Yervoy’s FDA-approval was based upon a recent pivotal Phase III, double-blind international study that randomized 676 patients with unresectable or metastatic melanoma. Hodi et al. reported all patients in the study had stopped responding to other FDA-approved or commonly used treatments of melanoma, such as aldesleukin, dacarbazine, temozolomide, fotemustine, or carboplatin. The study excluded patients with active autoimmune disease or those receiving systemic immunosuppression for organ transplantation. According to the FDA, “The study was designed to measure overall survival, the length of time from when this treatment started until a patient's death. The randomly assigned patients received Yervoy alone, Yervoy plus an experimental tumor (peptide) vaccine called gp100, or the vaccine alone. Those who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of about 10-months, while those who received only the experimental vaccine lived an average of 6.5 months.” The assessment of the tumor response was conducted at week 12 and 24, and every three-months thereafter. The published study revealed the estimated overall survival at one-year was 46% in the Yervoy arm, 44% in the Yervoy and vaccine arm, and 25% in the vaccine alone arm. At two-years, the overall survival was 24% in the Yervoy arm, 22% in the Yervoy and vaccine arm, and 14% in the vaccine alone arm.
The FDA label comes with a label warning prompted by severe, life-threatening or fatal autoimmune-mediated adverse reactions (12.9% of patients treated with Yervoy) experienced during earlier phase II and III trials. When the severe reactions occurred, Yervoy was stopped and corticosteroid treatment was started. Due to the unusual and severe side effects associated with Yervoy, the therapy was approved with a Risk Evaluation and Mitigation Strategy informing health care professionals about these serious risks.
The National Comprehensive Cancer Network (NCCN) panel included Yervoy as a Category I recommendation for metastatic melanoma. Category I designation of the NCCN Categories of Evidence and Consensus is that the therapy recommendation is based upon high-level evidence; the consensus is that the intervention is appropriate.
Several unpublished trials have examined the use of Yervoy as monotherapy or in combination with chemotherapy or radiation therapy for the treatment of prostate cancer and non-small cell lung cancer. Improved health outcomes have not been demonstrated. The evidence is not sufficient to support the use of Yervoy beyond its FDA-approved indication.
Additional Information in 2012
A search of peer reviewed literature through March 2012 identified new clinical trial information regarding additional uses of Yervoy. According to the National Cancer Institute, there are multiple clinical trials targeting the use of Yervoy, with or without other pharmaceutical preparations, in prostatic cancer (phases I to III), breast cancer (no specified phase established), solid organ tumors (phase I), urothelial cancer (phase II), and non-small cell lung cancer (phases I to III) (Clinical Trials, 2012). According to the literature, Yervoy is also being investigated in a phase III trial for use in chronic myeloid leukemia (CML), non-Hodgkin’s lymphoma (NHL), and renal cell carcinoma. Study results have not been found in published peer reviewed literature (Drugs, 2011; Tarhini, 2010; Morse, 2005).