KEY TAKEAWAYS
- The AVETUXIRI phase 2 trial aimed to characterize the systemic immune response and its role in response to immunotherapy in pts with MSS chemorefractory mCRC.
- The TH17 and NKT cell frequency alterations may impact the tumor response and survival in MSS mCRC.
Clinical efficacy and safety of avelumab (AVE), cetuximab (CET) and irinotecan (IRI) have previously been reported for the treatment of chemo refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC).
Elena BENIDOVSKAYA and the team aimed to characterize the systemic immune response and investigate its potential role in response to immunotherapy in patients (pts) with MSS chemorefractory mCRC.
Researchers enrolled pts with MSS chemo refractory (anti-EGFR refractory if RAS wild-type) mCRC to the study, with 28 pts with RAS wild-type and 27 pts with RAS mutations. These pts were treated with CET and IRI beginning from week 1 (W1) and AVE starting from week 3 (W3). The clinical objectives were to evaluate safety and efficacy.
Peripheral blood mononuclear cells from these pts were characterized for immune populations’ phenotypes (including B, T, natural killer (NK), and myeloid cell populations) and proportions by employing high-dimensional flow cytometry and FlowJo™.
Alterations in immune cell proportions were analyzed over time, with sequential blood samples collected at follwoing intervals- W0, W3, and W11. These manifestations were then correlated with response values, progression-free survival (PFS), and overall survival (OS) in the included pts. Wilcoxon test was used for the P-value calculations.
Of 55 treated pts, 148 blood samples (W0: 55, W3: 53, W11: 40) were available for flow cytometry analyses. Overall, B, T, NK, and myeloid cell populations remained stable over time and were not associated with clinical efficacy. However, some T and NK cell subpopulations showed variations.
Irrespective of RAS mutational status, a decrease in TH17 frequency over time was associated with PFS ≤ 6 months (P=0.0018), OS ≤ 12 months (P=0.0083), and tumor growth (P=1.6e-05). At baseline, a lower frequency of circulating NKT cells was associated with tumor response (P=0.02), and an increase in NKT cell frequency over time was associated with tumor response (P=0.00076), PFS > 6 months (P=0.0086), and OS > 12 months (P=0.0069).
The study concluded that the modifications of TH17 and NKT cell frequencies in MSS mCRC pts’ blood included in the AVETUXIRI trial were thought to have a potential association with tumor response and post-treatment survival.
The trial was sponsored by Cliniques universitaires Saint-Luc- Université Catholique de Louvain.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/3
Clinica Trial: https://www.clinicaltrials.gov/study/NCT03608046
BENIDOVSKAYA E, Huyghe N, Carrasco J, et al (2024). “Avelumab (AVE), cetuximab (CET) and irinotecan (IRI) for treatment refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): Characterization of the circulating immune response in the AVETUXIRI phase II trial.” Presented at ESMO-GI 2024, (Abstract 120P).
