FDA Approves Atezolizumab Plus Chemo for Stage 3 dMMR Colon Cancer

The FDA has approved atezolizumab (Tecentriq) in combination with a fluoropyrimidine and oxaliplatin for the adjuvant treatment of adult and pediatric patients 2 years and older with stage 3 mismatch repair–deficient (dMMR) colon cancer. The agency also approved the subcutaneous formulation, atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza), with the same chemotherapy backbone for patients 12 years and older who weigh at least 40 kg.

The October 8, 2026, decision is based on the phase 3 ATOMIC trial (Alliance A021502; NCT02912559), in which adding the PD-L1 inhibitor to modified FOLFOX6 (mFOLFOX6) reduced the risk of disease recurrence or death by 50% compared with mFOLFOX6 alone (HR, 0.50; 95% CI, 0.35-0.73). The gain came with a higher rate of grade 3 to 4 adverse events, driven largely by neutropenia, and overall survival data were not mature at the time of publication in The New England Journal of Medicine.

What did the ATOMIC trial study?

ATOMIC was a multicenter, randomized, open-label, active-controlled trial that enrolled 711 adults and 1 pediatric patient with stage 3 dMMR colon cancer after complete resection of the primary tumor, with no evidence of residual lymph node involvement or metastatic disease. Patients were enrolled at 303 National Clinical Trials Network sites and 9 Arbeitsgemeinschaft Internistische Onkologie (AIO) sites in Germany between September 2017 and January 2023. Mismatch repair status was determined by immunohistochemistry, for example with the VENTANA MMR RxDx Panel. More than half of patients (53.9%) had high-risk tumors, defined as T4, N2, or both.

Patients were randomly assigned 1:1 to receive atezolizumab plus mFOLFOX6 (oxaliplatin, leucovorin, and fluorouracil) for 12 cycles followed by atezolizumab monotherapy for 6 months, or mFOLFOX6 alone for 12 cycles. The primary end point was investigator-assessed disease-free survival (DFS); secondary end points included overall survival (OS) and adverse events.

How much did atezolizumab improve disease-free survival?

At a median follow-up of 40.9 months, the published results showed:

• 3-year DFS: 86.3% (95% CI, 81.8%-89.8%) with atezolizumab plus mFOLFOX6 vs 76.2% (95% CI, 70.9%-80.6%) with mFOLFOX6 alone
• DFS hazard ratio: 0.50 (95% CI, 0.35-0.73; P < .001)
• Median DFS: not reached in either arm

The FDA reported a P value of .0001 for the DFS comparison. In an exploratory analysis, the hazard ratio was 0.41 (95% CI, 0.27-0.64) among patients who received more than 6 cycles of mFOLFOX6 and 0.97 (95% CI, 0.44-2.11) among those who received 6 or fewer cycles.

What toxicity differences should nurses know about?

Grade 3 to 4 adverse events occurred in 84.1% of patients receiving atezolizumab plus mFOLFOX6 vs 71.9% of those receiving mFOLFOX6 alone. The most common grade 3 to 4 events were:

• Decreased neutrophil count: 43.6% vs 35.9%
• Peripheral sensory neuropathy: 18.5% vs 15.0%
• Fatigue: 10.1% in the atezolizumab arm
• Hypertension: 11.7% in the control arm

Two deaths in the atezolizumab arm were considered treatment related, 1 from sudden death and 1 from sepsis. The prescribing information carries warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

What is the recommended dosing?

For adults, intravenous atezolizumab is given at 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks with chemotherapy for 6 months, followed by single-agent atezolizumab for 6 months or until disease recurrence or unacceptable toxicity. Pediatric patients receive 10 mg/kg (maximum 840 mg) every 2 weeks or 15 mg/kg (maximum 1200 mg) every 3 weeks on the same schedule.

The subcutaneous formulation is given as one 15-mL injection every 3 weeks, containing 1875 mg of atezolizumab and 30,000 units of hyaluronidase, with chemotherapy for 6 months and then as monotherapy for 6 months or until recurrence or unacceptable toxicity. Dosing has not been established for patients younger than 12 years or for those 12 years and older who weigh less than 40 kg.

What did investigators and advocates say about the results?

When the data were first presented at the 2025 American Society of Clinical Oncology Annual Meeting, lead author Frank A. Sinicrope, MD, coleader of the Gastrointestinal Cancer Program and clinical investigator at the Mayo Foundation in Rochester, Minnesota, described the findings during a press briefing.

"These data establish this combination as a new standard treatment for patients with stage III colon cancer and dMMR," Sinicrope said.

He added that the benefit held across subgroups: "No matter the patient's age, their sex, their race, their location, T-stage, or N-stage, patients are doing better with the addition of immunotherapy to chemotherapy."

Joel Saltzman, MD, a medical oncologist at Taussig Cancer Center, Cleveland Clinic, in Ohio, pointed to the trial's applicability during the briefing. "The most important thing about this study is that it involves a real-world population that I will see in my clinic," he said.

Ahead of the FDA decision, Michael Sapienza, chief executive officer of the Colorectal Cancer Alliance, said, "One in three patients with stage 3 colon cancer will relapse within five years, underscoring the need for new adjuvant treatment options."

How does this approval fit into colon cancer care?

Standard adjuvant therapy for stage 3 colon cancer has consisted of a fluoropyrimidine plus oxaliplatin. Approximately 15% of colon cancers are dMMR or microsatellite instability–high, a subset with high mutation rates that may respond to immunotherapy. At the 2025 presentation, which Oncology Nursing News covered, Sinicrope described ATOMIC as the first adjuvant immunotherapy study in colon cancer.

The trial was open label, and DFS was investigator assessed. OS data remain immature, and the exploratory analysis by number of chemotherapy cycles was not powered to guide treatment decisions. The study was funded by the National Cancer Institute and Genentech.

The FDA reviewed the application under Project Orbis with regulators in Australia, Canada, Israel, and Switzerland, whose reviews are ongoing, and granted it priority review.

What are the key takeaways for oncology nurses?

• Confirm MMR status: Eligibility depends on dMMR status from tumor testing, so verify that results are documented before adjuvant therapy is planned.
• Prepare patients for a 12-month course: Atezolizumab continues for 6 months after chemotherapy ends, which extends visits and monitoring beyond the standard 6-month FOLFOX course.
• Monitor counts closely: Grade 3 to 4 neutrophil decreases occurred in 43.6% of patients receiving the combination vs 35.9% with chemotherapy alone.
• Watch for immune-mediated adverse reactions: Teach patients to report new diarrhea, cough, shortness of breath, rash, jaundice, or unusual fatigue, including during the monotherapy phase and after treatment ends.
• Track neuropathy: Grade 3 to 4 peripheral sensory neuropathy occurred in 18.5% of patients receiving the combination and 15.0% of those receiving chemotherapy alone.
• Discuss route options: The subcutaneous formulation, given every 3 weeks to eligible patients 12 years and older who weigh at least 40 kg, may shorten chair time.
• Support shared decision-making: Patients can weigh a 50% reduction in risk of recurrence or death against higher grade 3 to 4 toxicity and OS data that are not yet mature.

References

1. FDA approves atezolizumab in combination with chemotherapy for stage III mismatch repair deficient colon cancer. News release. US Food and Drug Administration. October 8, 2026. Accessed October 8, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-atezolizumab-combination-chemotherapy-stage-iii-mismatch-repair-deficient-colon-cancer
2. Sinicrope FA, Ou FS, Arnold D, et al. Atezolizumab plus FOLFOX for stage III mismatch repair-deficient colon cancer. N Engl J Med. 2026;394(12):1155-1166. doi:10.1056/NEJMoa2507874
3. FDA grants priority review for Genentech's Tecentriq for a certain type of stage III colon cancer. News release. Genentech. June 10, 2026. Accessed October 8, 2026. https://www.gene.com/media/press-releases/15116/2026-06-10/fda-grants-priority-review-for-genentech
4. Sinicrope FA, Ou F-S, Arnold D, et al. Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502; ATOMIC). J Clin Oncol. 2025;43(suppl 17):LBA1. doi:10.1200/JCO.2025.43.17_suppl.LBA1
5. Berberabe T. Atezolizumab plus chemo boosts DFS in stage III dMMR colon cancer. Oncology Nursing News. June 1, 2025. Accessed October 8, 2026. https://www.oncnursingnews.com/view/atezolizumab-plus-chemo-boosts-dfs-in-stage-iii-dmmr-colon-cancer
6. Testing the addition of atezolizumab to adjuvant chemotherapy in stage III colon cancer (ATOMIC). ClinicalTrials.gov identifier: NCT02912559. Updated [verify date]. Accessed October 8, 2026. https://clinicaltrials.gov/study/NCT02912559