Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer

Author(s): Frank A. Sinicrope, M.D.1,2; Fang-Shu Ou, Ph.D.3; Dirk Arnold, M.D.4; Walter R. Peters, M.D.5; Robert J. Behrens, M.D.6; Christopher H. Lieu, M.D.7; Khalid Matin, M.D.8; Deirdre J. Cohen, M.D.9; Samara L. Potter, M.D.10; Andrew B. Nixon, Ph.D.11; Lisa A Kottschade, A.P.R.N., C.N.P.1; Emily Kathol, Pharm.D.12; Wendy L. Frankel, M.D.13; Ardaman Shergill, M.D.14,15; Dennis Hsu, M.D.16; Anke Reinacher-Schick, M.D.17; Paul Mehan, M.D.18; Philip J. Gold, M.D.19; Maged F. Khalil, M.D.20; Tyler Zemla, M.S.3; Clare Gatten, M.A.3; Eileen M. O’Reilly, M.D.21; Jeffrey A. Meyerhardt, M.D.22;
Source: DOI: 10.1056/NEJMoa2507874
Original Article
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Dr. Anjan Patel's Thoughts

This is a strong adjuvant signal in resected stage III dMMR colon cancer, adding atezolizumab to mFOLFOX6 cut the risk of recurrence or death in half and improved 3-year DFS from 76% to 86%. OS hasn’t separated yet, but that may be confounded by immunotherapy at relapse. Toxicity was higher, as expected, with more grade 3–4 events and immune-related adverse events (AE)s, but overall manageable. This feels practice changing for stage III dMMR disease.

BACKGROUND

Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti–programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve outcomes in patients with stage III colon cancer with mismatch repair–deficient (dMMR) status is unclear.

METHODS

In a phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with resected stage III dMMR tumors to receive either adjuvant atezolizumab plus mFOLFOX6 for 6 months, with atezolizumab continued as monotherapy (for a total of 12 months of therapy), or mFOLFOX6 alone for 6 months. The primary end point was disease-free survival. Secondary end points were overall survival and the adverse-event profile. Research Summary Atezolizumab plus FOLFOX for Stage III dMMR Colon Cancer

RESULTS

A total of 355 patients were assigned to receive atezolizumab plus mFOLFOX6 and 357 to receive mFOLFOX6 alone. The median age of the patients was 64 years, 55.1% were women, and 53.9% had tumors that were T4, N2, or both (indicating high risk). a median follow-up of 40.9 months, the 3-year disease-free survival was 86.3% (95% confidence interval [CI], 81.8 to 89.8) in the atezolizumab–mFOLFOX6 group, as compared with 76.2% (95% CI, 70.9 to 80.6) in the mFOLFOX6 group (hazard ratio for disease recurrence or death, 0.50; 95% CI, 0.35 to 0.73; P

CONCLUSIONS

The addition of atezolizumab to mFOLFOX6 significantly improved disease-free survival among patients with stage III dMMR colon cancer. (Funded by the National Cancer Institute of the National Institutes of Health and Genentech; ATOMIC ClinicalTrials.gov number, NCT02912559.)

Author Affiliations

1Department of Oncology, Mayo Clinic, Rochester, MN; 2Gastrointestinal Research Unit, Mayo Clinic, Rochester, MN; 3Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN; 4Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona, Hamburg, Germany; 5Baylor University Medical Center, Dallas; 6Iowa-Wide Oncology Research Coalition National Cancer Institute Community Oncology Research Program, Des Moines; 7Division of Medical Oncology, University of Colorado Cancer Center, Aurora; 8Division of Hematology and Oncology, Virginia Commonwealth University, Richmond; 9Tisch Cancer Institute, Icahn School of Medicine Mount Sinai, New York; 10Nationwide Children’s Hospital, Columbus, OH; 11Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, NC; 12Nebraska Medicine, Omaha; 13Department of Pathology, Ohio State University Wexner Medical Center, Columbus; 14Alliance for Clinical Trials in Oncology, Chicago; 15Section of Hematology and Oncology, University of Chicago, Chicago; 16Department of Medicine, Division of Hematology–Oncology, University of Pittsburgh Medical Center, Pittsburgh; 17Department of Hematology and Oncology with Palliative Care, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany; 18Missouri Baptist Medical Center, St. Louis; 19Swedish Medical Center–First Hill, Seattle; 20Lehigh Valley Hospital–Cedar Crest, Allentown, PA; 21Department of Medicine, Memorial Sloan Kettering Cancer Center, New York; 22Department of Medical Oncology, Dana–Farber Cancer Institute, Harvard Medical School, Harvard University, Boston

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