Table 3 Selected key clinical trials of targeted therapies for mGC patients

HER2

ToGA

III

Capecitabine or 5- FU plus cisplatin with vs without trastuzumab as first-line therapy

ORR 47% vs. 35%, P = 0.0017; mOS 13.8 vs. 11.1 months (HR 0.74, 95% CI 0.60–0.91; P = 0.0046); mPFS 6.7 vs 5.5 months (HR 0.71, 95% CI 0.59–0.85; P = 0.0002)

[14]

DESTINY-Gastric01

II

Trastuzumab deruxtecan vs chemotherapy (Irinotecan or Paclitaxel) as third or later-line therapy

ORR 51% vs. 14%, P < 0.001; mOS 12.5 vs. 8.4 months (HR 0.59; 95% CI, 0.39 to 0.88; P = 0.01); mPFS 5.6 vs. 3.5 months (HR 0.47; 95% CI, 0.31 to 0.71)

[132]

DESTINY-Gastric02

II

Trastuzumab deruxtecan as second-line therapy

ORR 41.8%, mPFS 5.6 months (95% CI 4.2–8.3 months); mOS 12.1 months (95% CI 9.4–15.4 months)

[134]

RC48-C008

II

RC48 as third-line therapy and beyond

ORR 24.8% (95% CI 17.5%-33.3%); mPFS 4.1 months (95% CI 3.7–4.9 months); mOS 7.9 months (95% CI 6.7–9.9 months)

[137]

VEGF/ VEGFR

RAINBOW

III

Paclitaxel with vs without ramucirumab as second-line therapy

ORR 28% vs. 16%, P = 0.0001; mOS 9.6 vs 7.4 months (HR 0.81, 95% CI 0.68–0.96; P = 0.017); mPFS 4.4 vs. 2.9 months (HR 0.64, 95% CI 0.54–0.75; P = 0.0001)

[145]

REGARD

III

Ramucirumab vs placebo as second-line therapy

ORR 3% vs. 3%, P = 0.76; mOS 5.2 vs. 3.8 months (HR 0.78, 95% CI 0.61–0.1; P = 0.047); mPFS 2.1 vs. 1.3 months (HR 0.48, 95% CI 0.38–0.62; P < 0.0001)

[144]

RAINBOW-Asia

III

Ramucirumab plus paclitaxel vs placebo plus paclitaxel as second-line therapy

mPFS 4.14 vs 3.15 months (HR 0.765, 95% CI 0.613–0.955, P = 0.0184); mOS 8.71 vs 7.92 months (HR 0.963, 95% CI 0.771–1.203, P = 0.7426)

[146]

Li et al

III

Apatinib vs placebo as third or later-line therapy

ORR 2.84% vs. 0.00%, P = 0.17; mOS 6.5 vs. 4.7 months (HR 0.71, 95% CI 0.54–0.94; P = 0.015); mPFS 2.6 vs. 1.8 months (HR 0.44, 95% CI 0.33–0.6; P < 0.001)

[152]

ANGEL

III

Apatinib + BSC vs placebo + BSC as third or later-line therapy

In ≥ 3rd-line patients: mOS 5.78 vs. 5.13 months (HR = 0.93; 95% CI 0.74–1.15; P = 0.4850); mPFS 2.83 vs. 1.77 months (HR = 0.57; 95% CI 0.46–0.79; P < 0.0001); ORR 6.87% vs. 0%, P = 0.0020; DCR 42.37% vs. 13.08%, P < 0.0001

In ≥ 4th-line patients: mOS 6.43 vs. 4.73 months (HR = 0.65; 95% CI 0.46–0.92; P = 0.0195); mPFS 3.52 vs 1.71 moths (HR = 0.38; 95% CI 0.27–0.53; P < 0.0001)

[153]

CLDN18.2

SPOTLIGHT

III

Zolbetuximab + mFOLFOX6 vs placebo + mFOLFOX6 as first-line therapy in patients with CLDN18.2-positive and HER-2-negative advanced gastric or GEJ cancer

mPFS 10.61 vs. 8.67 months (HR 0.751, P = 0.0066) mOS 18.23 vs. 15.54 months (HR 0.750, P = 0.0053)

[162]

GLOW

III

Zolbetuximab + CAPOX vs placebo + CAPOX as first-line therapy in patients with CLDN18.2-positive and HER-2-negative advanced gastric or GEJ cancer

mPFS (8.21 vs 6.80 months, HR 0.687, P = 0.0007) and mOS (14.39 vs. 12.16 months, HR 0.771, P = 0.0118)

[163]

FGFR

FIGHT

II

Bemarituzumab + mFOLFOX6 vs placebo + mFOLFOX6 as first-line therapy

ORR 47% vs. 33%; mOS not reached vs. 12.9 months (HR 0.58, 95% CI 0.35–0.95; P = 0.027); mPFS 9.5 vs. 7.4 months (HR 0.68, 95% CI 0.44–1.04; P = 0.073)

[172]