Clinical advances in later-line therapy for metastatic or refractory colorectal cancer

Table 2 Targeted therapy involving gene mutations or gene amplifications

Trial name/Ref.	Type	Sample size	Regimen	Dosage and administration (combination therapy group)	mPFS (months, 95%CI)	Hazard ratio (95%CI); P value	mOS (months, 95%CI)	Hazard ratio (95%CI); P value	ORR (%); P value
Fakih et al[37], 2023	KRAS G12C	160	Sotorasib + panitumumab	Sotorasib: 960 mg/240 mg qd; panitumumab: 6 mg/kg q2w	5.6 (4.2–6.3)1 vs 3.9 (3.7–5.8)2 vs 2.2 (1.9–3.9)3	0.49 (0.30–0.80)4; P = 0.006			26.4%1 vs 0.0%3
Pietrantonio et al[38], 2025	KRAS G12C	160	Sotorasib + panitumumab	Sotorasib: 960 mg/240 mg qd; panitumumab: 6 mg/kg q2w	5.7 (4.2–7.5)1 vs 4.01 (3.7–5.9)2 vs 2.04 (1.9–3.9)3	0.45 (0.29– 0.72)4	NE (8.61–NE)1 vs 11.9 (7.52–NE)2 vs 10.3 (7.00–NE)3	0.70 (0.41–1.18)4; P = 0.20	30.2%1 vs 7.5%2 vs 1.9%3
Kuboki et al[39], 2024	KRAS G12C	40	Sotorasib + panitumumab	Sotorasib: 960 mg qd; panitumumab: 6 mg/kg q2w	5.7 (4.2–7.7)		15.2 (12.5–NE)		30%
KRYSTAL-1 trial[40], 2024	KRAS G12C	94	Adagrasib + cetuximab	Adagrasib: 600 mg bid; cetuximab: 400 mg/m2 d1, then 250 mg/m2 qw or 500 mg/m2 q2w	6.9 (5.7–7.4)		15.9 (11.8–18.8)		34%
Li et al[41], 2026 (involves 2 trials)	KRAS G12C	JAB-21822-1007: 47; JAB-21822-1002: 44	Glecirasib + cetuximab; glecirasib	Glecirasib: 800 mg qd; cetuximab: 400 mg/m2 d1, then 250 mg/m2 qw or 500 mg/m2 q2w	6.9 (5.4–6.9); 5.6 (4.1–7.0)		19.3 (13.1–NE); 16.0 (8.8–26.3)		50%; 23%
BEACON CRC[69], 2019	BRAF V600E	665	Encorafenib + binimetinib + cetuximab	Encorafenib: 300 mg qd q4w; binimetinib: 45 mg bid q4w; cetuximab: 400 mg/m2 d1, then 250 mg/m2 qw	4.3 (4.1–5.2)5 vs 4.2 (3.7–5.4)6 vs 1.5 (1.5–1.7)7	0.38 (0.29–0.49)8; P < 0.001	9.0 (8.0–11.4)5 vs 8.4 (7.5–11.0)6 vs 5.4 (4.8–6.6)7	0.52 (0.39–0.70)8; P < 0.001	26%5 vs 20%6 vs 2%7
Morris et al[99], 2025	BRAF V600E, MSS	26	Encorafenib + cetuximab + nivolumab	Encorafenib: 300 mg qd; cetuximab: 500 mg/m2 q2w; nivolumab: 480 mg q4w	7.4 (5.6–9.6)		22.0 (11.2–25.8)		42%
Wei et al[100], 2025	BRAF V600E, MSS	12	Vemurafenib + cetuximab + camrelizumab	Cetuximab: 500 mg/m2 q2w; vemurafenib: 960 mg qd/bid; camrelizumab: 200 mg q2w	3.47 (1.76–5.18)		7.19 (4.97–NA)		33.30%
Fu et al[32], 2023	HER2	20	Pyrotinib + trastuzumab	Pyrotinib: 400 mg qd; trastuzumab: 8 mg/kg d1, then 6 mg/kg q3w	3.4 (1.8–4.3)				22.20%
Yang et al[33], 2025	HER2	20	Pyrotinib + trastuzumab	Pyrotinib: 400 mg qd; trastuzumab: 8 mg/kg d1, then 6 mg/kg q3w	6.2 (0.42–11.98)		21.1 (15.84–26.36)		23.50%
MOUNTAINEER[34,35], 2023	HER2	117	Tucatinib + trastuzumab	Tucatinib: 300 mg bid; trastuzumab: 8 mg/kg d1, then 6 mg/kg q3w	8.1 (4.2–10.2)		23.9 (18.7–28.3)		39.30%
Raghav et al[36], 2025	HER2	54	Trastuzumab + pertuzumab vs cetuximab + irinotecan	Trastuzumab: 8 mg/kg d1, then 6 mg/kg q3w; pertuzumab: 840 mg d1, then 420 mg q3w	4.7 (1.9–7.6) vs 3.7 (1.6–6.7)	0.79 (0.43–1.45); P = 0.44	NR (19.4–NR) vs 24.7 (15.2–33.8)	0.56 (0.25–1.29); P = 0.17	34.6% vs 28.0%
Xu et al[72], 2023	HER2	21	Trastuzumab + irinotecan	Trastuzumab: 8 mg/kg d1, then 6 mg/kg q3w; irinotecan: 120 mg/m2 d1, 8 q3w	4.3 (2.7–5.9)		17.9 (11.8–24.1)		33.30%
DESTINY-CRC01[108], 2021	HER2	78	Trastuzumab deruxtecan	Trastuzumab deruxtecan: 6.4 mg/kg q3w	6.9 (4.1–not evaluable)9		5.4 (IQR 4.1–8.3)		45.3%9

¹Sotorasib-panitumumab group (960 mg).

²Sotorasib-panitumumab group (240 mg).

³The standard-care group.

⁴Sotorasib-panitumumab group (960 mg) compared with the standard-care group.

⁵Encorafenib + binimetinib + cetuximab.

⁶Encorafenib + cetuximab.

⁷Cetuximab + irinotecan/FOLFIRI.

⁸Encorafenib + binimetinib + cetuximab group compared with the cetuximab + irinotecan/FOLFIRI group.

⁹IHC 3+ or IHC 2+ and ISH-positive.

CI: Confidence interval; IQR: Interquartile range; mOS: Median overall survival; mPFS: Median progression-free survival; NA: Not applicable; NE: Not estimable; NR: Not reached; ORR: Objective response rate.