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Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis

  • Authors:
    • Songke Wu
    • Chengshi Wang
    • Shuyun Liu
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Cangxi People's Hospital, Guangyuan, Sichuan 628400, P.R. China, Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of General Surgery and NHC Key Laboratory of Transplant Engineering and Immunology, Frontiers Science Center for Disease‑Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 51
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    Published online on: June 3, 2026
       https://doi.org/10.3892/mco.2026.2960
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Abstract

Optimal first‑line treatments for RAS wild‑type metastatic colorectal cancer (mCRC) remain uncertain, despite the availability of numerous targeted therapies. Direct comparisons between all available regimens are limited, necessitating indirect evidence synthesis. A systematic review and network meta‑analysis of randomized controlled trials (RCTs) comparing first‑line treatments for RAS wild‑type mCRC was conducted in the present study. MEDLINE/PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to September 2025. Primary outcomes included overall survival (OS) and progression‑free survival (PFS), while secondary outcomes included objective response rate (ORR) and safety profiles. Random‑effects network meta‑analyses were performed and treatments were ranked using P‑scores. In total, 15 RCTs involving 6,298 patients and seven primary treatment nodes were included. The network demonstrated high levels of consistency for OS (I2=0%) and moderate heterogeneity for PFS (I2=44.8%) and ORR (I2=40.9%). For OS, both cetuximab + chemotherapy [hazard ratio (HR)=0.853; 95% CI: 0.775‑0.938; P=0.001] and panitumumab + chemotherapy (HR=0.855; 95% CI: 0.738‑0.992; P=0.038) exhibited statistically significant superiority compared with bevacizumab + chemotherapy. Cetuximab + chemotherapy ranked highest for OS (P‑score=0.814) and PFS (P‑score=0.914). Subgroup analysis demonstrated a pronounced tumor sidedness effect. Anti‑EGFR therapy provided a 25.0% reduction in OS risk for left‑sided tumors (HR=0.750; 95% CI: 0.672‑0.836; I2=0%), whereas no survival benefit was observed for right‑sided tumors (HR=1.097; 95% CI: 0.909‑1.325). Anti‑EGFR regimens were associated with higher rates of grade ≥3 toxicities, reaching up to 83.3%, compared with bevacizumab‑based regimens, which fell between 23.4‑68.3%. In the present sensitivity analysis, UDP glucuronosyltransferase family 1 member A1‑guided bevacizumab + 5‑fluorouracil, leucovorin and irinotecan demonstrated favorable outcomes, with OS and PFS P‑scores of 0.932 and 0.992, respectively; however, these findings were derived from a single trial with limited comparability. Overall, anti‑EGFR antibodies combined with chemotherapy demonstrated consistent and statistically significant survival benefits as first‑line treatment for RAS wild‑type mCRC, with cetuximab + chemotherapy ranking as the optimal regimen. Treatment benefit from anti‑EGFR therapy was markedly influenced by primary tumor location, with notable benefit observed in left‑sided tumors and no benefit in right‑sided tumors. These findings support tumor sidedness‑guided treatment selection in clinical practice, favoring anti‑EGFR‑based therapy for left‑sided and bevacizumab‑based therapy for right‑sided RAS wild‑type mCRC.
View Figures

Figure 1

Preferred Reporting Items for
Systematic Reviews and Meta-Analyses diagram of search results and
selections. OS, overall survival; PFS, progression-free survival;
RCTs, randomized controlled trials.

Figure 2

Risk of bias assessment (A) in
individual studies and (B) across the included studies.

Figure 3

Network meta-analysis forest plots
comparing therapies for (A) overall survival, (B) progression-free
survival and (C) objective response rate. HR, hazard ratio;
5-FU/LV, 5-fluorouracil/leucovorin; FOLFOX, 5-fluorouracil,
leucovorin and oxaliplatin; FOLFIRI, 5-fluorouracil, leucovorin and
irinotecan; Cet, cetuximab; Cet(maint.), Cet maintenance; Chemo,
chemotherapy; Bev, bevacizumab.

Figure 4

Treatment ranking by P-scores for (A)
OS, (B) PFS and (C) ORR. OS, overall survival; PFS,
progression-free survival; ORR, objective response rate; FOLFOX,
5-fluorouracil, leucovorin and oxaliplatin; FOLFIRI,
5-fluorouracil, leucovorin and irinotecan; 5-FU/LV,
5-fluorouracil/leucovorin; Cet, cetuximab; Cet(maint.), Cet
maintenance; Chemo, chemotherapy; Bev, bevacizumab.

Figure 5

Subgroup analyses according to tumor
location.
View References

1 

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I and Jemal A: Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 74:229–263. 2024.PubMed/NCBI View Article : Google Scholar

2 

Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, Vignat J, Ferlay J, Murphy N and Bray F: Global burden of colorectal cancer in 2020 and 2040: Incidence and mortality estimates from GLOBOCAN. Gut. 72:338–344. 2023.PubMed/NCBI View Article : Google Scholar

3 

Siegel RL, Wagle NS, Cercek A, Smith RA and Jemal A: Colorectal cancer statistics, 2023. CA Cancer J Clin. 73:233–254. 2023.PubMed/NCBI View Article : Google Scholar

4 

Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, et al: ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 27:1386–1422. 2016.PubMed/NCBI View Article : Google Scholar

5 

Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 369:1023–1034. 2013.PubMed/NCBI View Article : Google Scholar

6 

Bokemeyer C, Köhne CH, Ciardiello F, Lenz HJ, Heinemann V, Klinkhardt U, Beier F, Duecker K, van Krieken JH and Tejpar S: FOLFOX4 plus cetuximab treatment and RAS mutations in colorectal cancer. Eur J Cancer. 51:1243–1252. 2015.PubMed/NCBI View Article : Google Scholar

7 

Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, Heintges T, Lerchenmüller C, Kahl C, Seipelt G, et al: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): A randomised, open-label, phase 3 trial. Lancet Oncol. 15:1065–1075. 2014.PubMed/NCBI View Article : Google Scholar

8 

Venook AP, Niedzwiecki D, Lenz HJ, Innocenti F, Fruth B, Meyerhardt JA, Schrag D, Greene C, O'Neil BH, Atkins JN, et al: Effect of first-line chemotherapy combined with cetuximab or bevacizumab on overall survival in patients with KRAS wild-type advanced or metastatic colorectal cancer: A randomized clinical trial. JAMA. 317:2392–2401. 2017.PubMed/NCBI View Article : Google Scholar

9 

Tsai HL, Huang CW, Lin YW, Wang JH, Wu CC, Sung YC, Chen TL, Wang HM, Tang HC, Chen JB, et al: Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST). Eur J Cancer. 138:19–29. 2020.PubMed/NCBI View Article : Google Scholar

10 

Wang F, He MM, Xiao J, Zhang YQ, Yuan XL, Fang WJ, Zhang Y, Wang W, Hu XH, Ma ZG, et al: A Randomized, open-label, multicenter, phase 3 study of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab in unresectable untreated metastatic colorectal cancer (VITALITY study). Clin Cancer Res. 28:4232–4239. 2022.PubMed/NCBI View Article : Google Scholar

11 

Cremolini C, Schirripa M, Antoniotti C, Moretto R, Salvatore L, Masi G, Falcone A and Loupakis F: First-line chemotherapy for mCRC-a review and evidence-based algorithm. Nat Rev Clin Oncol. 12:607–619. 2015.PubMed/NCBI View Article : Google Scholar

12 

Goldstein DA, Chen Q, Ayer T, Howard DH, Lipscomb J, El-Rayes BF and Flowers CR: First- and second-line bevacizumab in addition to chemotherapy for metastatic colorectal cancer: A United States-based cost-effectiveness analysis. J Clin Oncol. 33:1112–1118. 2015.PubMed/NCBI View Article : Google Scholar

13 

Watanabe J, Muro K, Shitara K, Yamazaki K, Shiozawa M, Ohori H, Takashima A, Yokota M, Makiyama A, Akazawa N, et al: Panitumumab vs bevacizumab added to standard first-line chemotherapy and overall survival among patients with RAS Wild-type, left-sided metastatic colorectal cancer: A randomized clinical trial. JAMA. 329:1271–1282. 2023.PubMed/NCBI View Article : Google Scholar

14 

Qin S, Li J, Wang L, Xu J, Cheng Y, Bai Y, Li W, Xu N, Lin LZ, Wu Q, et al: Efficacy and tolerability of first-line cetuximab plus leucovorin, fluorouracil, and oxaliplatin (FOLFOX-4) versus FOLFOX-4 in patients with RAS wild-type metastatic colorectal cancer: The open-label, randomized, phase III TAILOR trial. J Clin Oncol. 36:3031–3039. 2018.PubMed/NCBI View Article : Google Scholar

15 

Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, et al: Final results from PRIME: Randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol. 25:1346–1355. 2014.PubMed/NCBI View Article : Google Scholar

16 

Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, Hendriks MP, Klaase JM, Kazemier G, Liem MSL, et al: First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): An open-label, multicentre, randomised, controlled, phase 3 study from the Dutch colorectal cancer group. Lancet Oncol. 24:757–771. 2023.PubMed/NCBI View Article : Google Scholar

17 

Arnold D, Lueza B, Douillard JY, Peeters M, Lenz HJ, Venook A, Heinemann V, Van Cutsem E, Pignon JP, Tabernero J, et al: Prognostic and predictive value of primary tumour side in patients with RAS wild-type metastatic colorectal cancer treated with chemotherapy and EGFR directed antibodies in six randomized trials. Ann Oncol. 28:1713–1729. 2017.PubMed/NCBI View Article : Google Scholar

18 

Holch JW, Ricard I, Stintzing S, Modest DP and Heinemann V: The relevance of primary tumour location in patients with metastatic colorectal cancer: A meta-analysis of first-line clinical trials. Eur J Cancer. 70:87–98. 2017.PubMed/NCBI View Article : Google Scholar

19 

Mills EJ, Thorlund K and Ioannidis JPA: Demystifying trial networks and network meta-analysis. BMJ. 346(f2914)2013.PubMed/NCBI View Article : Google Scholar

20 

Lumley T: Network meta-analysis for indirect treatment comparisons. Stat Med. 21:2313–2324. 2002.PubMed/NCBI View Article : Google Scholar

21 

Jansen JP, Trikalinos T, Cappelleri JC, Daw J, Andes S, Eldessouki R and Salanti G: Indirect treatment comparison/network meta-analysis study questionnaire to assess relevance and credibility to inform health care decision making: An ISPOR-AMCP-NPC good practice Task Force report. Value Health. 17:157–173. 2014.PubMed/NCBI View Article : Google Scholar

22 

Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, et al: The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 343(d5928)2011.PubMed/NCBI View Article : Google Scholar

23 

Balduzzi S, Rücker G, Nikolakopoulou A, Papakonstantinou T, Salanti G, Efthimiou O and Schwarzer G: netmeta: An R package for network meta-analysis using frequentist methods. J Stat Softw. 106:1–40. 2023.

24 

Lonardi S, Rasola C, Lobefaro R, Rossini D, Formica V, Scartozzi M, Frassineti GL, Boscolo G, Cinieri S, Di Donato S, et al: Initial panitumumab plus fluorouracil, leucovorin, and oxaliplatin or plus fluorouracil and leucovorin in elderly patients with RAS and BRAF wild-type metastatic colorectal cancer: The PANDA trial by the GONO foundation. J Clin Oncol. 41:5263–5273. 2023.PubMed/NCBI View Article : Google Scholar

25 

Boige V, Blons H, François E, Ben Abdelghani M, Phelip JM, Le Brun-Ly V, Mineur L, Galais MP, Villing AL, Hautefeuille V, et al: Maintenance therapy with cetuximab after FOLFIRI plus cetuximab for RAS wild-type metastatic colorectal cancer: A phase 2 randomized clinical trial. JAMA Netw Open. 6(e2333533)2023.PubMed/NCBI View Article : Google Scholar

26 

Aranda E, García-Alfonso P, Benavides M, Sánchez Ruiz A, Guillén-Ponce C, Safont MJ, Alcaide J, Gómez A, López R, Manzano JL, et al: First-line mFOLFOX plus cetuximab followed by mFOLFOX plus cetuximab or single-agent cetuximab as maintenance therapy in patients with metastatic colorectal cancer: Phase II randomised MACRO2 TTD study. Eur J Cancer. 101:263–272. 2018.PubMed/NCBI View Article : Google Scholar

27 

Modest DP, Martens UM, Riera-Knorrenschild J, Greeve J, Florschütz A, Wessendorf S, Ettrich T, Kanzler S, Nörenberg D, Ricke J, et al: FOLFOXIRI plus panitumumab as first-line treatment of RAS wild-type metastatic colorectal cancer: The randomized, open-label, phase II VOLFI study (AIO KRK0109). J Clin Oncol. 37:3401–3411. 2019.PubMed/NCBI View Article : Google Scholar

28 

Modest DP, Karthaus M, Fruehauf S, Graeven U, Müller L, König AO, Fischer von Weikersthal L, Caca K, Kretzschmar A, Goekkurt E, et al: Panitumumab plus fluorouracil and folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS wild-type metastatic colorectal cancer: The randomized PANAMA trial (AIO KRK 0212). J Clin Oncol. 40:72–82. 2022.PubMed/NCBI View Article : Google Scholar

29 

Liu R, Yin X, Bai Y, Zhong H, Ye F, Wang Q, Liu M, Li N, Deng Y, Wang Y, et al: A140 plus mFOLFOX6 compared with cetuximab plus mFOLFOX6 for first-line RAS wild-type metastatic colorectal cancer: A randomized clinical trial. Eur J Cancer. 226(115566)2025.PubMed/NCBI View Article : Google Scholar

30 

Shi Y, Ba Y, Wang J, Xiong J, Gu K, Chen Y, Zheng Z, Wang Z, Guo W, Cheng Y, et al: First-line treatment of anti-EGFR monoclonal antibody cetuximab β plus FOLFIRI versus FOLFIRI alone in Chinese patients with RAS/BRAF wild-type metastatic colorectal cancer: A randomized, phase 3 trial. Signal Transduct Target Ther. 10(147)2025.PubMed/NCBI View Article : Google Scholar

31 

Misale S, Di Nicolantonio F, Sartore-Bianchi A, Siena S and Bardelli A: Resistance to anti-EGFR therapy in colorectal cancer: From heterogeneity to convergent evolution. Cancer Discov. 4:1269–1280. 2014.PubMed/NCBI View Article : Google Scholar

32 

Parseghian CM, Napolitano S, Loree JM and Kopetz S: Mechanisms of innate and acquired resistance to anti-EGFR therapy: A review of current knowledge with a focus on rechallenge therapies. Clin Cancer Res. 25:6899–6908. 2019.PubMed/NCBI View Article : Google Scholar

33 

Innocenti F, Schilsky RL, Ramírez J, Janisch L, Undevia S, House LK, Das S, Wu K, Turcich M, Marsh R, et al: Dose-finding and pharmacokinetic study to optimize the dosing of irinotecan according to the UGT1A1 genotype of patients with cancer. J Clin Oncol. 32:2328–2334. 2014.PubMed/NCBI View Article : Google Scholar

34 

Jain RK: Normalization of tumor vasculature: An emerging concept in antiangiogenic therapy. Science. 307:58–62. 2005.PubMed/NCBI View Article : Google Scholar

35 

Pietrantonio F, Cremolini C, Petrelli F, Di Bartolomeo M, Loupakis F, Maggi C, Antoniotti C, de Braud F, Falcone A and Iacovelli R: First-line anti-EGFR monoclonal antibodies in panRAS wild-type metastatic colorectal cancer: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 96:156–166. 2015.PubMed/NCBI View Article : Google Scholar

36 

Toffoli G, Sharma MR, Marangon E, Posocco B, Gray E, Mai Q, Buonadonna A, Polite BN, Miolo G, Tabaro G and Innocenti F: Genotype-guided dosing study of FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer. Clin Cancer Res. 23:918–924. 2017.PubMed/NCBI View Article : Google Scholar

37 

Tejpar S, Stintzing S, Ciardiello F, Tabernero J, Van Cutsem E, Beier F, Esser R, Lenz HJ and Heinemann V: Prognostic and predictive relevance of primary tumor location in patients with RAS wild-type metastatic colorectal cancer: Retrospective analyses of the CRYSTAL and FIRE-3 trials. JAMA Oncol. 3:194–201. 2017.PubMed/NCBI View Article : Google Scholar

38 

Franke AJ, Skelton WP, Starr JS, Parekh H, Lee JJ, Overman MJ, Allegra C and George TJ: Immunotherapy for colorectal cancer: A review of current and novel therapeutic approaches. J Natl Cancer Inst. 111:1131–1141. 2019.PubMed/NCBI View Article : Google Scholar

39 

Tabernero J, Vyas M, Giuliani R, Arnold D, Cardoso F, Casali PG, Cervantes A, Eggermont AMM, Eniu A, Jassem J, et al: Biosimilars: A position paper of the European society for medical oncology, with particular reference to oncology prescribers. ESMO Open. 1(e000142)2017.PubMed/NCBI View Article : Google Scholar

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Spandidos Publications style
Wu S, Wang C and Liu S: Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis. Mol Clin Oncol 25: 51, 2026.
APA
Wu, S., Wang, C., & Liu, S. (2026). Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis. Molecular and Clinical Oncology, 25, 51. https://doi.org/10.3892/mco.2026.2960
MLA
Wu, S., Wang, C., Liu, S."Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis". Molecular and Clinical Oncology 25.2 (2026): 51.
Chicago
Wu, S., Wang, C., Liu, S."Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis". Molecular and Clinical Oncology 25, no. 2 (2026): 51. https://doi.org/10.3892/mco.2026.2960
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Spandidos Publications style
Wu S, Wang C and Liu S: Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis. Mol Clin Oncol 25: 51, 2026.
APA
Wu, S., Wang, C., & Liu, S. (2026). Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis. Molecular and Clinical Oncology, 25, 51. https://doi.org/10.3892/mco.2026.2960
MLA
Wu, S., Wang, C., Liu, S."Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis". Molecular and Clinical Oncology 25.2 (2026): 51.
Chicago
Wu, S., Wang, C., Liu, S."Comparative efficacy and safety of first‑line treatments for RAS wild‑type metastatic colorectal cancer: A systematic review and network meta‑analysis". Molecular and Clinical Oncology 25, no. 2 (2026): 51. https://doi.org/10.3892/mco.2026.2960
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