Trends in Oral Abstracts Presented at ASTRO from 2011-2019: Radiation-Drug Combinations.

Abstract

PURPOSE/OBJECTIVE(S)\nDespite the promise of improving the therapeutic ratio of radiation with novel pharmaceuticals, the last drug to receive FDA approval for use in combination with radiation was over 15 years ago. We sought to examine the oral abstracts presented at the ASTRO annual meetings over the past 9 years that involved drugs or biologics used concurrently with radiation, with the goal of reporting trends and identifying opportunities to accelerate drug development in this area.\n\n\nMATERIALS/METHODS\nAll published abstracts selected for an oral scientific session at the ASTRO annual meeting from years 2011-2019 were manually reviewed. Abstracts pertaining to drug-radiotherapy combinations aimed at improving anti-tumor efficacy or minimizing radiation toxicities were included in our analysis and categorized by type of study (preclinical, retrospective, phase 1, 2, or 3), disease site, category of drug (radiosensitizer, radioprotector, supportive care), specific drug class (immunotherapy, cytotoxic, etc.), and FDA approval status of drug/biologic at time of presentation. Descriptive statistics were used to identify trends over time.\n\n\nRESULTS\nA total of 3,089 abstracts were reviewed and 258 (8.4%) met our pre-specified criteria for a study investigating drug-radiotherapy combinations. The relative number of abstracts discussing radiation-drug combinations ranged from 6.2% (2015) to 10.9% (2011) of the total number of abstracts selected for oral presentation. Of the prospective trials presented, 25% were phase 1, 51.5% phase 2, and 23.5% phase 3. The most common drug class studied in clinical trials was cytotoxic chemotherapy. Of the investigational agents explored in phase 3 trials (N\u202f=\u202f39), all but 2 had previously received marketing approval for use in other indications. The only exceptions to this were avasopasem manganese (a novel radioprotector), and an unspecified oral mucosa protectant that may or may not require marketing approval prior to use. None of the clinical data presented has been used as primary efficacy data to support an FDA indication. Expected trends were observed, such as the use of anti-angiogenic and anti-EGFR agents decreasing over time and the use of immune modulatory agents increasing over time.\n\n\nCONCLUSION\nDespite an explosion of targeted therapies in oncology, the majority of clinical trials of drug-radiotherapy combinations presented at ASTRO Annual Meetings investigated cytotoxic chemotherapeutics that had already received marketing approval. The pharmaceuticals investigated in phase 3 trials during this time period had been FDA approved for a median of 25 years at the time of oral presentation and none of the data has been used to support FDA approval. This suggests a lack of support from Industry and Cooperative Groups for late phase combination trials with novel agents as well as a lack of incentives for Sponsors to seek supplemental indications with radiation.