Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer.

INTRODUCTION: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. MATERIALS AND METHODS: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments. RESULTS: Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively. CONCLUSIONS: ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.

An Extremely Rapid Case of Pneumonitis with the Use of Nivolumab for Pancreatic Adenocarcinoma.

Pancreatic cancer is the fourth most common cancer death in the United States despite comprising a small percentage of the total number of cancer cases. The estimated 5-year overall survival (OS) for patients with distant metastatic disease is approximately 3%. New treatment options are an unmet need and remain an area of active investigation. A 53-year-old male with metastatic pancreatic cancer presented to the hospital with acute-on-chronic respiratory failure approximately 24 hours after receiving a novel therapeutic combination. Chest imaging showed marked changes as concerning for pneumonitis. Infectious workup was negative. The patient had initial clinical improvement after receiving initial intravenous steroids and oxygen support but eventually deteriorated later opting for supportive measures only. With infection ruled out, drug-induced pneumonitis was felt to be the likely cause of the radiologic and clinical changes. The rapidity of onset of symptoms is the aspect being highlighted in this case.

A Rare Case of Glioblastoma Multiforme with Osseous Metastases.

Glioblastoma multiforme is the most common malignant primary central nervous system neoplasm in adults. It has a very aggressive natural history with a median overall survival estimated at 14.6 months despite multimodality treatment. Extracranial metastases are very rare with few case reports published to date. We report the case of a 65-year-old male who underwent maximal safe resection for a newly diagnosed brain mass after presentation with new neurologic symptoms. He then received standard postsurgical adjuvant treatment for glioblastoma. Subsequently, he underwent another resection for early progressive disease. Several months later, he was hospitalized for new-onset musculoskeletal complaints. Additional investigation revealed new metastatic osseous lesions which were initially felt to be a new malignancy. The patient opted for supportive care and died 12 days later. Despite choosing no treatment, he elected to undergo a bone biopsy to understand the new underlying process. Results were that of metastatic GBM and were reported after the patient expired. Physicians caring for patients with GBM and new nonneurologic symptoms may contemplate body imaging.