Abstract 192P
Background
Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. RP can cause substantial morbidity and often progresses to permanent fibrosis. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares many pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a standard prednisone taper compared to a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP.
Methods
In this phase II, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib 150mg twice daily for 12 weeks or placebo, in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations within one year. Secondary endpoints included total number of exacerbations and pulmonary function tests (PFTs). Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbation. The study was closed early due to slow accrual.
Results
Thirty-four patients were enrolled, three patients withdrew consent, and one was not treated. Of the evaluable 30 patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to control Arm B (placebo + prednisone taper). Freedom from exacerbation at one year was 72% (CI 54%-96%) in Arm A and 40% (CI 20%-82%) in Arm B (one-sided p=0.037). In Arm A there were 16 G2+ adverse events possibly or probably related to treatment compared to five in the placebo arm. There were two deaths during the study period in arm A due to cardiac failure and progressive respiratory failure, respectively. No baseline patient characteristics were associated with freedom from exacerbations, and there were no statistically significant changes in PFTs between treatment arms.
Conclusions
After the initial onset of G2+ RP, treatment with nintedanib plus prednisone taper improved freedom from pulmonary exacerbations at one year compared to placebo plus prednisone taper. These findings show promise for the use of nintedanib in the treatment of radiation pneumonitis.
Clinical trial identification
NCT02496585.
Legal entity responsible for the study
The authors.
Funding
Boehringer Ingelheim, National Cancer Insititute.
Disclosure
A. Rimner: Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Varian Medical Systems; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Consulting: Boehringer Ingelheim; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Other, Consulting: Merck; Financial Interests, Personal, Other, Consulting: Cybrexa; Financial Interests, Personal, Invited Speaker, Honorarium: ResearchToPractice; Financial Interests, Personal, Other, Travel Support: Philips/Elekta; Non-Financial Interests, Personal, Advisory Board: Merck; Non-Financial Interests, Personal, Leadership Role: ITMIG; Non-Financial Interests, Personal, Leadership Role: IMIG; Financial Interests, Personal, Leadership Role: ASTRO. N. Shaverdian: Financial Interests, Institutional, Research Grant: Novartis. M.G. Zauderer: Financial Interests, Institutional, Sponsor/Funding: University of Michigan; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Precog; Financial Interests, Institutional, Research Grant: Polaris; Financial Interests, Institutional, Research Grant: Sellas Life Sciences; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Curis; Financial Interests, Institutional, Research Grant: Atara; Financial Interests, Personal, Other, Consulting: Takeda; Financial Interests, Personal, Other, Consulting: GSK; Financial Interests, Personal, Other, Consulting: Aldeyra Therapeutics; Financial Interests, Personal, Other, Consulting: Novocure; Financial Interests, Personal, Other, Consulting: Ikena; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Invited Speaker: Research to Practice; Financial Interests, Personal, Invited Speaker: Medical Learning Institute; Financial Interests, Personal, Invited Speaker: OncLive; Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation. C.M. Rudin: Financial Interests, Personal, Other, Consulting: AbbVie; Financial Interests, Personal, Other, Consulting: Amgen; Financial Interests, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Other, Consulting: Epizyme; Financial Interests, Personal, Other, Consulting: Genentech/Roche; Financial Interests, Personal, Other, Consulting: Ipsen; Financial Interests, Personal, Other, Consulting: Jazz; Financial Interests, Personal, Other, Consulting: Lilly; Financial Interests, Personal, Other, Consulting: Syros; Non-Financial Interests, Personal, Advisory Board: Bridge Medicines; Non-Financial Interests, Personal, Advisory Board: Earli; Non-Financial Interests, Personal, Advisory Board: Harpoon Therapeutics; Financial Interests, Personal, Member of the Board of Directors: LUNGevity; Non-Financial Interests, Personal, Advisory Board: LUNGevity. R. Mak: Non-Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.