Background Induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) has been recommended as the first-line therapy for locoregional nasopharyngeal carcinoma (NPC). Due to the different chemotherapeutic drugs used in the IC and CCRT, the results remain controversial. Methods PubMed, EMBASE, Web of Science, and Cochrane Library databases were systematically retrieved to search potentially eligible clinical trials up to Sep 11, 2019. Eligible studies were registered and prospective randomized controlled clinical trials. Results From 526 records, nine articles including seven randomized controlled clinical trials were eligible, with a total of 2311 locoregional advanced NPC patients. IC + CCRT had significantly lower risks of death (3-year hazard ratio [HR]: 0.70, 95% confidence interval [CI] 0.55–0.89, p = 0.003; 5-year HR: 0.77, 95% CI 0.62–0.94, p = 0.01), disease progression (3-year HR: 0.67, 95% CI 0.55–0.80, p < 0.001; 5-year HR: 0.70, 95% CI 0.58–0.83, p < 0.0001), distant metastasis (3-year HR: 0.58, 95% CI 0.45–0.74, p < 0.0001; 5-year HR: 0.69, 95% CI 0.55–0.87, p = 0.001) and locoregional relapse (3-year HR: 0.69, 95% CI 0.50–0.95, p = 0.02; 5-year HR: 0.66, 95% CI 0.51–0.86, p = 0.002) than CCRT. Compared with CCRT, IC + CCRT showed higher relative risks of grade 3 or more neutropenia, thrombocytopenia, nausea, vomiting and hepatotoxicity throughout the course of treatment, and higher relative risks of grade ≥ 3 thrombocytopenia and vomiting during CCRT. Conclusion IC combined with CCRT significantly improved the survival in locoregional advanced NPC patients. Moreover, toxicities were well tolerated during IC and CCRT. Further clinical trials are warranted to confirm the optimal induction chemotherapeutic regimen in the future.

Background. The prognosis of patients with extensive-stage small cell lung cancer (SCLC) is poor. Adding an immune checkpoint inhibitor (ICI) to chemotherapy may exert a synergistic effect and improve survival outcomes. However, for treatment-naive extensive-stage SCLC patients, the efficacy of immunotherapy in combination with cytotoxic chemotherapy remains controversial. Objective. To evaluate the benefits and risks of the combination of immunotherapy and chemotherapy and to assess the comparative effectiveness of different first-line treatment strategies for extensive-stage SCLC. Methods. PubMed, Web of Science, EMBASE, and Cochrane Library were searched for randomized clinical trials studying different immunotherapeutics for patients with previously untreated extensive-stage SCLC up to Feb 16, 2020. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were objective response rate (ORR), disease control rate (DCR), and adverse events. Results. We identified 141 published records, and 4 studies (comprising 2202 patients) were included in the analysis. Immunotherapy (including ipilimumab, atezolizumab, and durvalumab) plus chemotherapy was associated with better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.93; risk ratio (RR) 0.90, 95% CI 0.81–1.00) and PFS (HR: 0.81, 95% CI 0.74–0.88; RR 0.96, 95% CI 0.93–0.99) than placebo plus chemotherapy. The addition of immunotherapy to chemotherapy showed similar improvement in ORR, DCR, and adverse events versus placebo plus chemotherapy. On the surface under the cumulative ranking (SUCRA) analysis, the anti-PD-L1 agent, atezolizumab, had the highest likelihood of achieving improved OS (93.4%) and PFS (95.0%). Conclusion. In the first-line setting, combining immunotherapy with chemotherapy is better than standard chemotherapy in terms of OS and PFS. Across the eligible studies, PD-L1 inhibitors might be preferred. Further explorations of more ICIs in the first-line treatment for extensive-stage SCLC patients should be needed.

Background: Gemcitabine combined the oral fluoropyrimidine capecitabine (GemCap) is an active antitumor therapy in the treatment of advanced or metastatic pancreatic cancer, and has been shown potential synergistic activity in previous clinical trials. In this study, we sought to systematically review and synthesize the efficacy and safety of GemCap in the treatment of advanced or metastatic pancreatic cancer.Methods: A systematic review was performed through PubMed, Cochrane Library, EMBASE, and Web of Science databases up to Jul 10, 2019 to identify clinical trials that included advanced or metastatic pancreatic cancer patients treated with GemCap. Data of overall survival (OS), progression-free survival (PFS), 1-year survival rate, objective response rate (ORR), disease control rate (DCR) and adverse events were extracted and meta-analyzed.Results: Fifteen studies were identified for systematic review, of which 13 were included in the metaanalysis. In comparison with Gem monotherapy, the pooled hazard ratios (HR) of GemCap treatment for OS and PFS were 0.85 (95%

BackgroundDoxorubicin/Adriamycin (ADM) alone or combined with ifosfamide (IFO) (AI) is available for previously untreated advanced soft tissue sarcoma (ASTS). However, the clinical choice between them remains controversial. In this pooled analysis, we comprehensively compared the efficacy and tolerability of AI versus ADM in patients with ASTS.MethodsPubMed, Web of Science, EMBASE, and Cochrane Library were systematically searched from inception to April 14, 2021. Eligible studies were randomized clinical trials comparing AI to ADM. The primary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Discontinuation rate (DR) and toxic death (TD) were explored as secondary outcomes.ResultsOverall, three open-label randomized phase 2/3 clinical trials with a total of 1108 newly diagnosed ASTS patients were enrolled. Between AI and ADM, pooled hazard ratios were 0.93 (95% confidence interval 0.58-1.50, p = 0.78) for OS and 0.85 (0.57-1.25, p = 0.41) for PFS. While pooled risk ratios for ORR, DR, and TD were 1.37 (0.94-1.99, p = 0.10), 1.04 (0.74-1.46, p = 0.82), and 0.68 (0.19-2.36, p = 0.54) respectively. No publication bias was observed across the studies.ConclusionIn the first-line setting, adding IFO to ADM failed to benefit ASTS patients against ADM alone, even with comparable tolerability.

Background Immune checkpoint inhibition has been increasingly used in breast cancer therapy. Understanding the benefit and risk of programmed cell death 1 ( PD-1 ) and programmed cell death ligand 1 ( PD-L1 ) inhibitors is critical for clinical practice. This study aims to determine the objective response, disease control and adverse events of breast cancer patients treated with PD-1 / PD-L1 inhibitors. Methods PubMed, Cochrane Library, Web of Science and EMBASE databases were searched up to Aug 1, 2019. Both nonrandomized and randomized studies were included. Pooled objective response rate (ORR), disease control rate (DCR) and adverse events were pooled analyzed. Results A total of nine clinical studies were identified. Triple-negative breast cancer (TNBC) showed the highest estimates of ORR [overall population: 49.7%, 95% confidence interval (CI): 33.9–65.5%; PD-L1 positive population: 55.8%, 95% CI: 42.9–68.8%] and DCR (overall population: 67.5%, 95% CI: 38.6–96.4%; PD-L1 positive population: 83.4%, 95% CI: 72.2–94.5%) post-anti- PD-L1 plus nab-paclitaxel treatment. With respect to grade ≥3 treatment related adverse events, the pooled estimates ranged from 12.0% to 50.9% for anti- PD-1 / PD-L1 monotherapy. The pooled estimates percentages of grade ≥3 treatment related adverse events in TNBC patients treated with anti- PD-L1 plus nab-paclitaxel were 59.6% (95% CI: 36.1–83.0). Conclusions We presented the aggregate estimates of ORR, DCR, and treatment related adverse events for breast cancer patients receiving anti- PD-1 / PD-L1 treatment. However, these results were largely derived from single-arm studies, and randomized studies with head-to-head comparison of PD-1 / PD-L1 inhibitors and chemotherapy are lacking. Additionally, the incidence of varying treatment related adverse events should be also carefully monitored.