Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial
People prefer stool card over colonoscopy, and it is not inferior.
Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair–Deficient Colon Cancer
Author(s): Myriam Chalabi, M.D., Ph.D. https://orcid.org/0000-0002-8607-6174, Yara L. Verschoor, M.D. https://orcid.org/0009-0005-7217-1460, Pedro Batista Tan, M.Sc., Sara Balduzzi, Ph.D., Anja U. Van Lent, M.D., Ph.D., Cecile Grootscholten, M.D., Ph.D., Simone Dokter, M.Sc., Nikè V. Büller, M.D., Ph.D., Brechtje A. Grotenhuis, M.D., Ph.D., Koert Kuhlmann, M.D., Ph.D., Jacobus W. Burger, M.D., Ph.D., Inge L. Huibregtse, M.D., Ph.D., Tjeerd S. Aukema, M.D., Ph.D., Eduard R. Hendriks, M.D., Steven J. Oosterling, M.D., Ph.D., Petur Snaebjornsson, M.D., Ph.D., Emile E. Voest, M.D., Ph.D., Lodewyk F. Wessels, Ph.D., Regina G. Beets-Tan, M.D., Ph.D., Monique E. Van Leerdam, M.D., Ph.D., Ton N. Schumacher, Ph.D., José G. van den Berg, M.D., Ph.D., Geerard L. Beets, M.D., Ph.D., and John B. Haanen, M.D., Ph.D.
Source: N Engl J Med 2024;390:1949-1958
Dr. Maen Hussein's Thoughts
Epi and nivo for mismatch repair-deficient (dMMR) colon cancer had 98% response rate with 68% complete response, non-recurred with a median of follow up of 26 months. Does this mean bye-bye surgery??? Probably. We will need to assess those who have complete response and have a close follow up. CtDNA may play big role here, along with a need for randomized trials.
BACKGROUND
Mismatch repair–deficient (dMMR) tumors can be found in 10 to 15% of patients with nonmetastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited.METHODS
We conducted a phase 2 study in which patients with nonmetastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab. The two primary end points were safety, defined by timely surgery (i.e., ≤2-week delay of planned surgery owing to treatment-related toxic events), and 3-year disease-free survival. Secondary end points included pathological response and results of genomic analyses.RESULTS
Of 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93 to 100) underwent timely surgery; 2 patients had surgery delayed by more than 2 weeks. Grade 3 or 4 immune-related adverse events occurred in 5 patients (4%), and none of the patients discontinued treatment because of adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94 to 100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumor) and 75 (68%) with a pathological complete response (0% residual viable tumor). With a median follow-up of 26 months (range, 9 to 65), no patients have had recurrence of disease.CONCLUSIONS
In patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients. (Funded by Bristol Myers Squibb; NICHE-2 ClinicalTrials.gov number, NCT03026140.)Author Affiliations
From the Departments of Gastrointestinal Oncology (M.C., Y.L.V., P.B.T., C.G., S.D., N.V.B., I.L.H., M.E.V.L.), Medical Oncology (M.C., C.G., N.V.B., E.E.V., J.B.H.), Biometrics (S.B.), Surgery (B.A.G., K.K., G.L.B.), Pathology (P.S., J.G.B.), Molecular Oncology and Immunology (E.E.V., T.N.S.), and Radiology (R.G.B.-T.), and the Division of Molecular Carcinogenesis (L.F.W.), Netherlands Cancer Institute, and the Department of Gastroenterology and Hepatology, OLVG Hospital (A.U.V.L.), Amsterdam, the Department of Surgery, Catharina Hospital Eindhoven, Eindhoven (J.W.B.), the Department of Surgery, Haga Hospital, the Hague (T.S.A.), the Department of Surgery, Tergooi MC, Hilversum (E.R.H.), the Department of Surgery, Spaarne Gasthuis, Haarlem (S.J.O.), Oncode Institute, Utrecht (E.E.V., L.F.W., T.N.S.), the Faculty of EEMCS, Delft University of Technology, Delft (L.F.W.), GROW School for Oncology and Reproduction, Maastricht University, Maastricht (R.G.B.-T., G.L.B.), and the Departments of Gastroenterology and Hepatology (M.E.V.L.), Hematology (T.N.S.), and Medical Oncology (J.B.H.), Leiden University Medical Center, Leiden — all in the Netherlands; the Faculty of Medicine, University of Iceland, Reykjavik (P.S.); and the Melanoma Clinic, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland (J.B.H.).Related Articles
Assessment of the Addition of Oxaliplatin to Fluoropyrimidine-Based Adjuvant Chemotherapy in Patients With High-Risk Stage II Colon Cancer: An ACCENT Pooled Analysis
No oxaliplatinum in stage 2 colon cancer, even high-risk patients, by the way, De Gramont is one of the authors (father of FOLOFX reigmens).
Oxaliplatin-Based Adjuvant Chemotherapy in Older Patients With Stage III Colon Cancer: An ACCENT/IDEA Pooled Analysis of 12 Trials
There is more movement towards using time to relapse as an endpoint for adjuvant studies. This report highlights that there is still a role for oxaliplatin in older patients with Stage III CRC. The time to relapse was not significantly different in patients who are younger vs older. TTR is suggested as a more informative endpoint as older patients uniformly have a lower DFS and OS in most trials.
Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer
COLOXIS is an interesting computer-based learning model that seems to be able to predict which patients are likely to benefit from adjuvant chemotherapy in colorectal cancer. This, along with ctDNA tests, may change whom we choose to offer adjuvant chemotherapy.
Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial
Negative study for the use of HIPEC in the adjuvant setting of high-risk or locally advanced colorectal cancers, including those with perforation and peritoneal invasion. HIPEC doesn’t seem to reduce the risk of peritoneal recurrence after potentially curative resection.