Chapter 9 204 ILLUSTRATION: EXPANDED ACCESS OF VEMURAFENIB FOR MELANOMA To illustrate our method in practice, we here jointly analyze data from the vemurafenib clinical trial and the vemurafenib expanded access program. Vemurafenib is a drug currently approved for the treatment of late-stage melanoma harboring a V600E BRAF mutation. The United States (US) Food and Drug Administration (FDA) approved vemurafenib in 2011 for patients who progressed on chemotherapy based in part on a single-arm phase II study (N = 132).41 The European Medicines Agency (EMA) approved vemurafenib in 2012. In addition to the regulatory studies, expanded access programs were set-up to grant patients unable to partake in the trials the opportunity to access vemurafenib prior to regulatory approval.42 At 29 sites across the US, 371 patients received vemurafenib while simultaneously generating data on the treatment patterns, safety, and efficacy of vemurafenib in a real-world setting. We obtained individual patient data from the trial and expanded access program through the data sharing platform Vivli. The data access request and analysis plan can be obtained online through Vivli.15 The inclusion criteria of the expanded access program were less stringent than the criteria of the clinical trial, recruiting a broader patient population compared with the trial. For example, patients could only be included in the trial if they had an Eastern Cooperative Oncology Group (ECOG) performance score - a measure of physical fitness - of 0 or 1, whereas in the expanded access program, 19% of the patients had a worse performance score of 2 or 3. Similarly, 75% of patients in the EAP had stage M1c disease, meaning the cancer had spread throughout the body, compared with only 61% of patients in the trial. Table 2 displays the differences in patient characteristics among a subset of (prognostic) variables across the trial and the expanded access program. For the expanded access program, 64% (241/371) of expanded access patients had efficacy assessments available and were included in the analysis. 15 https://vivli.org/combining-data-from-expanded-access-programs-and-conventional-clinical-trials-a-statisticalapplicationto-vemurafenib/
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