Details

Autor(en) / Beteiligte

• Marolleau, Pauline
• Tougeron, David
• Allignet, Benoit
• Cohen, Romain
• Sefrioui, David
• Gallet, Blandine
• Dumont, Frédéric
• Guimbaud, Rosine
• Alouani, Emily
• Passot, Guillaume
• Desolneux, Grégoire
• Ghiringhelli, François
• Marchal, Frédéric
• Mourthadhoi, Farouk
• Coriat, Romain
• Desgrippes, Romain
• Locher, Christophe
• Goujon, Gaël
• Des Guetz, Gaëtan
• Aparicio, Thomas
• Paubelle, Etienne
• Dupré, Aurélien
• Fouchardière, Christelle

Titel

Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study

Ist Teil von

• International journal of cancer, 2023-10, Vol.153 (7), p.1376-1385

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2023

Quelle

Wiley Online Library

Beschreibungen/Notizen

• About 5% of the patients with metastatic colorectal cancers (mCRC) present microsatellite instability (MSI)/deficient mismatch repair system (dMMR). While metastasectomy is known to improve overall and progression‐free survival in mCRC, specific results in selected patients with dMMR/MSI mCRC are lacking. Our study aimed to describe metastasectomy results, characterize histological response and evaluate pathological complete response (pCR) rate in patients with dMMR/MSI mCRC. We retrospectively reviewed data from all consecutive patients with dMMR/MSI mCRC who underwent surgical metastasectomy between January 2010 and June 2021 in 17 French centers. Primary outcome was to assess the pCR rate defined by tumor regression grade (TRG) 0. Secondary endpoints included relapse‐free survival (RFS) and overall survival (OS), and explored TRG as predictive factor for RFS and OS. Among the 88 patients operated, 109 metastasectomies were performed in 81 patients after neoadjuvant treatment [chemotherapy ± targeted therapy (CTT): 69, 85.2%; immunotherapy (ICI): 12, 14.8%], and pCR was achieved in 13 (16.1%) patients. Among the latter, pCR rate were 10.2% in the patients having received CTT (N = 7) and 50.0% in the patients treated with ICI (N = 6). Radiological response did not predict TRG. With a median follow‐up of 57.9 (IQR 34.2‐81.6) months, median RFS was 20.2 (15.4‐not reached) months, median OS was not reached. Major pathological responses (TRG0 + TRG1) were significantly associated with longer RFS (HR 0.12, 95% CI 0.03‐0.55; P = .006). The pCR rate of 16.1% achieved with neoadjuvant treatment in patients with dMMR/MSI mCRC is consistent with previously reported rates in pMMR/MSS mCRC. Immunotherapy showed better pCR rate than chemotherapy ± targeted therapy. Further prospective trials are needed to validate immunotherapy as neoadjuvant treatment in resectable/potentially resectable dMMR/MSI mCRC and identify predictive factors for pCR. What's new? Pathological responses to neoadjuvant treatment have been shown to predict survival outcome after surgery in metastatic colorectal cancer. However, most of the current data were collected before the approval of immune checkpoint inhibitors as standard treatment for metastatic colorectal cancer in Europe and the use of MMR/MSI status as predictive response factor. This retrospective multicenter study in dMMR/MSI metastatic colorectal cancer patients who underwent metastasectomy shows a pathological complete response rate of 16.1% to neoadjuvant treatment, comparable to that in pMMR/MSS metastatic colorectal cancer patients. Immunotherapy showed a better pathological complete response rate than chemotherapy with or without targeted therapy.