{
  "abstract": "Background The benefits of immune checkpoint inhibitors (ICIs) observed in clinical trials often fail to translate to patients with cancer treated in a real-world setting. Identifying modifiable exposures, such as baseline medication status, that may influence ICI efficacy is critical for reconciling disparities between clinical trial and real-world patient outcomes.Methods This multi-center cohort study was conducted across community oncology clinics participating in the RADIOHEAD study, a prospective, pan-tumor cohort of immunotherapy-naïve patients undergoing standard of care immune checkpoint inhibitor (ICI) treatment. Baseline medication data were obtained through electronic data capture for 1,024 patients. This number reflects the subset of the full cohort (N = 1,070) with complete information for survival and stage. Survival analyses were performed to evaluate associations between both individual and cumulative medication exposures and real-world overall survival (rwOS).Results Of 1024 patients from the RADIOHEAD cohort, 55% of patients (n = 564/1024) were exposed to polypharmacy, defined as more than 5 drug classes, at baseline. Polypharmacy, explored as at this threshold and as a continuous measure of cumulative medication exposure, was significantly associated with worse rwOS (HR 1.06, (95% CI 1.03-1.10), p<0.001, q=0.005). Among individual medication class exposures, there was a strong association between opioids and worse rwOS [HR 1.79 (95% CI 1.43-2.24), p<0.001], as well as beta-blocker use [HR 1.38, (95% CI 1.10-1.72), p = 0.005], after adjusting for clinically relevant covariates and patterns of co-prescription. The hazard associated with non-cardioselective beta-blockers [HR 1.60, (95% CI 1.15-2.24), p = 0.006] appeared greater than that of cardioselective medications [HR 1.32, (95% CI 1.04-1.68, p = 0.02]. The association between opioid exposure and worse rwOS was independent of other palliative care medications [HR 1.61, (95% 1.09-2.36 CI) p=0.016, P for interaction = 0.4] and persisted in patients with early-stage and non-metastatic disease.Conclusions This study demonstrates that baseline medication use holds prognostic relevance for rwOS in ICI-treated patients with cancer. To our knowledge, this is the first study to evaluate the influence of baseline medications while accounting for cumulative co-prescription exposures. While polypharmacy may adversely influence ICI efficacy, our findings suggest that specific medication classes, particularly baseline opioids and beta-blockers, may strongly contribute to this association. Importantly, these findings persist after adjusting for correlates of advanced disease, including cancer stage and metastatic burden. Notably, we present evidence that use of non-cardioselective beta-blockers, compared to cardioselective beta-blockers, may also pose a greater risk to ICI-treatment outcomes.",
  "authors": [
    {
      "affiliations": [
        "Huntsman Cancer Institute, Salt Lake City, UT, USA",
        "University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Samantha Stone"
    },
    {
      "affiliations": [
        "Huntsman Cancer Institute, Salt Lake City, UT, USA",
        "University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Muhammad Z Fadlullah Wilmot"
    },
    {
      "affiliations": [
        "University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Yuxin Zhao"
    },
    {
      "affiliations": [
        "Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA"
      ],
      "name": "Samantha I Liang"
    },
    {
      "affiliations": [
        "Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA"
      ],
      "name": "EnJun Yang"
    },
    {
      "affiliations": [
        "Huntsman Cancer Institute, Salt Lake City, UT, USA"
      ],
      "name": "Jordan McPherson"
    },
    {
      "affiliations": [
        "Huntsman Cancer Institute, Salt Lake City, UT, USA",
        "University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Aik Choon Tan"
    },
    {
      "affiliations": [
        "Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA"
      ],
      "name": "John E Connolly"
    },
    {
      "affiliations": [
        "UCSF, San Francisco, CA, USA"
      ],
      "name": "Zoe Quandt"
    },
    {
      "affiliations": [
        "University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Ben J Brintz"
    },
    {
      "affiliations": [
        "University of Utah, Salt Lake City, UT, USA",
        "University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Arabella Young"
    }
  ],
  "title": "477 Association of baseline medication exposure with real-world overall survival in patients with cancer treated with immune checkpoint inhibitors in the RADIOHEAD cohort",
  "uid": "07eed61a-c4e4-5270-b883-64e974fc9e93"
}