Top Line: Does the addition of immunotherapy improve response rates to standard neoadjuvant therapy for locally advanced rectal cancer?
The Study: Several recent trials have shown encouraging response rates when various immune checkpoint inhibitors are added in the neoadjuvant setting. In this randomized, parallel phase 2 trial, 55 patients with locally advanced rectal cancer (T3N+ or T4) received long course chemoradiation consisting of 45-50.4 Gy in 25-28 fractions with concurrent capecitabine. They were then randomized to receive three cycles of either atezolizumab alone or atezolizumab plus tiragolumab. Tiragolumab is a monoclonal antibody that inhibits TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is an inhibitory immune checkpoint receptor expressed on T cells and NK cells. TIGIT and PD-1 are often coexpressed, so the idea is that dual immune checkpoint inhibition could improve antitumor immune response. In the trial, both arms were compared to an historical control pathologic complete response rate of 15%. The pCR rate with atezo + tira was significantly higher than historical control (35.7% v 15%) whereas the pCR rate with atezo alone was not (22.2% v 15%). The rates of grade 3+ adverse events were 31% with atezo + tira and 26.9% with atezo alone.
TBL: In this small trial, dual immune checkpoint inhibition significantly improved pathologic complete response when added to standard neoadjuvant chemoradiation. | Tang, J Clin Oncol 2025
The Study: Several recent trials have shown encouraging response rates when various immune checkpoint inhibitors are added in the neoadjuvant setting. In this randomized, parallel phase 2 trial, 55 patients with locally advanced rectal cancer (T3N+ or T4) received long course chemoradiation consisting of 45-50.4 Gy in 25-28 fractions with concurrent capecitabine. They were then randomized to receive three cycles of either atezolizumab alone or atezolizumab plus tiragolumab. Tiragolumab is a monoclonal antibody that inhibits TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is an inhibitory immune checkpoint receptor expressed on T cells and NK cells. TIGIT and PD-1 are often coexpressed, so the idea is that dual immune checkpoint inhibition could improve antitumor immune response. In the trial, both arms were compared to an historical control pathologic complete response rate of 15%. The pCR rate with atezo + tira was significantly higher than historical control (35.7% v 15%) whereas the pCR rate with atezo alone was not (22.2% v 15%). The rates of grade 3+ adverse events were 31% with atezo + tira and 26.9% with atezo alone.
TBL: In this small trial, dual immune checkpoint inhibition significantly improved pathologic complete response when added to standard neoadjuvant chemoradiation. | Tang, J Clin Oncol 2025