Immunotherapy or Targeted Therapy Versus Best Supportive Care for Advanced Gastric Cancer: A Systematic Review and Meta-analysis of Randomized Trials
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Abstract
Purpose: To assess the efficacy and safety of non-chemotherapy anticancer drugs (immunotherapy or targeted therapy) compared to best supportive care (BSC) or placebo for the treatment of advanced gastric cancer (GC). Methods: Systematic review of randomized controlled trials (RCTs) searching (May 2022) MEDLINE, EMBASE, CENTRAL, Epistemonikos, ClinicalTrials.gov, and PROSPERO. Certainty of evidence was evaluated following GRADE. Results: Six RCTs included. Targeted therapies likely result in a slight increase in overall survival (OS) (HR 0.84, 95% CI 0.75, 0.93; moderate certainty) and progression-free survival (PFS) (HR 0.52, 95% CI 0.43, 0.62; moderate certainty). Toxicity had a slightly increased risk (RR 1.19, 95% CI 0.95, 1.48; low certainty). Immunotherapy also showed a likely improvement in PFS (HR 0.60, 95% CI 0.49, 0.73; moderate certainty), while toxicity showed a likely higher risk (RR 2.72, 95% CI 1.24, 5.94; moderate certainty). However, benefits in survival translated to time gains of slightly over a month for OS and less than a month for PFS. No data were reported on performance status (PS), hospital admissions, or quality of life (QoL). Conclusions: Our study suggests some survival benefits with low toxicity from these treatments, but gains are marginal. Uncertainties persist regarding their impact on QoL and outcomes for patients with poor PS. Caution is advised in treatment selection for advanced GC patients, who should actively participate in decision-making. Future research should include diverse patient populations and assess patient-centered outcomes with consistent comparator groups for BSC. Trial Registration: The study protocol was registered in OSF ( https://doi.org/10.17605/OSF.IO/7CHX6 ) on 2022–04-01.
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Cites
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21660 · Cited by 108,699 · see citing works
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · BMJ · doi:10.1136/bmj.n71 · Cited by 108,283 · see citing works
The Cochrane Collaboration's tool for assessing risk of bias in randomised trials
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., Sterne, J. A. C., et al. (2011) · BMJ · doi:10.1136/bmj.d5928 · Cited by 33,817 · see citing works
Rayyan-a web and mobile app for systematic reviews.
Ouzzani, M., Hammady, H., Fedorowicz, Z., & Elmagarmid, A. (2016) · Systematic Reviews · doi:10.1186/s13643-016-0384-4 · Cited by 26,092 · cited 1× · see citing works
“For all this process, we used the Rayyan platform [36].”
Dermyshi, E., Wang, Y., Yan, C., Hong, W., Qiu, G., Gong, X., & Zhang, T. (2017) · Neonatology · doi:10.1159/000454668 · Cited by 24,577 · see citing works
GRADE: an emerging consensus on rating quality of evidence and strength of recommendations
Guyatt, G. H., Oxman, A. D., Vist, G. E., Kunz, R., Falck-Ytter, Y., Alonso-Coello, P., & Schünemann, H. J. (2008) · BMJ · doi:10.1136/bmj.39489.470347.ad · Cited by 23,305 · see citing works
Cochrane Handbook for Systematic Reviews of Interventions
(2019) · doi:10.1002/9781119536604 · Cited by 14,828 · see citing works
Wohlin, C. (2014) · Proceedings of the 18th International Conference on Evaluation and Assessment in Software Engineering · doi:10.1145/2601248.2601268 · Cited by 4,234 · cited 2× · see citing works
“Furthermore, we manually reviewed the reference lists of relevant studies to identify any additional relevant articles [35].”
Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential
Sharma, P., & Allison, J. P. (2015) · Cell · doi:10.1016/j.cell.2015.03.030 · Cited by 2,345 · see citing works
Kang, Y., Boku, N., Satoh, T., Ryu, M., Chao, Y., Kato, K., Chung, H. C., Chen, J., Muro, K., Kang, W. K., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31827-5 · Cited by 2,254 · see citing works
Wilke, H., Muro, K., Cutsem, E. V., Oh, S., Bodoky, G., Shimada, Y., Hironaka, S., Sugimoto, N., Lipatov, O., Kim, T.-Y., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70420-6 · Cited by 2,200 · see citing works
Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · Revista Española de Cardiología · doi:10.1016/j.recesp.2021.06.016 · Cited by 2,095 · see citing works
Fuchs, C., Tomášek, J., Cho, J., Dumitru, F., Passalacqua, R., Goswami, C., Safran, H., dos Santos, L. D., Aprile, G., Ferry, D., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61719-5 · Cited by 2,031 · see citing works
Li, H., Yang, Y., Hong, W., Huang, M., Wu, M., & Zhao, X. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0089-y · Cited by 1,771 · see citing works
Industry sponsorship and research outcome
Lundh, A., Lexchin, J., Mintzes, B., Schroll, J. B., & Bero, L. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.mr000033.pub3 · Cited by 1,697 · see citing works
Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Smyth, E. C., Verheij, M., Allum, W., Cunningham, D., Cervantes, A. M. R., & Arnold, D. (2016) · Annals of Oncology · doi:10.1093/annonc/mdw350 · Cited by 1,560 · see citing works
Thrift, A. P., & El‐Serag, H. B. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2019.07.045 · Cited by 1,508 · see citing works
Declaración PRISMA 2020: una guía actualizada para la publicación de revisiones sistemáticas
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · Revista Española de Cardiología (English Edition) · doi:10.1016/j.rec.2021.07.010 · Cited by 1,313 · see citing works
Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Okines, A. F. C., Verheij, M., Allum, W., Cunningham, D., & Cervantes, A. M. R. (2010) · Annals of Oncology · doi:10.1093/annonc/mdq164 · Cited by 1,300 · see citing works
Li, J., Qin, S., Xu, J., Xiong, J., Wu, C., Bai, Y., Liu, W., Tong, J., Liu, Y., Xu, R., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.63.5995 · Cited by 975 · see citing works
Ohtsu, A., Ajani, J. A., Bai, Y.-X., Bang, Y., Chung, H. C., Pan, H.-M., Sahmoud, T., Shen, L., Yeh, K., Chìn, K., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.48.3552 · Cited by 484 · see citing works
Korean Practice Guideline for Gastric Cancer 2018: an Evidence-based, Multi-disciplinary Approach
Guideline Committee of the Korean Gastric Cancer Association (KGCA), D. W. G. &. R. P. (2019) · Journal of the Korean Gastric Cancer Association · doi:10.5230/jgc.2019.19.e8 · Cited by 393 · see citing works
The Influence of Industry Sponsorship on the Research Agenda: A Scoping Review
Fabbri, A., Lai, A., Grundy, Q., & Bero, L. A. (2018) · American Journal of Public Health · doi:10.2105/ajph.2018.304677 · Cited by 317 · see citing works
Pavlakis, N., Sjoquist, K. M., Martin, A. J., Tsobanis, E., Yip, S., Kang, Y., Bang, Y., Alcindor, T., O'Callaghan, C. J., Burnell, M. J., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.65.1901 · Cited by 233 · see citing works
Current status of immune checkpoint inhibitors for gastric cancer
Kono, K., Nakajima, S., & Mimura, K. (2020) · Gastric Cancer · doi:10.1007/s10120-020-01090-4 · Cited by 220 · see citing works
Kumar, P., Casarett, D., Corcoran, A., Desai, K., Li, Q., Chen, J., Langer, C., & Mao, J. J. (2012) · Journal of Palliative Medicine · doi:10.1089/jpm.2011.0217 · Cited by 141 · cited 1× · see citing works
“Moreover, these therapies may entail toxicities and adverse events (AEs) that substantially impact patients’ quality of life (QoL) and functional status [17, 18].”
Industry Funding of Clinical Trials: Benefit or Bias?
Chopra, S. S. (2003) · JAMA · doi:10.1001/jama.290.1.113 · Cited by 127 · see citing works
Chen, Z.-D., Zhang, P., Xi, H., Wei, B., Chen, L., & Tang, Y. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.744839 · Cited by 120 · see citing works
Lou, L., Wang, L., Zhang, Y., Chen, G., Lin, L., Jin, X., Huang, Y., & Chen, J. (2020) · BMJ Open · doi:10.1136/bmjopen-2019-033323 · Cited by 111 · see citing works
Consensus-based standards for best supportive care in clinical trials in advanced cancer
Zafar, S. Y., Currow, D. C., Cherny, N. I., Strasser, F., Fowler, R., & Abernethy, A. P. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70215-7 · Cited by 86 · see citing works
Liu, J.-Y., Peng, C., Yang, X., Huang, C., & Li, Y. (2018) · PubMed Central · Cited by 85 · see citing works
Kitchenham, B. A., Pearl Brereton, A., Turner, M., & Charters, S. (2006) · Cited by 83 · see citing works
Magnuson, A. M., Bruinooge, S. S., Singh, H., Wilner, K. D., Jalal, S. I., Lichtman, S. M., Kluetz, P. G., Lyman, G. H., Klepin, H. D., Fleury, M. E., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3868 · Cited by 82 · see citing works
Rizzo, A., Mollica, V., Ricci, A. D., Maggio, I., Massucci, M., Llimpe, F. L. R., Fabio, F. D., & Ardizzoni, A. (2019) · Future Oncology · doi:10.2217/fon-2019-0429 · Cited by 76 · see citing works
Kang, Y., Kang, W., Bartolomeo, M. D., Chau, I., Yoon, H. H., Cascinu, S., Ryu, M., Kim, J. G., Lee, K.-W., Oh, S. C., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz394.034 · Cited by 65 · see citing works
Chan, W., Yuen, K.-K., Siu, S. W.-K., Lam, K. O., & Kwong, D. L. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.05.002 · Cited by 44 · see citing works
Recent Advances in Systemic Treatments for HER-2 Positive Advanced Gastric Cancer
Kahraman, S., & Yalçın, Ş. (2021) · OncoTargets and Therapy · doi:10.2147/ott.s315252 · Cited by 35 · see citing works
Prognosis factors of advanced gastric cancer according to sex and age
Alshehri, A., Alanezi, H., & Kim, B. S. (2020) · World Journal of Clinical Cases · doi:10.12998/wjcc.v8.i9.1608 · Cited by 35 · see citing works
Best supportive care in clinical trials: review of the inconsistency in control arm design
Nipp, R. D., Currow, D. C., Cherny, N. I., Strasser, F., Abernethy, A. P., & Zafar, S. Y. (2015) · British Journal of Cancer · doi:10.1038/bjc.2015.192 · Cited by 34 · see citing works
Salazar, J., Bracchiglione, J., Salas-Gama, K., Antequera, A., Auladell-Rispau, A., Dorantes-Romandía, R., Meade, A.-G., Quintana, M. J., Requeijo, C., Rodríguez-Grijalva, G., et al. (2021) · European Journal of Cancer · doi:10.1016/j.ejca.2021.05.034 · Cited by 28 · see citing works
Self-citationSiebenhüner, A. R., Dosso, S. D., Helbling, D., Astaras, C., Szturz, P., Moosmann, P., Pederiva, S., Winder, T. L., von Burg, P., & Borner, M. (2021) · Oncology Research and Treatment · doi:10.1159/000518107 · Cited by 28 · see citing works
Santero, M., Bracchiglione, J., Acosta‐Dighero, R., Meade, A.-G., Antequera, A., Auladell-Rispau, A., Quintana, M. J., Requeijo, C., Rodríguez-Grijalva, G., Salas-Gama, K., et al. (2021) · BMC Cancer · doi:10.1186/s12885-021-08330-5 · Cited by 25 · see citing works
Self-citationRequeijo, C., Bracchiglione, J., Meza, N., Acosta‐Dighero, R., Salazar, J., Santero, M., Meade, A.-G., Quintana, M. J., Rodríguez-Grijalva, G., Selva, A., et al. (2023) · Clinical Epidemiology · doi:10.2147/clep.s431498 · Cited by 24 · see citing works
Self-citationPark, S., Nam, C. M., Kim, S., Mun, J. E., Rha, S. Y., & Chung, H. C. (2020) · European Journal of Cancer · doi:10.1016/j.ejca.2020.10.030 · Cited by 23 · see citing works
Santero, M., Meade, A.-G., Acosta‐Dighero, R., González, L., Melendi, S., Solà, I., Urrútia, G., Quintana, M. J., & Bonfill, X. (2022) · Clinical & Translational Oncology · doi:10.1007/s12094-022-02807-w · Cited by 22 · see citing works
Self-citationMo, L., Urbauer, D. L., Bruera, E. D., & Hui, D. (2021) · Supportive Care in Cancer · doi:10.1007/s00520-021-06245-2 · Cited by 21 · see citing works
Pan, Y.-T., Si, H., Deng, G., Chen, S., Zhang, N., Zhou, Q., Wang, Z.-K., & Dai, G. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.798415 · Cited by 21 · see citing works
Shen, J., & Wang, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.934249 · Cited by 18 · see citing works
Rubiales, Á. S., Sánchez-Gutiérrez, M. E., Flores, L. A., & Rivero, M. L. D. V. (2020) · Current Oncology · doi:10.3747/co.27.5365 · Cited by 16 · see citing works
Hess, L. M., Smith, D. M., Cui, Z. L., Montejano, L. B., Liepa, A. M., Schelman, W. R., & Bowman, L. (2020) · Journal of Drug Assessment · doi:10.1080/21556660.2020.1851504 · Cited by 16 · see citing works
Bracchiglione, J., Santero, M., Salazar, J., Requeijo, C., Grijalva, G. R., Savall-Esteve, O., Meza, N., Salas-Gama, K., Selva, A., Meade, A.-G., et al. (2020) · doi:10.17605/osf.io/7chx6 · Cited by 13 · see citing works
Self-citationSalazar, J., Bracchiglione, J., Acosta‐Dighero, R., Meza, N., Meade, A.-G., Quintana, M. J., Requeijo, C., Rodríguez-Grijalva, G., Santero, M., Selva, A., et al. (2023) · Supportive Care in Cancer · doi:10.1007/s00520-022-07564-8 · Cited by 12 · see citing works
Self-citationCheng, J., Cai, M., Shuai, X., Gao, J., Wang, G., & Tao, K. (2019) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2019.08.001 · Cited by 11 · see citing works
Macauley, R. C. (2018) · Oxford University Press eBooks · doi:10.1093/med/9780199313945.001.0001 · Cited by 11 · see citing works
Impact of race on dose selection of molecular-targeted agents in early-phase oncology trials
Yokota, T., Bendell, J. C., LoRusso, P. M., Tsushima, T., Desai, V., Kenmotsu, H., Watanabe, J., Ono, A., Murugesan, B. G., Silva, J., et al. (2018) · British Journal of Cancer · doi:10.1038/s41416-018-0102-1 · Cited by 10 · see citing works
Treatment with anticancer drugs for advanced pancreatic cancer: a systematic review
Salazar, J., Bracchiglione, J., Savall-Esteve, O., Antequera, A., Bottaro, D., Gutiérrez‐Valencia, M., Martínez-Peralta, S., Pericay, C., Tibau, A., Bonfill, X., et al. (2023) · BMC Cancer · doi:10.1186/s12885-023-11207-4 · Cited by 9 · see citing works
Self-citationNo Time to Waste: An Appraisal of Value at the End of Life
Quinn, K. L., Krahn, M. D., Stukel, T. A., Grossman, Y., Goldman, R., Cram, P. M., Detsky, A. S., & Bell, C. M. (2022) · Value in Health · doi:10.1016/j.jval.2022.05.004 · Cited by 8 · see citing works
Santero, M., de Mas, J., Rifà, B., Clavero, I., Rexach, I., & Bonfill, X. (2023) · Clinical & Translational Oncology · doi:10.1007/s12094-023-03219-0 · Cited by 8 · see citing works
Self-citationBracchiglione, J., Rodríguez-Grijalva, G., Requeijo, C., Santero, M., Salazar, J., Salas-Gama, K., Meade, A.-G., Antequera, A., Auladell-Rispau, A., Quintana, M. J., et al. (2023) · Cancers · doi:10.3390/cancers15030766 · Cited by 6 · see citing works
Self-citationSantero, M., Meade, A.-G., Selva, A., Roberto, A., Nicolas, M., Quintana, M. J., Bracchiglione, J., Requeijo, C., Josefina, S., Rodríguez-Grijalva, G., et al. (2023) · Journal of Evidence-Based Medicine · doi:10.1111/jebm.12539 · Cited by 6 · see citing works
Self-citationNCCN Guidelines® Updates: Gastric Cancer
(2022) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2022.202glup · Cited by 6 · see citing works
Kang, Y., Boku, N., Kang, W. K., Yoon, H. H., Cascinu, S., Al‐Batran, S., Houston, S., Park, C. H., McGinn, A. N., & Chau, I. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2017.35.15_suppl.tps4138 · Cited by 4 · see citing works
Santero, M., Requeijo, C., Quintana, M. J., Rodríguez, D., Bottaro, D., Macías, I., Pericay, C., Farina, N., Blanco, J. M., Urreta, I., et al. (2024) · Clinical & Translational Oncology · doi:10.1007/s12094-024-03436-1 · Cited by 3 · see citing works
Self-citation
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Niu, L., Nie, Y., & Liu, Q. (2025) · Cancer Management and Research · doi:10.2147/cmar.s543448 · Cited by 2 · see citing works
- Authors
- Meade, A., Santero, M., Savall-Esteve, O., Bracchiglione, J., Leache, L., Selva, A., Macias, I., Cerdà, P., & Bonfill Cosp, X.
- Affiliations
- Iberoamerican Cochrane Centre (ES)
- Universitat Autònoma de Barcelona (ES)
- Hospital de Sant Pau (ES)
- Navarre Institute of Health Research (ES)
- Corresponding author
- Santero, Marilina
- Venue
- Journal of Gastrointestinal Cancer
- Published
- 2025-03-04
- Volume
- 56
- Issue
- 1
- Pages
- 75-75
- ISSN
- 1941-6628 (ISSN-L)
- 1941-6636
- PMC
- PMC11876278
- OpenAlex
- W4408106083
- Cited by
- 1
- References
- 63
- Citations by year
- 2025: 1
- FWCI
- 0.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Gastrointestinal Cancer (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by)
- Funders
- Instituto de Salud Carlos III (PI18/00034, FI19/00335)
- Universitat Autònoma de Barcelona
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Surgery › Intraperitoneal and Appendiceal Malignancies
- Keywords
- advanced gastric cancer, immunotherapy, targeted therapy, best supportive care, overall survival, progression-free survival, treatment toxicity, quality of life, performance status, patient-centered decision-making
- MeSH terms
- Progression-Free Survival, Humans, Immunotherapy, Quality of Life, Stomach Neoplasms, Randomized Controlled Trials as Topic, Molecular Targeted Therapy
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