction pathways and its pathophysiology with radiation pneumonitis, which is why we used it in this study. So patients were enrolled who had grade 2 or higher radiation pneumonitis, and they were treated with an eight-week taper of prednisone in combination with either nintedanib or placebo. The target enrollment for the study was 68 patients, but the trial was stopped early due to slow accrual. The final enrollment was 34 patients and 30 of them were analyzable for the primary endpoint, which was freedom from pulmonary exacerbations at one year.

So we found that 72% of patients in the nintedanib arm were free from exacerbation at one year compared to 40% in the placebo arm. However, this difference was not statistically significant, though there was a trend towards benefit from nintedanib with a P-value of 0.07. The most common side effect in the nintedanib arm was diarrhea, but there were no grade 4 or grade 5 side effects that were related to the drug.

So overall this trial did not reach significance for the primary endpoint, but it’s important to note that the majority of patients in the placebo arm did experience acute pulmonary exacerbations after their initial diagnosis of radiation pneumonitis despite receiving the standard of care treatment with a long taper of oral prednisone. So this, again, emphasizes the need to improve treatment outcomes for radiation pneumonitis and the trend that we saw towards significance in the nintedanib the arm likely warrants additional evaluation of this drug in the treatment of this disease too.