Neoadjuvant immunotherapy in primary and metastatic colorectal cancer

Abstract

Background Colorectal cancer (CRC) is the second most common solid organ cancer. Traditional treatment is with surgery and chemotherapy. Immunotherapy has recently emerged as a neoadjuvant therapy that could change treatment strategy in both primary resectable and metastatic CRC. Methods A literature review of PubMed with a focus on studies exploring upfront immunotherapy in operable CRC, either for primary resectable stage I–III cancers or for (potentially) operable liver metastasis. Results Immune checkpoint blockade by the programmed cell death 1 (PD-1) receptor inhibitors nivolumab and pembrolizumab and the cytotoxic T cell-associated protein 4 (CTLA-4) inhibitor ipilimumab has shown good results in both early-stage and advanced CRC. The effects of immune checkpoint inhibitors have so far been demonstrated in small phase I/II studies and predominantly in treatment-refractory stage IV disease with defect Mismatch repair (dMMR). However, recent data from phase I/II (NICHE-1) studies suggest an upfront role for immunotherapy in operable stage I–III disease. By blocking crucial immune checkpoints, cytotoxic T cells are activated and release cytotoxic signals that initiate cancer cell destruction. The very high complete response rate in dMMR operable CRC with neoadjuvant immunotherapy with nivolumab and ipilimumab, and even partial pathological response in some patients with proficient MMR (pMMR) CRC, calls for further attention to patient selection for neoadjuvant treatment, beyond MMR status alone. Conclusion Early data on the effect of immunotherapy in CRC provide new strategic thinking of treatment options in CRC for both early-stage and advanced disease, with prospects for new trials.

The Safety and Efficacy of Neoadjuvant Camrelizumab Plus Chemotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma: A Retrospective Study

“…8,9 Neoadjuvant anti-PD-1 agents prior to surgery have demonstrated encouraging efficacy with favorable tolerability in several cancers including lung cancer, melanoma and colorectal cancer. [10][11][12] Moreover, anti-PD-1 agents combined with chemotherapy or chemoradiation was recently explored for neoadjuvant therapy in locally advanced ESCC, which exhibited an acceptable therapeutic response and a low-toxicity profile. [13][14][15][16] Park et al reported that neoadjuvant pembrolizumab plus platinum-based chemoradiotherapy may not increase the operative risk or reduce the quality of radical dissection including lymphadenectomy.…”

Neoadjuvant chemoradiotherapy with camrelizumab in patients with locally advanced esophageal squamous cell carcinoma

“…Recently, anti-programmed death 1 (PD-1) antibodies have paved the way for a new era of cancer immunotherapy, and thus have been approved by the Food and Drug Administration as second-line treatment in unresectable ESCC patients (7,8). Neoadjuvant administration of anti-PD-1 agents has demonstrated encouraging efficacy with favorable tolerability in other malignancies including lung cancer, melanoma and colorectal cancer (9)(10)(11). Moreover, anti-PD-1 agents combined with chemotherapy or chemoradiation has been exploited in a neoadjuvant treatment setting for locally advanced ESCC, the results of which produced an acceptable therapeutic response and a low-toxicity profile (12)(13)(14)(15).…”

Parenchymsparende Operationen oder anatomische Resektionen bei Lebermetastasen des kolorektalen Karzinoms?

“…B. Metastasenanzahl) gelten heute nicht mehr, vielmehr ist heute die Frage nach der technischen Resektabilität und der Tumorbiologie entscheidend für die Behandlungsstrategie [34]. Antikörper und Immuncheckpoint-Inhibitoren ergänzen die verfügbaren Chemotherapieprotokolle und können eine Konversion zur Resektabilität erreichen [35]. Allerdings treten Rezidive zumeist intrahepatisch sehr häufig auf [36] diese sind aber durch additive und sich ergänzende Therapien wie Re-Resektion, Chemotherapie oder lokale interventionelle Verfahren durchaus kontrollierbar.…”