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Review
. 2023 Mar 17;9(2):FSO842.
doi: 10.2144/fsoa-2023-0002. eCollection 2023 Feb.

Recent advances in immunotherapy and molecular targeted therapy for gastric cancer

Yuri Yoshinami  1 , Hirokazu Shoji  1
Affiliations
Review

Recent advances in immunotherapy and molecular targeted therapy for gastric cancer

Yuri Yoshinami et al. Future Sci OA. .

Abstract

Our increasing understanding of the molecular biological characteristics of cancer and of cancer genomics is facilitating the development of immunotherapy and molecular targeted drugs for gastric cancer. After the approval of immune checkpoint inhibitors (ICIs) for melanoma in 2010, many different cancers have been shown to respond to such treatments. Thus, the anti-PD-1 antibody nivolumab was reported to prolong survival in 2017, and ICIs have become the mainstay of treatment development. Many clinical trials of combination therapies with cytotoxic agents and molecular-targeted agents, as well as combinations of immunotherapeutic agents acting via different mechanisms, are currently underway for each treatment line. As a result, further improvements in therapeutic outcomes for gastric cancer are anticipated in the near future.

Keywords: anti-PD-1 or PD-L1 inhibitors; gastric cancer; immune checkpoint inhibitors; immunotherapy; molecular targeted therapy.

Plain language summary

Gastric cancer is the fourth most common malignant tumor and also ranks fourth as a cause of death from cancer. However, even with chemotherapy, prognosis is limited to 12–15 months. The recent development of immune checkpoint inhibitors (ICIs) encourages optimism that these may represent novel standards-of-care for AGC, with clear clinical benefits. Many clinical trials of combination therapies with cytotoxic agents and molecular-targeted agents, as well as combinations of immunotherapeutic agents, are currently underway for each treatment line. As a result, further improvements in therapeutic outcomes for gastric cancer are anticipated in the near future.

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Conflict of interest statement

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Figures

Figure 1.
Figure 1.. Overview and the results of important gastric cancer clinical trials.
CAPOX: Capecitabine + oxaliplatin; CPS: Combined positive score; FOLFOX: 5-fluorouracil + leucovorin + oxaliplatin; FP: 5-fluorouracil + Cisplatin; Nivo: Nivolumab; OS: Overall survival; PFS: Progression-free survival; PD: Progressive disease; SOX: tegafur/gimeracil/oteracil potassium + oxaliplatin.
Figure 2.
Figure 2.. Recommended chemotherapy regimens for AGC.
Recommended regimens are listed for each line of treatment in the Japanese guidelines. Red letters are ICI. CDDP: Cisplatin; CAPOX: Capecitabine + oxaliplatin; FOLFOX: 5-FU + leucovorin + oxaliplatin; IRI: Irinotecan; PTX: Paclitaxel; RAM: Ramucirumab; Tmab: Trastuzumab; FTD/TPI: Trifluridine/tipiracil; S-1: Tegafur/gimeracil/oteracil potassium; SOX: Tegafur/gimeracil/oteracil potassium + oxaliplatin; T-DXd: Trastuzumab deruxtecan. *This regimen is only available in USA.
See this image and copyright information in PMC

References

    1. Hyuna S, Jacques F, Rebecca L et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. A Cancer Journal for Clinicians 71, 209–249 (2021). - PubMed
    1. Suzanne L, Stephen Hodi F, Julie R et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366(26), 2443–2454 (2012). - PMC - PubMed
    1. Caroline R, Georgina V, Benjamin B et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372(4), 320–330 (2015). - PubMed
    1. Aurelien M, Dung TL, Paolo A et al. Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the phase II KEYNOTE-158 Study. J. Clin. Oncol. 38(1), 1–10 (2020). - PMC - PubMed
    1. Yoon-Koo K, Narikazu B, Taroh S et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10111), 2461–2471 (2017). - PubMed

    2. • This is the first Phase III clinical trial to demonstrate the usefulness of Nivo in gastric cancer.