155 A META-ANALYSIS OF EFFICACY AND SAFETY OF ANTI-BODIES TARGETING PD-1 IN TREATMENT OF ADVANCED ESOPHAGEAL CANCER

Systemic chemotherapy is the first choice for patients with advanced esophageal cancer. However, due to drug resistance and dose-limiting toxicity, a large number of patients in China have not been treated. A novel therapy based on programed death 1 (PD-1) inhibitors has been proved to be effective in advanced esophageal cancer.This article is a meta-analysis aiming to systematically evaluate the efficacy and safety of anti-PD-1 therapy in patients with esophageal cancer. Methods Data were collected from eligible studies searched from PubMed, Web of Science, Cochrane Library and Embase. Pooled hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) was estimated to assess the efficacy of PD-1 inhibitors versus chemotherapy, and pooled odds ratio (OR) was calculated for objective response rate (ORR). The analysis among patients tested with different PD-1 status was also performed to figure out the relationship between PD-1 status and efficacy of anti-PD-1 therapy. The OR for occurrence of treatment-related adverse effect was calculated to assess the safety of anti-PD-1 therapy. Results A total of 8 studies were analyzed. Compared with patients with chemotherapy, patients with anti-PD-1 therapy had a significant improvement in OS (HR = 0.80, 95% CI: 0.70–0.91, P = 0.001), but no significant relationship was observed in ORR (HR = 1.87, 95% CI: 0.82–4.25, P = 0.13) and PFS (HR = 0.94, 95% CI: 0.70–1.26, P = 0.67). A similar result was observed in esophageal squamous cell carcinoma (ESCC). The PD-L1 status has no obvious connection with the efficacy of anti-PD-1 therapy. The incidence of grade 3 to 5 treatment-related adverse effect(AE) in anti-PD-1therapy was distinctly lower than that in chemotherapy, but there is no statistical difference in all treatment-related AE. Conclusion Anti-PD-1 therapy significantly prolonged the OS when compared with chemotherapy, while no significantly difference in PFS and ORR for the population of esophageal cancer, ESCC， PD-L1 positive. Based on the analysis of grade 3 to 5 treatment-related adverse effect events, a lower risk was associated with the anti-PD-1 therapy versus chemotherapy.

Associations of Cutaneous Immune-Related Adverse Effects of Immunotherapy With Treatment Response in Patients With Metastatic Melanoma

Background: Dermatologic toxicity is the most common immune-related adverse effect of cancer immunotherapy. Methods: We retrospectively reviewed the health records of adult (≥18 years) melanoma patients who received ipilimumab, nivolumab, or pembrolizumab from January 1, 2011, through September 15, 2017, at Mayo Clinic. The χ2 test was used to assess the association between development of a cutaneous immune-related adverse effect and antitumoral response to the immune checkpoint inhibitors. Odds ratios were calculated with logistic regression models and were adjusted for sex and immunotherapeutic drugs. We described the various cutaneous immune-related adverse effects and assessed the response to immunotherapy (each patient’s objective clinical response was categorized as favorable [complete or partial response] or unfavorable). We then determined whether development of a cutaneous immune-related adverse effect was associated with the clinical response. Results: Of 690 melanoma patients, 232 (33.6%) had a cutaneous immune-related adverse effect. The most common effects were dermatitis (21.4%), pruritus (5.5%), and vitiligo (4.2%). Median (range) time to onset of dermatitis was 3 (0-7) weeks; lichenoid dermatitis, 12 (6-18) weeks; and vitiligo, 40 (12-96) weeks. Development of a cutaneous immune-related adverse effect was significantly associated with favorable clinical response. Conclusions: Development of cutaneous immune-related adverse effects is associated with favorable responses to nivolumab, ipilimumab, pembrolizumab, and ipilimumab plus nivolumab therapy in patients with metastatic melanoma.

The Efficacy and Safety of Anti-bodies Targeting PD-1 for Treatment in Advanced Esophageal Cancer: A Systematic Review and Meta-analysis

Background: A novel therapy based on programed death 1 (PD-1) inhibitors has been proved to be effective in advanced esophageal cancer. This article is a meta-analysis aiming to compare the efficacy and safety of anti-PD-1 therapy with chemotherapy in esophageal cancer.Patients and methods: Data were collected from eligible studies searched from PubMed, Web of Science, Cochrane Library and Embase. Pooled hazard ratio (HR) for overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) was estimated to assess the efficacy of PD-1 inhibitors versus chemotherapy. The subgroup analysis were also performed to evaluate the OS benefits. The OR for occurrence of treatment-related adverse effect was calculated to assess the safety of anti-PD-1 therapy.Results: A total of 4 studies were analyzed. Compared with patients with chemotherapy, patients with anti-PD-1 therapy had a significant improvement in OS (HR=0.79, 95% CI: 0.71-0.88, P<0.001), but no significant relationship was observed in PFS (HR=0.96, 95% CI: 0.76-1.20, P=0.69) and ORR (OR=1.92, 95% CI: 0.98-3.72, P=0.06). A similar result was observed in esophageal squamous cell carcinoma (ESCC). The significant predictor for treatment benefit with combination therapy versus chemotherapy alone were histology (P=0.009). The incidence of grade 3 to 5 treatment-related adverse effect in anti-PD-1 therapy was distinctly lower than that in chemotherapy, but there is no statistical difference in all treatment-related adverse effect.Conclusion: Anti-PD-1 therapy significantly prolonged the OS, simultaneously lowered grade 3 to 5 treatment-related adverse effect versus chemotherapy.

Characterizing the impact of magnesium and potassium-supplemented hydration with cisplatin and the subsequent electrolyte replacement requirements

Background Cisplatin-associated electrolyte dysregulation is a prevalent therapy-related adverse effect. There are numerous electrolyte-supplemented hydration regimens that have been evaluated, however these studies focused on the development of nephrotoxicity. The objective of this study was to characterize the impact of magnesium and potassium-supplemented hydration during cisplatin administration on subsequent magnesium and potassium imbalances. Methods A single-region retrospective study from central Texas at Baylor Scott & White Cancer Clinics who were treated with two or more cycles of cisplatin were included. Standard hydration for this study was defined as normal saline before and after cisplatin along with potassium chloride 10 mEq and magnesium sulfate 1 g added to the cisplatin bag. Results A total of 477 patients were included in the study with376 patients receiving the standard hydration. Overall, 17 percent of patients experienced a potassium level below 3.5 mEq/L, but no major depletion was observed. Thirty-three percent of the patients experienced a magnesium level below 1.8 mg/dL, and time to first rescue magnesium supplementation was 4 weeks. Conclusion Our study demonstrated despite routine magnesium and potassium supplementation in hydration, magnesium imbalances were observed. Potassium levels post cisplatin administration were maintained with minimal routine supplementation in hydration.

Lambert-Eaton Myasthenic Syndrome Secondary to Nivolumab and Ipilimumab in a Patient with Small-Cell Lung Cancer

We present a case of a 59-year-old male with a confirmed diagnosis of small-cell lung cancer (SCLC). He had progressive disease even after four cycles of cisplatin and etoposide chemotherapy and 21 cycles of radiation. He was therefore started on immunotherapy with nivolumab every 2 weeks and ipilimumab every 6 weeks. After 4 months of starting immunotherapy, he reported extreme fatigue, muscular weakness, and poor appetite. He was diagnosed with hypothyroidism, primary adrenal insufficiency, and Lambert-Eaton Myasthenic Syndrome (LEMS). LEMS can be both a paraneoplastic syndrome of SCLC and an adverse effect of immunotherapy. Currently, there is no diagnostic test available to determine if a case of LEMS is a paraneoplastic syndrome or immunotherapy-related adverse effect. In our patient, we felt that LEMS was an immunotherapy-related adverse effect rather being a paraneoplastic syndrome. Our determination was based on the time of onset of muscular weakness, presence of other immunotherapy-mediated adverse events, and the appearance of symptoms in spite of SCLC that had been stabilized on immunotherapy. Accordingly, immunotherapy was stopped and a brief tapering course of steroids was initiated. Our patient’s muscular weakness from LEMS responded well. His clinical improvement persisted even with radiologic progression of disease after cessation of immunotherapy.