Adoptive T-cell therapy (ACT), a method that involves reinfusing T-cells that were expanded ex vivo from patient-derived T-cells, looks promising in terms of overall survival (OS) and progression-free survival (PFS) for patients with advanced colorectal cancer (CRC), especially in comparison to currently available second- and third-line treatments.
Therefore, a team of researchers conducted a systematic literature review to determine the potential therapeutic effectiveness of ACT in patients with advanced CRC. Their findings were published in The Oncologist.
The review included 15 studies published within the last 10 years. Additional criteria were type of study, age of participants, stage of disease, and all participants had undergone a first-line treatment for advanced CRC. The included studies evaluated ACT in 1 of 3 settings:
- ACT in combination with chemotherapy vs supportive care, no treatment, or placebo
- ACT in combination with chemotherapy vs chemotherapy alone
- ACT in combination with chemotherapy
“Currently, no phase III clinical trials of ACT have been resulted in advanced CRC,” the researchers reported. Available data from phase 1 and phase 2 clinical trials suggest that OS and PFS may be prolonged in patients with advanced CRC, and ACT is generally well-tolerated in this patient population.
Three of 5 ACT trials reported median OS estimates of longer than 14 months, which compared favorably with the 5-month median OS estimates for standard approved therapies in the second-/third-line setting. Additionally, all 7 trials that reported PFS had median PFS estimates that exceeded 4.5 months, compared with 1.7 months for the standard therapies.
For perspective on the toxicity results of this review, clinical trial data from a study of FOLFOX6 and FOLFIRI with bevacizumab or cetuximab as a first-line treatment for Ras-wild type mCRC showed incidence of severe adverse events (SAEs) was 53%. By comparison, SAE incidence was only 30% in patients receiving ACT on protocol, although these patients were already at greater risk for treatment-related adverse events.
“This suggests that ACT tolerance compares favorably to current chemotherapy-based standards of care,” the researchers concluded.
However, despite the promise of ACT in the treatment of patients with advanced CRC, additional stage I/II clinical trials are needed to provide more evidence about its safety and efficacy.
Study limitations were a lack of randomized trials included in the review made comparing the results between different experimental groups difficult, as well as small sample sizes for each study ruled out the possibility of combining results for statistical analysis. The over results could be confounded by the inclusion of IL-2, hyperthermia, and anti-PD-1in some of the studies.
Juat DJ, Hachey SJ, Billimek J, et al. Adoptive T-cell therapy in advanced colorectal cancer: a systematic review. Oncologist. 2022;27(3):210-219. doi:10.1093/oncol/oyab038