The oncologist
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Neuroendocrine tumors (NETs) are a heterogeneous group of tumors, with >50% of cases involving the gastrointestinal system or pancreas. Somatostatin analogs (SSAs) are used for treating NET-related secretory syndromes and, more recently, for their antiproliferative effects. We conducted a systematic review of published literature on the antiproliferative efficacy and safety of the SSA lanreotide Autogel in the management of NETs to gain a fuller understanding of the evidence and identify future areas of research. ⋯ Current clinical evidence shows that lanreotide Autogel has good antiproliferative activity with favorable safety and tolerability in patients with GEP-NETs, suggesting it should be considered as an early first-line treatment in this population. Further studies are needed to assess the potential benefits of higher doses and the use of lanreotide Autogel in combination therapy and as maintenance therapy in the absence of disease progression following other therapies. The Oncologist 2017;22:272-285 IMPLICATIONS FOR PRACTICE: This review presents the current clinical evidence for the antiproliferative activity of lanreotide Autogel in patients with midgut or pancreatic neuroendocrine tumors (NETs) and shows its effectiveness, safety, and tolerability in these patient populations. By systematically presenting all the clinical evidence, the review adds to existing publications by discussing results in a broad range of settings. The review also indicates future directions for investigation of the use of lanreotide Autogel in NETs originating in other locations, in combination therapy, or as maintenance therapy in progressive disease.
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Randomized Controlled Trial
A Phase II Randomized Trial (GO27827) of First-Line FOLFOX Plus Bevacizumab with or Without the MET Inhibitor Onartuzumab in Patients with Metastatic Colorectal Cancer.
Dysregulated hepatocyte growth factor/mesenchymal-epithelial transition (MET) signaling is associated with poor prognosis and resistance to vascular endothelial growth factor inhibition in metastatic colorectal cancer (mCRC). We report outcomes from a double-blind, multicenter phase II trial of the MET inhibitor onartuzumab in combination with mFOLFOX-6 and bevacizumab for mCRC (GO27827; NCT01418222). ⋯ Onartuzumab combined with mFOLFOX-6 and bevacizumab did not significantly improve efficacy outcomes in either the ITT or MET IHC-positive populations. MET expression by IHC was not a predictive biomarker in this setting. The Oncologist 2017;22:264-271 IMPLICATIONS FOR PRACTICE: The addition of onartuzumab to mFOLFOX-6 plus bevacizumab did not improve outcomes in patients with previously untreated metastatic colorectal cancer in this randomized, phase II study. Although initial results with onartuzumab were promising, a number of phase II/III clinical trials have reported a lack of improvement in efficacy with onartuzumab combined with standard-of-care therapies in several tumor types. Furthermore, negative study data have been published for rilotumumab and ficlatuzumab, both of which block hepatocyte growth factor binding to the mesenchymal-epithelial transition (MET) receptor. MET immunohistochemistry was not a predictive biomarker. It remains to be seen if other biomarkers or small molecule inhibitors may be more appropriate for inhibiting this oncogenic pathway.
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Early palliative care for advanced cancer patients improves quality of life and survival, but less is known about its effect on intensive care unit (ICU) use at the end of life. This analysis assessed the effect of a comprehensive early palliative care program on ICU use and other outcomes among patients with advanced cancer. ⋯ Early palliative care significantly reduced ICU use at the end of life but did not change ICU events. This study supports early initiation of palliative care for advanced cancer patients before hospitalizations and intensive care. The Oncologist 2017;22:318-323 IMPLICATIONS FOR PRACTICE: Palliative care has shown clear benefit in quality of life and survival in advanced cancer patients, but less is known about its effect on intensive care. This retrospective cohort study at a university hospital showed that in the last 6 months of life, palliative care significantly reduced intensive care unit (ICU) and hospital admissions, reduced deaths in the hospital, and increased hospice enrollment. It did not, however, change patients' experiences within the ICU, such as number of procedures, code status, length of stay, or disposition. The findings further support that palliative care exerts its benefit before, rather than during, the ICU setting.
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Historically, lung cancer was long considered a poorly immunogenic malignancy. In recent years, however, immune checkpoint inhibitors have emerged as promising therapeutic agents in non-small cell lung cancer (NSCLC). To date, the best characterized and most therapeutically relevant immune checkpoints have been cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein-1 (PD-1) pathway. ⋯ Based on these encouraging results, multiple different PD-1/PD-L1 inhibitors have entered clinical development, and two agents (nivolumab and pembrolizumab) have gained regulatory approval in the United States for the treatment of NSCLC. In several large, randomized studies, PD-1/PD-L1 inhibitors have produced significant improvements in overall survival compared with single-agent docetaxel delivered in the second-line setting, effectively establishing a new standard of care in NSCLC. In the present report, we provide an overview of the rationale for checkpoint inhibitors in lung cancer, recent clinical trial data, and the need for predictive biomarkers.
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The present study assessed the impact of the retrieval of >25 lymph nodes (LNs) on the survival outcome of patients with advanced gastric cancer after curative-intent gastrectomy. ⋯ Retrieving more than 25 lymph nodes during curative-intent gastrectomy substantially improved survival and survival stratification of advanced gastric cancer without compromising patient safety. The Oncologist 2017;22:97-106Implications for Practice: D2 lymph node (LN) dissection is currently the standard of surgical management of gastric cancer, which is rarely audited by a third party. The present study, one of the largest surgical series worldwide, has shown that the traditionally recognized retrieval of ≥16 LNs during curative-intent gastrectomy might not be adequate in regions in which locally advanced gastric cancers predominate. The presented data show that retrieval of >25 LNs, which more greatly mimics D2 dissection, improves long-term outcomes and survival stratification without compromising patient safety.