Table 3.
Neoadjuvant immunotherapy.
| Trials | Patients (n) | Patients and Methods | Results | Conclusion | Ref | |
|---|---|---|---|---|---|---|
| RT | Chemotherapy and Immunotherapy | |||||
| VOLTAGE-A | A1(MSS) = 37 | 50.4 Gy | Capecitabine + nivolumab | A1: pCR: 30% (11/37) mpR: 38% (14/37) |
Promising pCR rates of 30% and 60%, with mild toxicities, were shown in MSS and MSI-H LARC patients treated with Nivolumab plus radical surgery after CRT, suggesting the candidate therapy for the future non-surgical approach. | [51] |
| A2(MSI-H) = 5 | A2: pCR: 60% (3/5) mpR: 60% (3/5) |
|||||
| ANAVA | 101 | 50.4 Gy | Capecitabine + avelumab | pCR: 23% (22/96) | The combination of preop CRT plus avelumab showed promising activity and a feasible safety profile. | [52] |
| grade 3–4 non-immune adverse events: 8% | ||||||
| grade 3–4 immune-related adverse events: 4% | ||||||
| NRG-GI002 | Con = 95 | 50.4 Gy | Con: FOLFOX + capecitabine Exp: FOLFOX + capecitabine + pembrolizumab |
Mean NAR: con vs. exp =14.08 vs. 11.53 p = 0.26 |
Pembrolizumab added to CRT as part of TNT was safe and without unexpected short-term toxicities but failed to improve the NAR score. | [53] |
| pCR: 29.4% vs. 31.9%, p = 0.75 | ||||||
| Exp = 90 | cCR: 13.6% vs. 13.9%, p = 0.95 | |||||
| SSS: 71.0% vs. 59.4%, p = 0.15 | ||||||
| NCT04231552 | 30 | 25 Gy | Oxaliplatin + capecitabine + camrelizumab | pCR: 48.1% (13/27) | SC-RT combined with subsequent CAPOX plus camrelizumab followed by delayed surgery showed a favorable pCR rate with good tolerance in patients with LARC, especially in the proficient MMR setting. | [54] |
| pMMR/MSS: 46% (12/26) | ||||||
| dMMR/MSI-H: 100% (1/1) | ||||||
| Averectal | 44 | 25 Gy | mFOLFOX6 + avelumab | pCR: 37.5% (15/40) mpR: 67.5% (27/40) |
The primary endpoint was successfully met with significant improvement in pCR and mpR rates in the setting of an acceptable safety profile. | [55] |
cCR = clinical complete response; Con = Control; CRT = chemoradiotherapy; Exp = Experimental; Gy = Gray; LARC = locally advanced rectal carcinoma; MMR = mismatch repair; mpR = major pathological response; NAR = neoadjuvant rectal cancer; pCR = pathological complete response; SC-RT = short course radiotherapy; SSS = sphincter-sparing surgery; TNT = total neoadjuvant therapy; A1 = cohort A-1; A2 = cohort A-2; MSS = microsatellite stability; MSI-H = high instability microsatellite.