Combination of pembrolizumab and pelareorep promotes anti-tumour immunity in advanced pancreatic adenocarcinoma (PDAC).

BACKGROUND: We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915). METHODS: PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood. RESULTS: Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8+ T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4+ Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1+ cells touching CD8+ T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR. CONCLUSION: Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation.

Real-World Treatment Patterns and Clinical Outcomes in Advanced Gastrointestinal Neuroendocrine Tumors (GI NET): A Multicenter Retrospective Chart Review Study.

BACKGROUND: We assessed treatment patterns and outcomes of patients with advanced gastrointestinal (GI) neuroendocrine tumors (NET) at four large tertiary referral centers in the U.S. PATIENTS AND METHODS: We performed a retrospective chart review of patients aged ≥18 years at advanced GI NET diagnosis, treated between July 2011 and December 2014. Index date was the histologically confirmed diagnosis date of locally advanced/metastatic GI NET. Data included baseline characteristics, treatment patterns, progression, death, and GI NET-related health care resource utilization from index date through last contact or death. Time-to-event analyses, including treatment discontinuation, progression, and overall survival (OS), were performed using Kaplan-Meier analysis. RESULTS: We identified 273 patients; 156 (57%) had primary ileum NET, and 174 (64%) had functional NET. First-line treatments included somatostatin analog (SSA) alone (89%) or in combination (2%), liver-directed therapy (LDT; 8%), and cytotoxic chemotherapy or interferon (2%). One hundred fifty-five patients continued with second-line therapy, including SSA alone (17%) or in combination (75%, with 3% combined with peptide receptor radionuclide therapy), LDT (4%), and other treatments (3%). Median time (months) to first-line discontinuation was 154.0 for SSAs and 3.8 for cytotoxic chemotherapy. Overall median time to investigator-assessed progression following treatment initiation was 30.3 months. Median OS (months) following first-line initiation was 151.8 for all patients and 178.9 for first-line SSA. CONCLUSION: Our study illustrates the common use of SSAs in both first-line and subsequent treatment of patients with GI NETs, as well as the relatively long survival durations and multiple additional treatments received by patients with this condition. Treatment pattern assessment at later times, following approval of newer treatments, is warranted. IMPLICATIONS FOR PRACTICE: This study, assessing treatment patterns over a period of up to 30 years, showed that SSAs, LDT, cytotoxic chemotherapy, and interferon are common treatments for advanced GI NETs. SSAs alone or in combination with other treatments were the most frequent therapy in first and subsequent lines. Patients in this study remained on SSAs long-term, with median treatment duration of 12.8 years in first line. Treatment patterns should be assessed beyond this study's time period, given recent U.S. Food and Drug Administration approvals for additional treatments for GI NET, which will likely be incorporated in the continuum of care of patients.

Treatment Patterns and Clinical Outcomes in Advanced Lung Neuroendocrine Tumors in Real-World Settings: A Multicenter Retrospective Chart Review Study.

BACKGROUND: Using data from four tertiary referral centers in the U.S., we assessed real-world treatment patterns and clinical outcomes of patients with advanced lung neuroendocrine tumors (NETs). SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective chart review of adult patients with locally advanced/metastatic (typical/atypical) lung NETs treated between July 2011 and December 2014. Index date was histologically confirmed typical/atypical carcinoid tumor diagnosis date. Data included baseline characteristics, treatment patterns, progression, death, and lung NET-related health care resource use from index date through last contact/death. Time to treatment discontinuation and first progression, time from first to second progression, and overall survival (OS) were estimated using Kaplan-Meier analysis. RESULTS: We identified 83 patients; 19 (23%) had functional NET. First-line treatments included somatostatin analogs (SSAs) alone (56%) or in combination with other therapies (6%), cytotoxic chemotherapy (20%), external beam radiation therapy (EBRT) (9%), liver-directed therapy (LDT) (4%), and everolimus/other (5%). Sixty patients had second-line therapy including SSA alone (18%) or in combination (40%), cytotoxic chemotherapy (17%), everolimus (12%), LDT (7%), EBRT (3%), and other treatments (3%). Median time (months) to first-line discontinuation were as follows: SSAs, 43.3; cytotoxic chemotherapy, 3.6. Overall median time (months) to investigator-assessed progression following treatment initiation was 12.4. Median OS (months) following treatment initiation was 66.4 for all patients and 81.5 for patients receiving SSAs. CONCLUSION: SSAs, alone and in combination, are common treatments for advanced lung NETs. Patients have additional treatment options and relatively long survival compared with patients with other advanced cancers. Treatment pattern assessment following approval of newer treatments is needed. IMPLICATIONS FOR PRACTICE: Somatostatin analogs (SSAs), cytotoxic chemotherapy, EBRT, liver-directed therapy, and targeted therapies are common treatments for locally advanced/metastatic (typical/atypical) lung neuroendocrine tumors (NETs). SSAs alone or in combination with other treatment modalities were the most common first- and second-line therapy, followed by cytotoxic chemotherapy. Patients continued treatment with SSAs long-term with median treatment duration of 43 months. Median overall survival was 66 months following initiation of first-line therapy for all patients. Treatment pattern assessment beyond the time period of this study is needed given recent U.S. Food and Drug Administration approvals for additional treatments for lung NETs that will likely be incorporated in the treatment landscape.

NCCN Guidelines Insights: Antiemesis, Version 2.2017.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Antiemesis address all aspects of management for chemotherapy-induced nausea and vomiting. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Antiemesis, specifically those regarding carboplatin, granisetron, and olanzapine.