Clinical trialPhase 3Colorectal cancer

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

N Engl J Med · 2026712 patients (355 atezolizumab + mFOLFOX6, 357 mFOLFOX6 alone)

Sinicrope FA, Ou FS, Arnold D, et al. N Engl J Med. 2026. 394:1155-1166

Study type: Clinical trial
Study name: ATOMIC (Alliance A021502)
Phase: Phase 3
Design: Randomised, open-label, multicentre trial (US NCTN network and the German AIO group), 1:1 randomisation
Sample size: 712 patients (355 atezolizumab + mFOLFOX6, 357 mFOLFOX6 alone)
Source: N Engl J Med · 2026
Trial registration: NCT02912559

In plain words

After surgery for stage 3 colon cancer, about 6 months of chemotherapy (such as FOLFOX) is usually given to lower the risk of the cancer coming back. In patients whose tumour has the dMMR feature, this large study showed that adding the immunotherapy drug atezolizumab to chemotherapy (and continuing it for up to a year) roughly halved the risk of the cancer coming back or death: after 3 years, 86% of patients in the combined group were free of disease, compared with 76% in the chemotherapy-only group. Serious side effects were slightly more common (especially tiredness and low white blood cell counts). This is why testing the tumour for MMR/MSI is very important for everyone with colon cancer.

Key results

86.3% vs 76.2%

3-year disease-free survival

95% CI: 81.8–89.8 vs 70.9–80.6; median follow-up 40.9 months

0.50

Hazard ratio for recurrence or death

95% CI 0.35–0.73; P<0.001

84.1% vs 71.9%

Grade 3 or 4 adverse events

Atezolizumab + mFOLFOX6 versus mFOLFOX6

Drugs in this study:Fluorouracil (5-FU)Oxaliplatin (Eloxatin)Atezolizumab (Tecentriq)

Dose and schedule cards

mFOLFOX6

Stage III colon cancer after surgery; alternative to CAPOXCycle length: Every 14 daysOn the page “Colorectal cancer” · Stage III colon cancer: adjuvant chemotherapy

Stage III colon cancer after surgery; alternative to CAPOX

Drug	Dose	Route	Schedule
Oxaliplatin	85 mg/m²	IV over 2 h	Day 1
Leucovorin	400 mg/m²	IV over 2 h	Day 1
Fluorouracil (bolus)	400 mg/m²	IV bolus	Day 1
Fluorouracil (infusion)	2400 mg/m²	IV, continuous 46-h infusion	Starting day 1

Cycle length: Every 14 days
Duration: 12 cycles (6 months)

Doses from the ATOMIC trial (mFOLFOX6 arm). In IDEA, unlike CAPOX, three months of FOLFOX was not as effective as six months, and longer treatment gave better disease-free survival, particularly in high-risk patients. The regimen in the FDA label is FOLFOX4: oxaliplatin 85 and leucovorin 200 mg/m² over 2 hours, then fluorouracil 400 mg/m² as a bolus and 600 mg/m² as a 22-hour infusion on day 1, and leucovorin and fluorouracil at the same doses on day 2; every 14 days for up to 12 cycles.

Oxaliplatin modifications per the label (adjuvant setting): persistent grade 2 sensory neuropathy → consider reducing to 75 mg/m²; persistent grade 3 → consider discontinuing; grade 4 → discontinue. Grade 4 or febrile neutropenia, or grade 3–4 thrombocytopenia → delay until neutrophils ≥1,500 and platelets ≥75,000/µL, then give oxaliplatin 75 mg/m². Creatinine clearance below 30 mL/min → oxaliplatin 65 mg/m².

On the page “Colorectal cancer” · Stage III colon cancer: adjuvant chemotherapy

Atezolizumab + mFOLFOX6 (ATOMIC)

Stage III colon cancer with DNA mismatch repair deficiency (dMMR), after surgery; in the trial, started within 10 weeks of surgeryCycle length: Every 14 daysOn the page “Colorectal cancer” · Stage III colon cancer: adjuvant chemotherapy

Stage III colon cancer with DNA mismatch repair deficiency (dMMR), after surgery; in the trial, started within 10 weeks of surgery

Drug	Dose	Route	Schedule
Phase 1: 12 cycles (6 months)
Atezolizumab	840 mg	IV (before chemotherapy)	Day 1
Oxaliplatin	85 mg/m²	IV over 2 h	Day 1
Leucovorin	400 mg/m²	IV over 2 h	Day 1
Fluorouracil (bolus)	400 mg/m²	IV bolus	Day 1
Fluorouracil (infusion)	2400 mg/m²	IV, continuous 46-h infusion	Starting day 1
Phase 2: 13 cycles (6 months)
Atezolizumab monotherapy	840 mg	IV	Day 1

Cycle length: Every 14 days
Duration: Atezolizumab for 12 months in total; mFOLFOX6 for 6 months

ATOMIC trial regimen. The FDA label for atezolizumab includes this use: 840 mg every 2 weeks (or 1200 mg every 3 weeks or 1680 mg every 4 weeks) with chemotherapy for 6 months, followed by monotherapy for 6 months; if chemotherapy is stopped early, atezolizumab is continued to a total of 12 months; dose reduction of atezolizumab is not recommended.

On the page “Colorectal cancer” · Stage III colon cancer: adjuvant chemotherapy

Adjuvant atezolizumab + mFOLFOX6 (ATOMIC)

dMMR stage III colon cancer after complete resection; FDA-approvedCycle length: Every 14 daysOn the page “Immunotherapy and organ preservation in dMMR tumours” · Regimens from the key studies

dMMR stage III colon cancer after complete resection; FDA-approved

Drug	Dose	Route	Schedule
First 6 months
Atezolizumab	840 mg (or 1200 every 3 weeks or 1680 every 4 weeks)	IV infusion over 60 minutes, then over 30 minutes if tolerated; before chemotherapy	Every 2 weeks
First 6 months (12 cycles)
mFOLFOX6: oxaliplatin + leucovorin	85 mg/m² + 400 mg/m²	IV	Day 1
Fluorouracil	400 mg/m² bolus, then 2400 mg/m²	Bolus, then continuous infusion over 46 hours	Days 1 to 3
Second 6 months
Single-agent atezolizumab	840 mg	IV	Every 2 weeks (13 cycles)

Cycle length: Every 14 days
Duration: 12 months of atezolizumab in total (if chemotherapy stops early, atezolizumab continues to 12 months)

Doses from the atezolizumab FDA label. Dose reduction of atezolizumab is not recommended; immune-related adverse events are managed by holding or stopping and corticosteroids.

On the page “Immunotherapy and organ preservation in dMMR tumours” · Regimens from the key studies

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Atezolizumab + mFOLFOX6

Atezolizumab 840 mg IV every 2 weeks with mFOLFOX6 for 12 cycles (6 months), then atezolizumab monotherapy for 13 further cycles (12 months of treatment in total).

mFOLFOX6 every 14 days: oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil (5-FU) 400 mg/m² bolus followed by 2400 mg/m² continuous infusion over 46 hours.

2mFOLFOX6 alone (control arm)

mFOLFOX6 at the same doses (oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil 400 mg/m² bolus and 2400 mg/m² over 46 hours) every 2 weeks for 12 cycles (6 months).

Source of the regimen details: Full text of the paper in PMC (PMC13020640): atezolizumab 840 mg IV every 2 weeks for 12 cycles with mFOLFOX6 followed by 13 cycles as monotherapy; mFOLFOX6 doses from the same source; ClinicalTrials.gov NCT02912559

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with resected stage 3 mismatch repair-deficient (dMMR) colon cancer (randomised up to 10 weeks after surgery). Median age 64 years, 55.1% women, and 53.9% with high-risk tumours (T4, N2 or both).

Endpoints

Primary endpoint: disease-free survival (DFS).

Secondary endpoints: overall survival and adverse event profile.

Safety and side effects

Grade 3 or 4 adverse events (regardless of attribution) occurred in 84.1% of the atezolizumab + mFOLFOX6 group and 71.9% of the mFOLFOX6 group; grade 3 or 4 non-haematological events: 69.4% versus 54.5%, including fatigue 10.1% versus 3.3%. Immune-related adverse events of any grade (hypothyroidism, hyperglycaemia, colitis and rash) were more frequent in the atezolizumab group, but the rates of grade 3 and 4 events were similar in the two groups.

Clinical significance and place in guidelines

ATOMIC was the first phase 3 trial to show a benefit of adjuvant immunotherapy in colon cancer. On the basis of this study, on 8 October 2026 the FDA approved atezolizumab with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adults and children aged 2 years and older with stage 3 mismatch repair-deficient (dMMR) colon cancer; the subcutaneous form (atezolizumab and hyaluronidase) was also approved for patients aged 12 years and older weighing at least 40 kg.

Limitations

The trial was open-label (no placebo). Overall survival data were not yet mature at publication. Benefit was examined only in stage 3 dMMR tumours and cannot be extrapolated to pMMR or stage II colon cancers. The study also did not compare a preoperative immunotherapy approach (such as NICHE-2) with adjuvant treatment.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.