Sejung Park1, Chung Mo Nam2, Seul-Gi Kim3, Ji Eun Mun4, Sun Young Rha5, Hyun Cheol Chung6. 1. Department of Biostatistics and Computing, Yonsei University College of Medicine, Seoul, South Korea; Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: SEUPARK@yuhs.ac. 2. Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: CMNAM@yuhs.ac. 3. Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: SOPHIA311@yuhs.ac. 4. Department of Biostatistics and Computing, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: MUNJE622@yuhs.ac. 5. Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea; Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: RHA7655@yuhs.ac. 6. Songdang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea; Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: UNCHUNG8@yuhs.ac.
Abstract
BACKGROUND: The most effective agent for the third-line treatment of advanced/metastatic gastric cancer (AGC) has not yet been determined. The aim of this network meta-analysis is to compare the relative efficacy and tolerability of third-line treatments for AGC. MATERIALS AND METHODS: We conducted a comprehensive literature review of randomised clinical trials (RCTs) using four electronic databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) were used as efficacy or tolerability outcomes. A Bayesian network meta-analysis with a random-effects model was used. RESULTS: Seven RCTs involving 2601 patients and nine treatments were included. The results suggested that 1 mg/kg nivolumab (nivolumab1) + 3 mg/kg ipilimumab (ipilimumab3) (hazard ratio [HR] 0.59, 95% credible interval [Crl] 0.38-0.91) was the most effective treatment, followed by nivolumab (HR 0.63, 95% Crl 0.50-0.79), for prolonging OS. Regorafenib (HR 0.40, 95% Crl 0.28-0.58) was most likely to improve PFS, followed by apatinib (HR 0.45, 95% Crl 0.33-0.60). Nivolumab1 + ipilimumab3 and nivolumab were better at improving ORR, whereas nivolumab1 + ipilimumab3 had the highest toxicity based on the AEs. For benefit-risk ratio, nivolumab, apatinib or regorafenib appeared to be the best options. Chemotherapy or two different dose combinations of nivolumab and ipilimumab were ranked as the next options because of poor tolerability, despite good efficacy. CONCLUSION: Immunotherapy (nivolumab) or antiangiogenic agents (regorafenib and apatinib) are associated with benefits for benefit-risk ratio as third-line monotherapy. This study might serve as a guideline to aid in the selection of third-line treatments for AGC.
BACKGROUND: The most effective agent for the third-line treatment of advanced/metastatic gastric cancer (AGC) has not yet been determined. The aim of this network meta-analysis is to compare the relative efficacy and tolerability of third-line treatments for AGC. MATERIALS AND METHODS: We conducted a comprehensive literature review of randomised clinical trials (RCTs) using four electronic databases. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) were used as efficacy or tolerability outcomes. A Bayesian network meta-analysis with a random-effects model was used. RESULTS: Seven RCTs involving 2601 patients and nine treatments were included. The results suggested that 1 mg/kg nivolumab (nivolumab1) + 3 mg/kg ipilimumab (ipilimumab3) (hazard ratio [HR] 0.59, 95% credible interval [Crl] 0.38-0.91) was the most effective treatment, followed by nivolumab (HR 0.63, 95% Crl 0.50-0.79), for prolonging OS. Regorafenib (HR 0.40, 95% Crl 0.28-0.58) was most likely to improve PFS, followed by apatinib (HR 0.45, 95% Crl 0.33-0.60). Nivolumab1 + ipilimumab3 and nivolumab were better at improving ORR, whereas nivolumab1 + ipilimumab3 had the highest toxicity based on the AEs. For benefit-risk ratio, nivolumab, apatinib or regorafenib appeared to be the best options. Chemotherapy or two different dose combinations of nivolumab and ipilimumab were ranked as the next options because of poor tolerability, despite good efficacy. CONCLUSION: Immunotherapy (nivolumab) or antiangiogenic agents (regorafenib and apatinib) are associated with benefits for benefit-risk ratio as third-line monotherapy. This study might serve as a guideline to aid in the selection of third-line treatments for AGC.
Authors: Miao Huang; Jisheng Li; Xuejun Yu; Qian Xu; Xue Zhang; Xin Dai; Song Li; Lei Sheng; Kai Huang; Lian Liu Journal: Front Oncol Date: 2021-10-22 Impact factor: 6.244