Gastric cancer is the fifth most common malignancy worldwide and one of the main causes of cancer-related death. While surgical treatment is the only curative option for early disease, many have inoperable or advanced disease at diagnosis. Treatment in this case would be a combination of chemotherapy and immunotherapy. Gastro-esophageal (GEJ) and gastric cancer (GC) genetic profiling with molecular diagnostic techniques has significantly changed the therapeutic landscape in advanced cancers. The identification of key players in GEJ and GC survival and proliferation, such as human epidermal growth factor 2 (HER2), vascular endothelial growth factor (VEGF), and programmed cell death protein 1 (PD-1)/programmed cell death ligand-1 (PD-L1), has allowed for the individualization of advanced cancer treatment and significant improvement in overall survival and progression-free survival of patients.
Target | Trial | Agent | Experimental Arm | Control Arm | Primary Endpoints | Results (Experimental vs. Control) | Reference in the Text |
---|---|---|---|---|---|---|---|
HER2 | ToGA | Trastuzumab | Trastuzumab + chemotherapy (cisplatin + 5-FU or cisplatin + capecitabine) | Cisplatin/5-FU or cisplatin/capecitabine | OS | OS: 13.8 vs. 11.1 months (HR 0.74; 95% CI 0.60–0.91) | [15] |
JACOB | Pertuzumab + trastuzumab | Pertuzumab + Trastuzumab + chemotherapy (cisplatin or capecitabine or 5-FU) | Trastuzumab + chemotherapy (cisplatin or capecitabine or 5-FU) | OS | OS: 17.5 vs. 14.2 months (HR 0.84; 95% CI 0.71–1.00) | [20] | |
LOGiC | Lapatinib | Lapatinib + chemotherapy (capecitabine + oxaliplatin) | Capecitabine + oxaliplatin | OS | OS: 12.2 vs. 10.5 months (HR 0.91; 95% CI 0.73–1.12) | [21] | |
VEGF | AVAGAST | Bevacizumab | Bevacizumab + chemotherapy (cisplatin + capecitabine or cisplatin + 5-FU) | Cisplatin + capecitabine or cisplatin + 5-FU | OS | OS: 12.1 vs. 10.1 months (HR 0.87; 95% CI 0.73–1.03) | [22] |
VEGFR-2 | RAINFALL | Ramucirumab | Ramucirumab + chemotherapy (cisplatin + capecitabine or cisplatin + 5-FU) | Cisplatin + capecitabine or cisplatin + 5-FU | PFS | PFS: 6.7 vs. 5.4 months (HR 0.753; 85% CI 0.607–0.935) | [23] |
Trial | Agent | Experimental Arm | Control Arm | Primary Endpoints | Results (Experimental vs. Control) | Reference in the Text |
---|---|---|---|---|---|---|
CheckMate-649 | Nivolumab | Nivolumab + chemotherapy (XELOX or FOLFOX) | XELOX or FOLFOX | OS and PFS in patients with CPS ≥ 5 | OS: 14.4 vs. 11.1 months (HR 0.71; 98.4% CI 0.59–0.86) PFS: 7.7 vs. 6.05 months (HR 0.68; 98% CI 0.56–0.81) |
[37][35] |
ORIENT-16 | Sintilimab | Sintilimab + chemotherapy (CAPOX) | CAPOX | OS in patients with CPS ≥ 5 and OS in all patients | OS in patients with CPS ≥ 5: 18.4 vs. 12.9 months (HR 0.660; 95% CI 0.505–0.864) OS in all patients: 15.2 vs. 12.3 months (HR 0.766; 95% CI 0.626–0.936) |
[39][36] |
RATIONALE 305 | Tislelizumab | Tislelizumab + chemotherapy (CAPOX or cisplatin + 5-FU) | CAPOX or cisplatin + 5-FU | OS | OS: 17.2 vs. 12.6 months (HR 0.74; 95% CI 0.59–0.94) | [40][37] |
ATTRACTION-4 | Nivolumab | Nivolumab + chemotherapy (SOX or CAPOX) | SOX or CAPOX | PFS and OS | PFS: 10.45 vs. 8.34 months (HR 0.68; 98.51% CI 0.51–0.90) OS: 17.45 vs. 17.15 months (HR 0.90; 95% CI 15.67–20.83) |
[41][38] |
KEYNOTE-859 | Pembrolizumab | Pembrolizumab + chemotherapy (cisplatin + 5-FU or CAPOX) | Cisplatin + 5-FU or CAPOX | OS | OS: 12.9 vs. 11.5 months (HR 0.78; 95% CI 0.70–0.87) | [42][39] |
KEYNOTE-062 | Pembrolizumab | Pembrolizumab or pembrolizumab + chemotherapy (cisplatin + 5-FU or cisplatin + capecitabine) |
Cisplatin + 5-FU or cisplatin + capecitabine | OS and PFS in patients with CPS ≥ 1 | Pembrolizumab vs. chemotherapy OS: 10.6 vs. 11.1 months (HR 0.91; 99.2% CI 0.69–1.18) PFS: 2.0 vs. 6.4 months (HR 1.66; 95% CI 1.37–2.01) Pembrolizumab + chemotherapy vs. chemotherapy: OS: 12.5 vs. 11.1 months (HR 0.85; 95% CI 0.70–1.03) PFS: 6.9 vs. 6.4 months (HR 0.84; 95% CI 0.70–1.02) |
[43][40] |
KEYNOTE-811 | Trastuzumab + pembrolizumab | Trastuzumab + pembrolizumab + chemotherapy (cisplatin + 5-FU or CAPOX) | Cisplatin + 5-FU or CAPOX | OS and PFS | Interim results ORR: 74.4% vs. 51.9% | [48][41] |
Trial | Agent | Experimental Arm | Control Arm | Primary Endpoint | Results (Experimental vs. Control) | Reference in the Text |
---|---|---|---|---|---|---|
SPOTLIGHT | Zolbetuximab | Zolbetuximab + chemotherapy (mFOLFOX6) | mFOLFOX6 | PFS | PFS: 10.61 vs. 8.67 months (HR 0.751; 95% CI 0.589–0.941) | [62][55] |
GLOW | Zolbetuximab | Zolbetuximab + chemotherapy (CAPOX) | CAPOX | PFS | PFS: 8.21 vs. 6.80 months (HR 0.687; 95% CI 0.544–0.866) | [63][56] |