LBA-4 Initial data from the phase 3 KEYNOTE-811 study of trastuzumab and chemotherapy with or without pembrolizumab for HER2-positive metastatic gastric or gastroesophageal junction (G/GEJ) cancer

Janjigian, Yelena Y.; Kawazoe, Akihito; Weber, Paul; Luo, Suxia; Колеснік, О. П.; Barajas, Olga; Bai, Yuxian; Shen, Lin; Tang, Yong; Wyrwicz, Lucjan; Shitara, Kohei; Qin, Shukui; Cutsem, Éric Van; Tabernero, Josep; Li, L.; Shih, Chie Schin; Bhagia, Pooja; Chung, Hyun Cheol

doi:10.1016/j.annonc.2021.06.011

Cited by 6 publications

(5 citation statements)

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“…Angiogenesis inhibitor blocks proangiogenic pathways, promotes vessel normalization, improves tumor perfusion and oxygenation, restores the hypoxic TME, and enhances drug delivery. Also, angiogenesis inhibitor reshapes the TME: promoting T cell infiltration and DC maturation, enhancing the differentiation towards M1-like macrophage, decreasing the ratio of Treg and MDSC, and alleviating hypoxia-induced PD-L1 chemotherapy was expanded to advanced triple-negative breast cancer (TNBC), esophageal cancer, gastroesophageal junction cancer (GEJC) [55][56][57].…”

Section: Chemotherapy Combined With α-Pd-1mentioning

confidence: 99%

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

et al. 2022

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Antibodies targeting programmed cell death protein-1 (PD-1) or its ligand PD-L1 rescue T cells from exhausted status and revive immune response against cancer cells. Based on the immense success in clinical trials, ten α-PD-1 (nivolumab, pembrolizumab, cemiplimab, sintilimab, camrelizumab, toripalimab, tislelizumab, zimberelimab, prolgolimab, and dostarlimab) and three α-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for various types of cancers. Nevertheless, the low response rate of α-PD-1/PD-L1 therapy remains to be resolved. For most cancer patients, PD-1/PD-L1 pathway is not the sole speed-limiting factor of antitumor immunity, and it is insufficient to motivate effective antitumor immune response by blocking PD-1/PD-L1 axis. It has been validated that some combination therapies, including α-PD-1/PD-L1 plus chemotherapy, radiotherapy, angiogenesis inhibitors, targeted therapy, other immune checkpoint inhibitors, agonists of the co-stimulatory molecule, stimulator of interferon genes agonists, fecal microbiota transplantation, epigenetic modulators, or metabolic modulators, have superior antitumor efficacies and higher response rates. Moreover, bifunctional or bispecific antibodies containing α-PD-1/PD-L1 moiety also elicited more potent antitumor activity. These combination strategies simultaneously boost multiple processes in cancer-immunity cycle, remove immunosuppressive brakes, and orchestrate an immunosupportive tumor microenvironment. In this review, we summarized the synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other therapies. Moreover, we focused on the advances of α-PD-1/PD-L1-based immunomodulatory strategies in clinical studies. Given the heterogeneity across patients and cancer types, individualized combination selection could improve the effects of α-PD-1/PD-L1-based immunomodulatory strategies and relieve treatment resistance.

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Section: Chemotherapy Combined With α-Pd-1mentioning

confidence: 99%

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

et al. 2022

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“…The addition of trastuzumab to standard chemotherapy has been confirmed as the first-line therapy among AGC patients with HER-2 overexpression. Meanwhile, KEYNOTE-811 24 had reported the combination of pembrolizumab, trastuzumab and chemotherapy, which provided a substantial, statistically significant improvement in ORR compared with placebo, trastuzumab, and chemotherapy for HER2-positive advanced gastric cancer patients. In our meta-analysis, it was the first at the rank of ORR in specific positivity group.…”

Section: Discussionmentioning

confidence: 99%

Comparative efficacy and tolerability of targeted and immunotherapy combined with chemotherapy as first-line treatment for advanced gastric cancer: a Bayesian network meta-analysis

Liu

Wong

Xie

et al. 2022

Sci Rep

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The use of target agents and immune checkpoint inhibitors have changed the treatment landscape for AGC in the first-line setting. However, the crosswise comparison between each regimen is rare. Therefore, we estimated the efficacy and safety of targeted therapy or immunotherapy with chemotherapy in AGC patients as the first-line treatment. Included studies were divided into “average” or “specific positivity” group according to whether the patients were selected by a certain pathological expression. We conducted a Bayesian network meta-analysis for all regimens in both groups. In average group, no regimen showed significant improvements in overall survival (OS) and progression free survival (PFS), while pembrolizumab and nivolumab combined with chemotherapy were ranked first and second respectively without an obvious safety difference. In specific positivity group, zolbetuximab plus chemotherapy significantly prolonged OS (HR 0.53, 95% CI 0.36–0.79) and PFS (HR 0.45, 95% CI 0.25–0.81). The top three regimens were zolbetuximab-chemotherapy, trastuzumab plus pertuzuma-chemotherapy and nivolumab-chemotherapy respectively, with no significant safety risk. For average patients, immune checkpoint inhibitor PD-1 plus chemotherapy will be the promising regimen. For patients with overexpression of CLDN18.2, zolbetuximab combined with chemotherapy comes with greater survival benefits, while for patients who have PD-L1 expression with no HER-2 or CLDN18.2 positivity, additional immune checkpoint inhibitor of PD-1 will be a good considered option.

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“…Positive results were recently published for combining the immune checkpoint inhibitor pembrolizumab to trastuzumab and first-line chemotherapy in HER2-positive metastatic esophagogastric cancer [12 ▪ ]. The KEYNOTE-811 trial treated patients in a placebo-controlled randomized trial comparing the addition of pembrolizumab or placebo to chemotherapy using either capecitabine/oxaliplatin or infusional 5-FU/cisplatin combined with trastuzumab.…”

Section: Metastatic Esophagogastric Cancermentioning

confidence: 99%

Advances in the treatment of gastric cancer: 2022–2023

Ilson

2023

Current Opinion in Gastroenterology

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Purpose of review To review 2022–2023 studies in gastric cancer. Recent findings Important studies report the role of laparoscopic surgery in gastric cancer, the activity of immune checkpoint inhibitors in metastatic, locally advanced and adjuvant therapy in gastric cancer, and the effectiveness of zolbetuximab in claudin 18.2-positive metastatic disease. From the Japanese JLSSG0901 Trial, equivalent survival was reported for laparoscopically assisted versus conventional open gastrectomy. Adding nivolumab to adjuvant chemotherapy in resected stage III gastric cancer failed to improve 3-year disease-free survival over chemotherapy alone. Ipilimumab and nivolumab as preoperative therapy in MSI-high gastric cancer resulted in a high rate of pathologic complete response. Trastuzumab added to chemoradiotherapy and surgery in HER2-positive locally advanced esophageal and gastroesophageal junction adenocarcinoma did not improve overall survival over chemoradiotherapy and surgery alone. Adding pembrolizumab to trastuzumab/chemotherapy in metastatic HER2-positive gastric cancer improved antitumor response rate. Addition of zolbetuximab, an antibody targeting claudin 18.2, to first-line chemotherapy in metastatic claudin 18.2-positive gastric cancer improved overall survival. Summary Immune checkpoint inhibition has a role in locally advanced MSI-high and metastatic gastric cancer. Laparoscopic gastrectomy is acceptable in gastric cancer. Zolbetuximab in metastatic gastric cancer will emerge as a new therapy option.

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LBA-4 Initial data from the phase 3 KEYNOTE-811 study of trastuzumab and chemotherapy with or without pembrolizumab for HER2-positive metastatic gastric or gastroesophageal junction (G/GEJ) cancer

Cited by 6 publications

References 0 publications

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

Combination strategies with PD-1/PD-L1 blockade: current advances and future directions

Comparative efficacy and tolerability of targeted and immunotherapy combined with chemotherapy as first-line treatment for advanced gastric cancer: a Bayesian network meta-analysis

Advances in the treatment of gastric cancer: 2022–2023

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