Vaccine-Based Immunotherapy for Metastatic Colorectal Cancer: A Systematic Review

Penulis

  • Sesa Amelia Faculty of Medicine at Diponegoro University and Mohammad Noer Hospital in Pamekasan, Indonesia
  • Asya Mathlubaa Department of Internal Medicine, Latin American School of Medicine, Havana, Cuba
  • Harzalina Zilfi Amly RSUD Jemaja, Riau, Indonesia
  • Christin Yosefin Jacobs RSAL Dr.Mintohardjo/Universitas Sam Ratulangi, North Sulawesi, Indonesia
  • Kurnia Halim Department of Internal Medicine, Tarumanagara University, Jakarta, Indonesia
  • Timotius Ivan Heriawan Department of Internal Medicine, Universitas Kristen Duta Wacana, Yogyakarta, Indonesia
  • Vincent Guantoro Department of Internal Medicine, Universitas Sriwijaya, Palembang, Indonesia
  • Hesti Andika Putri Department of Internal Medicine, Universitas Riau, Riau, Indonesia

DOI:

https://doi.org/10.19166/med.v14i3.10166

Kata Kunci:

Colorectal cancer, Immunotherapy, Metastasis, Vaccine

Abstrak

Background: Metastatic colorectal cancer (mCRC) remains a therapeutic challenge, particularly in microsatellite stable (MSS) tumors, which are largely unresponsive to current immunotherapy approaches. Vaccine-based immunotherapy offers a strategy to elicit tumor-specific immune responses in these immunologically “cold” tumors. However, clinical results have been mixed, and the efficacy and safety of cancer vaccines in mCRC remain to be clarified.

Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. Randomized controlled trials (RCTs) evaluating vaccine-based immunotherapy in mCRC were identified from PubMed, EMBASE, and Scopus as of May 2, 2025. Eligible studies included human subjects with mCRC receiving vaccine therapy with or without additional treatments, compared to standard or placebo regimens. The primary outcomes were overall survival (OS) and progression-free survival (PFS); safety was assessed by the incidence of grade ≥3 treatment-related adverse events.

Result: Five RCTs comprising 804 patients met inclusion criteria. Pooled analysis showed a trend toward improved OS with vaccine-based immunotherapy (HR 0.81; 95% CI, 0.65–1.00; p = 0.05; I² = 0%), and a modest, non-significant improvement in PFS (HR 0.80; 95% CI, 0.62–1.05; p = 0.07; I² = 0%). The incidence of severe adverse events was lower with vaccine-based therapies (RR 0.31; 95% CI, 0.02–6.09; p = 0.23; I² = 90%).

Conclusions: Vaccine-based immunotherapy in mCRC demonstrates potential clinical benefit, particularly in prolonging survival with a favorable safety profile. Further biomarker-driven studies are needed to optimize patient selection and therapeutic combinations.

Referensi

1. Ilyas MIM. Epidemiology of stage IV colorectal cancer: trends in the incidence, prevalence, age distribution, and impact on life span. Clin Colon Rectal Surg. 2024 Mar;37(2):57–61. https://doi.org/10.1055/s-0043-1761447

2. Salvà F, Saoudi N, Rodríguez M, Baraibar I, Ros J, García A, et al. Determinants of metastatic colorectal cancer with permanent liver-limited disease. Clin Colorectal Cancer. 2024 Sep;23(3):207–14. https://doi.org/10.1016/j.clcc.2024.05.010

3. Boukouris AE, Theochari M, Stefanou D, Papalambros A, Felekouras E, Gogas H, et al. Latest evidence on immune checkpoint inhibitors in metastatic colorectal cancer: a 2022 update. Crit Rev Oncol Hematol. 2022 May;173:103663. https://doi.org/10.1016/j.critrevonc.2022.103663

4. Quintanilha JCF, Graf RP, Fisher VA, Oxnard GR, Ellis H, Panarelli N, et al. Comparative effectiveness of immune checkpoint inhibitors vs chemotherapy in patients with metastatic colorectal cancer with measures of microsatellite instability, mismatch repair, or tumor mutational burden. JAMA Netw Open. 2023 Jan 23;6(1):e2252244. https://doi.org/10.1001/jamanetworkopen.2022.52244

5. Liu D, Che X, Wang X, Ma C, Wu G. Tumor vaccines: unleashing the power of the immune system to fight cancer. Pharmaceuticals (Basel). 2023 Sep 29;16(10):1384. https://doi.org/10.3390/ph16101384

6. Ni L. Advances in mRNA-based cancer vaccines. Vaccines (Basel). 2023 Oct 16;11(10):1599. https://doi.org/10.3390/vaccines11101599

7. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. https://doi.org/10.1136/bmj.n71

8. Mettu NB, Ou FS, Zemla TJ, Halfdanarson TR, Lenz HJ, Breakstone RA, et al. Assessment of capecitabine and bevacizumab with or without atezolizumab for the treatment of refractory metastatic colorectal cancer: a randomized clinical trial. JAMA Netw Open. 2022 Feb 18;5(2):e2149040. https://doi.org/10.1001/jamanetworkopen.2021.49040

9. Diaz LA, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, et al. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. Lancet Oncol. 2022 May;23(5):659–70. https://doi.org/10.1016/S1470-2045(22)00197-8

10. Schoenfeld JD, Giobbie-Hurder A, Ranasinghe S, Kao KZ, Lako A, Tsuji J, et al. Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2022 Feb;23(2):279–91. https://doi.org/10.1016/s1470-2045(21)00658-6

11. Ducreux M, Tabernero J, Grothey A, Arnold D, O’Dwyer PJ, Gilberg F, et al. Clinical and exploratory biomarker findings from the MODUL trial (Cohorts 1, 3 and 4) of biomarker-driven maintenance therapy for metastatic colorectal cancer. Eur J Cancer. 2023 May;184:137–50. https://doi.org/10.1016/j.ejca.2023.01.023

12. Taïeb J, Bouche O, André T, Le Malicot K, Laurent-Puig P, Bez J, et al. Avelumab vs standard second-line chemotherapy in patients with metastatic colorectal cancer and microsatellite instability: a randomized clinical trial. JAMA Oncol. 2023 Oct 1;9(10):1356–63. https://doi.org/10.1001/jamaoncol.2023.2761

13. Morse MA, Niedzwiecki D, Marshall JL, Garrett C, Chang DZ, Aklilu M, et al. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann Surg. 2013 Dec;258(6):879–86. https://doi.org/10.1097/sla.0b013e318292919e

14. Hanna MG. Immunotherapy with autologous tumor cell vaccines for treatment of occult disease in early stage colon cancer. Hum Vaccin Immunother. 2012 Aug;8(8):1156–60. https://doi.org/10.4161/hv.20740

15. Oh DY, Rokutanda N, Żotkiewicz M, He P, Stocks J, Johnson ML. Delayed separation of Kaplan-Meier curves is commonly observed in studies of advanced/metastatic solid tumors treated with anti-PD-(L)1 therapy: systematic review and meta-analysis. Target Oncol. 2025 Jan;20(1):45–56. https://doi.org/10.1007/s11523-024-01108-2

16. Gulley JL, Arlen PM, Tsang KY, Yokokawa J, Palena C, Poole DJ, et al. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res. 2008 May 15;14(10):3060–9. https://doi.org/10.1158/1078-0432.ccr-08-0126

17. Shiraishi K, Okada M, Yamamoto S, Matsubara Y, Masuishi T, Shimozaki K, et al. The efficacy and safety of FOLFOX therapy for advanced esophageal squamous cell carcinoma. Sci Rep. 2025 Mar 7;15(1):8031. http://dx.doi.org/10.1038/s41598-025-92657-7

18. Zhang X, Duan R, Wang Y, Liu X, Zhang W, Zhu X, et al. FOLFIRI (folinic acid, fluorouracil, and irinotecan) increases not efficacy but toxicity compared with single-agent irinotecan as a second-line treatment in metastatic colorectal cancer patients: a randomized clinical trial. Ther Adv Med Oncol. 2022;14:17588359211068737. https://doi.org/10.1177/17588359211068737

19. Ott PA, Hu-Lieskovan S, Chmielowski B, Govindan R, Naing A, Bhardwaj N, et al. A phase Ib trial of personalized neoantigen therapy plus anti-PD-1 in patients with advanced melanoma, non-small cell lung cancer, or bladder cancer. Cell. 2020 Oct 15;183(2):347–62.e24. https://doi.org/10.1016/j.cell.2020.08.053

Diterbitkan

2025-06-09

Cara Mengutip

Amelia, S., Mathlubaa, A., Amly, H. Z., Jacobs, C. Y., Halim, K., Heriawan, T. I., … Putri, H. A. (2025). Vaccine-Based Immunotherapy for Metastatic Colorectal Cancer: A Systematic Review. Medicinus, 14(3), 260–269. https://doi.org/10.19166/med.v14i3.10166

Terbitan

Bagian

Articles