Role of Immune Checkpoint Inhibitors in Small Cell Lung Cancer.

BACKGROUND: Small cell lung cancer (SCLC) accounts for approximately 13% of all lung cancer diagnoses each year. SCLC is characterized by a rapid doubling time, early metastatic spread, and an unfavorable prognosis overall. AREAS OF UNCERTAINTY: Most patients with SCLC will respond to initial treatment; however, the majority will experience a disease recurrence and response to second-line therapies is poor. Immune checkpoint inhibitors may be an option given the success in other diseases. DATA SOURCES: A literature search was conducted using Medline (1946-July week 1, 2017) and Embase (1996-2017 week 28) with the search terms small cell lung cancer combined with nivolumab or ipilimumab or pembrolizumab or atezolizumab or tremelimumab or durvalumab. Five clinical trials, including extended follow-up for 2, that evaluated immune checkpoint inhibitors in limited stage or extensive stage SCLC were included. RESULTS: In 2 phase 2 trials, ipilimumab was added to upfront chemotherapy. In both trials, an improvement in progression-free survival was seen. Toxicity, when combined with a platinum and etoposide, was significant. In a confirmatory phase 3 trial, ipilimumab did not prolong overall survival when added to first-line chemotherapy. Overall, response rates were similar between the placebo and ipilimumab groups. A phase 1/2 trial evaluated nivolumab alone or in combination with ipilimumab in recurrent SCLC. Results revealed that nivolumab monotherapy and the combination of nivolumab and ipilimumab were relatively safe and had antitumor activity. Pembrolizumab has been evaluated in a multicohort, phase 1b trial. Preliminary data showed a durable response in the second-line setting. CONCLUSION: Given the lack of overall survival data and significant toxicity associated with the combination of ipilimumab with first-line chemotherapy, this treatment is not a reasonable option at this time. Nivolumab alone or in combination with ipilimumab is a valid option for recurrent SCLC.

New and Emerging Antibiotics for Complicated Intra-Abdominal Infections.

The purpose of this review is to evaluate the efficacy and safety of ceftazidime/avibactam and ceftolozane/tazobactam in patients with complicated intra-abdominal infections (cIAI), and review eravacycline and other agents in the pipeline for management of cIAI. The increasing incidence of multidrug resistant strains of bacteria has led to the need for additional antibiotics with activity against these organisms. There are 2 newly approved antibiotics, ceftazidime/avibactam and ceftolazane/tazobactam for treatment of cIAI. Both agents have been shown to exert activity against resistant bacteria, including extended-spectrum beta-lactamase-producing organisms. Several other antibiotics are currently under investigation for this indication. Included in the pipeline of agents is a new tetracycline, an aminoglycoside, 2 new fluroquinolones, and 2 new beta-lactamase inhibitor combinations with carbapenems. Although the mechanisms for these new agents are not novel, promising data have shown their ability to overcome class resistance. The passing of the Generating Antibiotic Incentives Now Act has led to an increasing number of fast tracked antibiotic approvals. In addition to recent approval of ceftazidime/avibactam and ceftolazane/tazobactam, several other emerging antibiotics are under investigation which will aid in the management of resistant cIAI.

Single-agent, broad-spectrum fluoroquinolones for the outpatient treatment of low-risk febrile neutropenia.

OBJECTIVE: To evaluate the use of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of low-risk febrile neutropenia (FN). DATA SOURCES: MEDLINE via Ovid (1948 to May, week 3, 2011) and EMBASE (1980 to 2011, week 21) were searched using the terms febrile neutropenia, fluoroquinolone, quinolone derivative, levofloxacin, moxifloxacin, and neoplasm. References of selected articles, review articles, and treatment guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION: Trials evaluating the efficacy of oral, single-agent, broad-spectrum fluoroquinolones in the treatment of chemotherapy-induced FN were included if the majority of patients in the study had low-risk FN. Trials involving pediatric patients, non-Food and Drug Administration-approved fluoroquinolones, or monotherapy with ciprofloxacin or ofloxacin were excluded. Data extracted included study design, patient demographics, antiinfective regimens, and treatment outcomes. DATA SYNTHESIS: Four clinical trials were included. One trial compared levofloxacin with piperacillin/tazobactam with a success rate (afebrile at 72 hours) of 76.5% in the levofloxacin group compared with 88.3% in the piperacillin/tazobactam group. This trial was not limited to low-risk patients. The remaining 3 trials investigated moxifloxacin monotherapy in low-risk patients. Two of these were noncontrolled trials with success rates (afebrile at 5 days) of 91% and 95%. The final trial randomized patients to moxifloxacin or ceftriaxone and had success rates (hospital discharge at 48 hours) of 79.2% and 73.9%, respectively. In all 4 trials, treatment of FN with levofloxacin or moxifloxacin was deemed to be safe and effective. Although all studies had positive results, they were limited by small sample sizes and the absence of universal use of control comparisons. CONCLUSIONS: Use of oral, single-agent, broad-spectrum fluoroquinolones for outpatient treatment of FN in low-risk patients has shown promising results. At this time, this type of therapy should be limited to low-risk patients. Future clinical trials should include larger sample sizes and a comparison with existing first-line oral therapy-oral ciprofloxacin plus amoxicillin/clavulanate.