Recruitment, outcomes, and toxicity trends in phase I oncology trials: Six-year experience in a large institution.

BACKGROUND: With the rapid influx of novel anti-cancer agents, phase I clinical trials in oncology are evolving. Historically, response rates on early phase trials have been modest with the clinical benefit and ethics of enrolment debated. However, there is a paucity of real-world data in this setting. AIM: To better understand the changing landscape of phase I oncology trials, we performed a retrospective review at our institution to examine patient and trial characteristics, screening outcomes, and treatment outcomes. METHODS AND RESULTS: We analyzed all consecutive adult patients with advanced solid organ malignancies who were screened across phase I trials from January 2013 to December 2018 at a single institution. During this period, 242 patients were assessed for 28 different trials. Median age was 64 years (range 30-89) with an equal sex distribution. Among 257 screening visits, the overall screen failure rate was 18%, resulting in 212 patients being enrolled onto a study. Twenty-six trials (93%) involved immunotherapeutic agents or molecular targeted agents either alone or in combination, with only two trials of cytotoxic agents (7%). Twenty-two (13.4%) of the 209 treated patients experienced a total of 33 grade 3 or higher treatment-related adverse events. There was one treatment-related death (0.5%). Of 190 response-evaluable patients, 7 (4%) had a complete response, 34 (18%) a partial response, and 59 (31%) experienced stable disease for a disease control rate of 53%. The median overall survival for our cohort was 8.0 (95% CI: 6.8-9.2) months. CONCLUSION: The profile of phase I trials at our institution are consistent with the changing early drug development landscape. Response rates and overall survival in our cohort are superior to historically reported rates and comparable to contemporaneous studies. Severe treatment-related toxicity was relatively uncommon, and treatment-related mortality was rare.