Can we improve total neoadjuvant therapy for rectal cancer?

Veliparib or pembrolizumab, added to total neoadjuvant therapy (TNT), did not improve short-term outcomes in patients with locally advanced rectal cancer (LARC), the NRG-GI002 trial demonstrated. However, the updated data indicate that pembrolizumab may improve the overall survival of these patients.

“The NRG-GI002 trial (NCT02921256) is designed to seek novel therapeutic options to improve the current TNT in patients with LARC,” said Dr Thomas George (University of Florida, FL, USA). All included patients with very high-risk stage 2 or 3 LARC received 8 cycles of mFOLFOX6 chemotherapy, chemoradiotherapy, and surgery. In the 2 experimental arms, patients were administered to additional veliparib (n=90), during radiotherapy, or pembrolizumab (n=90), starting from the first day of radiotherapy [1]. The primary endpoint was the reduction in the neoadjuvant rectal (NAR) score. Previous results did not reveal a benefit for either one of the experimental arms over the control arm regarding the primary outcome [2,3]. Dr George presented the updated findings.

There was no significant difference between the control arm (mean 12.5) or the veliparib (mean 13.3) arm in terms of the Neoadjuvant Rectal (NAR) score (Log-rank P=0.81) [4] or any of the other short-term or long-term outcomes. Dr George added that there was a trend towards a worse overall survival (OS) in the veliparib group compared with the control group: 3-year OS (85% vs 92%; HR 2.13; 95% CI 0.86–5.29; P=0.10). Patients in the pembrolizumab arm (mean 11.5) did not demonstrate a significant advantage over the control arm (mean 14.4) in terms of NAR score either (Log-rank P=0.21). The 3-year OS rates, however, suggest that pembrolizumab may deliver a benefit for these patients in the long run (95% vs 87%; HR 0.35; 95% CI 0.12–1.00; Log-rank P=0.04).

“Molecular interrogation of tumour and circulating biomarkers is ongoing to identify subgroups that may benefit from these targeted treatments,” mentioned Dr George at the end of his talk.

1. George TJ, et al. Long-term results from NRG-GI002: A phase II clinical trial platform using total neoadjuvant therapy (TNT) in locally advanced rectal cancer (LARC). Abstract 7, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.
2. George TJ, et al. JCO. 2019;37(15suppl):abstr 3505.
3. Rahma OE, et al. JAMA Oncol. 2021;7(8):1225–1230.
4. George Jr TJ, et al. Curr Colorectal Cancer Rep. 2015;11(5):275–280.

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Posted on 17 March, 2023