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Table 3 A narrative synthesis of clinical and patient-centered outcomes

From: Efficacy of systemic oncological treatments in patients with advanced esophageal or gastric cancers at high risk of dying in the middle and short term: an overview of systematic reviews

SRs Author, year Reported outcomes
OS RCTs/ RCTs overview PFS RCTs/ RCTs overview FS Toxicity RCTs/ RCTs overviewa Symptom related to disease QoL RCTs/ RCTs overview Admissions QoD
Iacovelli 2014 [23] 5/5 NR NR NR NR NR NR NR
Veer 2016 [24] 8/8 2d-line ramucirumab and 2d- or 3d-line everolimus and regorafenib showed limited PFS gain, ranging from 0.3 to 1.6 months 5/8 Targeted agents, either in monotherapy or combined with CT showed increased toxicity compared to BSC and CT-alone 5/8 NR
Wang 2016 [25] 3/3 NR NR NR
Chan 2017 a [26] 4/4 the addition of AAs was associated with improved PFS: HR 0.68 (95% CI 0.63–07.4, p < 000001) 4/4 toxicity > = Grade 3: with OR 139 (95% CI 117–165) 2/4 significant improvement in QoL was found with apatinib, in improving insomnia (p = 0002), ramucirumab in delaying time to deterioration of PS > = 2 (p = 0002) and improving functional functioning and nausea (HR < 075), bevacizumab in slowing deterioration in pain (p = 00068), and endostatin in improving global QoL (p < 005) 2/4
Chan 2017 b [27] 4/5 TLT improved PFS (HR 0.29; 95% CI 0.18–0.45) 3/5 more toxicities occurred in the TLT arms 5/5 The QOL data could not be combined in a meta-analysis because only brief descriptions were reported in their final publications 4/5
Harvey 2017 [28] 4/5 NR NR NR
Janmaat 2017 [15] 5/5 people who receive more CT or targeted therapeutic agents live with less disease progression than people who receive BSC or less therapy 2/5 NR NR
Wagner 2017 [29] 3/3 NR Because of the different ways of reporting, grade I to IV toxicities can be compared only within, but not between studies. Overall, treatment-associated toxicities were higher in the combination of CT arms, but this was usually not statistically significant 3/3 NR
Wang 2017 [30] 2/2 NR 1/2 the addition of TAs to therapies significantly increased the risk of developing severe AEs (RR: 1.12, 95% CI: 1.02–1.24, P = 0.02), but not for FAEs (RR: 0.97, 95% CI: 0.65–1.45, P = 0.88) 2/2 NR
Xie 2017 [31] NR NR Compared with other analyzed treatments, ramucirumab has a higher risk of hematological events during its application. Lapatinib is always combined with severe gastrointestinal events. Trastuzumab is proposed for its high efficacy in improving the survival rate and safety, which is proper for most patients 2/2 NR
Zhu 2017 [32] 5/5 NR NR NR
Liu 2018 [33] 4/4 targeting VEGFR drugs significantly improved PFS [HR 0.50, 95% CI (0.34, 0.66), P < 0.001] 4/4 Fewer AESIs were observed in the VEGFR-Ab than the VEGFR-TKI drugs. VEGFR drugs were effective, and their toxicity is within a controllable range 4/4 NR
Zhao 2018 [34] 6/6 apatinib (97.5%) was most likely to improve PFS, followed by regorafenib (86.3%) and rilotumumab (65.4%). 6/6 bevacizumab (85.5%) was likely to get the lowest severe AEs, followed by sunitinib (63%) 5/6 NR
Chen 2019 [35] 2/2 NR 1/2 The most common grade ≥ 3 TRAEs were fatigue, aspartate aminotransferase increased, hepatitis, pneumonitis, colitis, hypopituitarism. The TRAE incidence of anti-PD-1/PD-L1 was less than chemotherapy (TRAE RR = 0.64 p < 0.001; ≥3 TRAE RR = 0.37 p < 0.001). The incidence of ≥3 TRAEs of anti-PD-1/PD-L1 treatment was less than that of anti-CTLA-4 (11.7% vs 43.9%) 2/2 NR
van Kleef 2019 [36] NR NR NR taxanes and targeted agents could provide HRQoL benefit beyond the first-line compared with BSC 8/8
Wallis 2019 [37] 1/4 NR NR NR
  1. AAs Anti-angiogenic agents, BSC best supportive care, AE Adverse events, CT chemotherapy, FAE Fatal adverse events, FS Functional status, OS Overall survival, PFS Progression-free survival, QoD Quality of death, QoL Quality of life, TA Targeted agents, TLT third-line treatment
  2. Outcomes in bold are primary outcomes
  3. OS has been presented in Fig. 4 (meta-analysis)
  4. a RCTs: randomized controlled trials relevant to our question / RCTs overview: total randomized controlled trials included in the SR