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

Pauline Marolleau (1) , David Tougeron (2) , Benoît Allignet (1) , Romain Cohen (3, 4) , David Sefrioui (5, 6) , Blandine Gallet (7) , Frédéric Dumont (8) , Rosine Guimbaud (9) , Emily Alouani (10) , Guillaume Passot (11) , Grégoire Desolneux (12) , François Ghiringhelli (13) , Frédéric Marchal (14) , Farouk Mourthadhoi (15, 16) , Romain Coriat (17, 18) , Romain Desgrippes (19) , Christophe Locher (20) , Gaël Goujon (21) , Gaëtan Des Guetz (21) , Thomas Aparicio (22) , Etienne Paubelle (23) , Aurélien Dupré (1) , Christelle De La Fouchardière (1, 24)

1 Centre Léon Bérard [Lyon]
2 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
3 CRSA - Centre de Recherche Saint-Antoine
4 CHU Saint-Antoine [AP-HP]
5 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
6 CHU Rouen
7 ICM - UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle
8 UNICANCER/ICO - Institut de Cancérologie de l'Ouest [Angers/Nantes]
9 Département Oncologie médicale digestive [CHU Toulouse]
10 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
11 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
12 Institut Bergonié [Bordeaux]
13 UNICANCER/CRLCC-CGFL - Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon]
14 UNICANCER/ICL - Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
15 UJM - Université Jean Monnet - Saint-Étienne
16 CHU ST-E - Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne]
17 UPD5 - Université Paris Descartes - Paris 5
18 Hôpital Cochin [AP-HP]
19 CH de Saint-Malo [Broussais]
20 Centre Hospitalier de Meaux
21 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
22 AP-HP - Hopital Saint-Louis [AP-HP]
23 CHU Amiens-Picardie
24 IPC - Institut Paoli-Calmettes

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.

Mots clés: deficient mismatch repair system; metastatic colorectal cancer; microsatellite instability; pathological complete response; immune checkpoint inhibitors; neoadjuvant treatment

Domaines: Cancer; Immunothérapie; Hépatologie et Gastroentérologie; Pharmacologie; Santé publique et épidémiologie

Pauline Marolleau, David Tougeron, Benoît Allignet, Romain Cohen, David Sefrioui, et al.. Complete pathological response after chemotherapy or immune checkpoint inhibitors in deficient MMR metastatic colorectal cancer: Results of a retrospective multicenter study. International Journal of Cancer, inPress, ⟨10.1002/ijc.34636⟩. ⟨hal-04155601⟩