Assessing Patient Risk, Benefit, and Outcomes in Drug Development: Insights From Afatinib Clinical Trials Across Diverse Cancer Indications.

PURPOSE: In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk. METHODS: In this investigation, we screened literature databases and clinical trial registries for trials of afatinib as monotherapy or in combination interventions for cancer treatment. We extracted participant demographics, adverse event characteristics, as well as clinical and surrogate endpoints for each trial. Studies were deemed positive, negative, or indeterminate based on their achieving of primary endpoints as well as their safety. RESULTS: Our search yielded 2444 articles; we excluded 2352 articles for a final inclusion of 92 trials of 8859 patients. Our sample had 49 (53%) positive trials, 27 (29%) negative trials, and 16 (17%) indeterminate trials. The most common off-label indications for afatinib were breast cancer and squamous cell carcinoma of head and neck. The median OS for all trials was 8.4 months, median PFS 3.4 months, and the total ORR was 29.6%. Our study found that trials performed in disease states beyond the initial indications were largely negative with little patient benefit. The adverse events within our trial sample appear to be in line with expectations for toxicity. IMPLICATIONS: These results are consistent with other studies that present similar findings, such as in Carlisle et al which indicate limited efficacy in nonapproved indications. Future trials should keep this potential evidence and patient burden in mind before initiation of those trials. This study contributes to the understanding of afatinib's risk-benefit profile across many clinical applications.

Hyperbaric oxygen therapy treatment as an alternative for a chronic sinus tract after chordoma surgery and radiation.

Chordoma is a rare form of cancer that forms from the notochord remnants, and affects the skull and the spine. The standard treatment for a sacrococcygeal chordoma is surgery and radiation. Chordoma has a high rate of recurrence and surgery with radiation treatment can leave patients with surgical site complications, such as wounds, fistulas or sinus tracts. Repeat surgical intervention on an irradiated surgical site increases incidence of complications leading to decreased quality of life, and increased morbidity and mortality. Treatment of wound complications after surgery and high-dose radiation for a chordoma tumour is rarely reported in the literature. Herein, the author describes the case of a chronic sinus tract after surgery and radiation for a sacral chordoma tumour successfully healed by hyperbaric oxygen therapy (HBOT) in conjunction with topical antibiotics.