Table 2.
Immunotherapies for advanced gastric cancer patients
|
Ref.
|
Drug(s)
|
Number of patients
|
Study phase
|
ORR (%)
|
Median OS (months)
|
Median PFS (months)
|
Results
|
| Muro et al[52] | Pembrolizumab | 39 | 1b | 33 | 11.4 | 1.8 | Pembrolizumab demonstrated a reasonable safety profile and potential antitumor efficacy in metastatic PD-L1-positive GC, warranting further exploration in phase 2 and 3 studies |
| Fuchs et al[53] | Pembrolizumab | 259 | 2 | 15.5 | 5.6 | 2.0 | Pembrolizumab is a potential new therapy option for AGC or AGEJC that has progressed following second-line treatment, demonstrating high and persistent responses. Pembrolizumab has a mechanism of action, duration of response, and toxicity profile that differs from and does not overlap with conventional treatment for gastroesophageal adenocarcinoma |
| Shitara et al[54] | Pembrolizumab vs Paclitaxel | 395 | 3 | - | 9.1/8.3 (Pem/Pac) | 1.5/4.1 (Pem/Pac) | When compared to Paclitaxel, Pembrolizumab did not significantly improve overall survival when administered as a second-line therapy for AGC or AGEJC with PD-L1 CPS of 1 or higher |
| Bang et al[55] | Pembrolizumab vs Pembrolizumab plus chemotherapy | 56 | 2 | 25.8/60.0 (Pem/Pem+Chem) | 13.8/20.7 (Pem/Pem+Chem) | 3.3/6.6 (Pem/Pem+Chem) | Pembrolizumab combined chemotherapy showed acceptable tolerability and potential anticancer efficacy in AGC or AGEJC, independent of PD-L1 expression. In patients with PD-L1 CPS ≥ 1, pembrolizumab monotherapy revealed good antitumor efficacy and acceptable safety |
| Kawazoe et al[56] | Pembrolizumab plus chemotherapy | 54 | 2b | 72.2 | Not reached | 9.4 | For the first-line treatment of AGC or AGEJC patients, chemotherapy with Pembrolizumab shown good effectiveness and a tolerable toxicity profile |
| Kawazoe et al[57] | Pembrolizumab plus Lenvatinib | 29 | 2 | 69.0 | Not reached | 7.1 | In patients with AGC, the combination of Lenvatinib and Pembrolizumab demonstrated promising anti-tumor effectiveness while maintaining a tolerable safety profile |
| Shitara et al[58] | Pembrolizumab vs Pembrolizumab plus chemotherapy vs chemotherapy | 763 | 3 | - | 10.6/11.1 (Pem/chem) CPS ≥ 1; 17.0/10.8 CPS ≥ 10 | 6.9/6.4 (Pem/chem) | In individuals with untreated AGC or AGEJC, Pembrolizumab was shown to be noninferior to chemotherapy, with less adverse effects. Pembrolizumab alone or in combination with chemotherapy did not outperform treatment in terms of OS and PFS |
| Kwon et al[60] | Pembrolizumab | 18 | 2 | 55.6 | - | - | A subset of MSI-H GC patients with certain immunological responses at baseline, such as stronger TMB, abundant T cell infiltration, more TCR clonal diversity, and less stem-like exhausted T cells, may not require anything more than anti-PD-1 monotherapy |
| Yamaguchi et al[63] | Pembrolizumab plus SOX vs Pembrolizumab plus SP | 100 | 2b | 72.2/80.4 | 16.9/17.1 | 9.4/8.3 | In Japanese patients with PD-L1 positive, HER-2 negative AGC or AGEJC, the combination of Pembrolizumab plus SOX or SP as first-line treatment indicated high efficacy and reasonable tolerability |
| Lee et al[64] | Pembrolizumab plus Trastuzumab plus Capecitabine plus Cisplatin | 43 | 1b/2 | 76.7 | 19.3 | 8.6 | The use of a quadruplet combination as first-line therapy (Pembrolizumab plus Trastuzumab plus Capecitabine plus Cisplatin) resulted in tumor decrease in HER-2-positive AGC |
| Satake et al[65] | Pembrolizumab vs Pembrolizumab plus chemotherapy vs chemotherapy | 187 | 3 | 22.6/37.7 (Pem/chem); 26.9/31.8 (PD-L1 CPS ≥ 10) | 22.7/13.8 (Pem/chem); 28.5/14.8 (PD-L1 CPS ≥ 10) | 4.1/6.5 (Pem/chem); 7.2/6.9 (PD-L1 CPS ≥ 10) | Pembrolizumab monotherapy was related with statistically better OS results in patients with AGC or AGEJC with PD-L1 CPS ≥ 1 and CPS ≥ 10 tumors as compared to chemotherapy alone. When compared to chemotherapy, Pembrolizumab monotherapy had a better tolerability profile |
| Janjigian et al[66] | Nivolumab plus Ipilimumab vs Nivolumab | 160 | 1/2 | 24/12 (Niv+Ipi/Niv) | 6.9/6.2 (Niv+Ipi/Niv) | 1.6/1.4 (Niv+Ipi/Niv) | Nivolumab and Nivolumab in combination with Ipilimumab provide a viable treatment option for individuals with AGEJC |
| Kang et al[67] | Nivolumab vs placebo | 493 | 3 | 11.2/0.0 | 5.32/4.14 | 1.61/1.45 | Nivolumab might be a potential therapy option for people with AGC or AGEJC who have been highly pretreated |
| Boku et al[69] | Nivolumab plus SOX vs Nivolumab plus CapeOX | 77 | 2 | 57.1/76.5 | Not reached | 9.7/10.6 | In these individuals, Nivolumab in conjunction with SOX or CapeOX was well tolerated and showed potential efficacy |
| Nakajima et al[71] | Nivolumab plus Paclitaxel plus Ramucirumab | 43 | 1/2 | 37.2 | 13.1 | 5.1 | As a second-line treatment for AGC, Nivolumab in combination with Paclitaxel and Ramucirumab shown promising antitumor activity with tolerable tolerability |
| Janjigian et al[72] | Nivolumab plus chemotherapy vs chemotherapy | 1,581 | 3 | 51/41 | 14.4/11.1 | 7.7/6.1 | Nivolumab in conjunction with chemotherapy is being considered as a new standard first-line treatment for these individuals |
| Shah et al[73] | Andecaliximab plus Nivolumab vs Nivolumab | 141 | 2 | 10/7 | 7.1/5.9 | - | When compared to Nivolumab alone, the combination of Andecaliximab and Nivolumab exhibited a favorable safety profile but did not boost efficacy in these people |
| Kang et al[74] | Nivolumab plus oxaliplatin-based chemotherapy vs placebo plus oxaliplatin-based chemotherapy | 724 | 2/3 | - | 17.45/17.15 | 10.45/8.34 | In these patients, Nivolumab in conjunction with oxaliplatin-based chemotherapy improved PFS but not OS |
| Bang et al[76] | Avelumab vs chemotherapy | 371 | 3 | 2.2/4.3 | 4.6/5.0 | 1.4/2.7 | As compared to chemotherapy, treating these patients in the third-line setting with single-agent Avelumab did not improve OS or PFS. Avelumab, on the other hand, had a more manageable toxicity profile than chemotherapy |
| Moehler et al[77] | Avelumab vs chemotherapy | 499 | 3 | - | 10.4/10.9 | - | In patients with AGC or AGEJC in general, or in a specified PD-L1-positive population, Avelumab maintenance therapy did not give a superior OS when compared to continuing chemotherapy |
AGC: Advanced gastric cancer; AGEJC: Advanced gastroesophageal junction cancer; CapeOX: Capecitabine plus oxaliplatin C; Chem: Chemotherapy; CPS: Combined positive score; HER-2: Human epidermal growth factor receptor 2; MIS-H: High microsatellite instability; Niv: Nivolumab; Niv+Ipi: Nivolumab plus Ipilimumab; ORR: Objective response rate; OS: Overall survival; Pac: Paclitaxel; Pem: Pembrolizumab; PD-L1: Program cell death ligand 1; PFS: Progression-free survival; SOX: S-1 plus oxaliplatin; SP: S-1 and cisplatin; TCR: T-cell receptor; TMB: Tumor mutational burden.