FDA Grants Priority Review to Adjuvant Atezolizumab for dMMR Colon Cancer

The FDA has granted priority review to a supplemental biologics license (sBLA) application for atezolizumab and atezolizumab/hyaluronidase-tqjs (Tecentriq Hybreza) for use in combination with modified FOLFOX6 (mFOLFOX6) chemotherapy for the adjuvant treatment of patients with resected stage III mismatch repair-deficient (dMMR) or microsatellite instability–high colon cancer.¹

The sBLA is supported by results from the phase 3 ATOMIC trial (NCT02912559) in which, at a median follow-up of 40.9 months, the 3-year DFS rate was 86.3% (95% CI, 81.8-89.8) in patients receiving atezolizumab plus mFOLFOX6 (n = 355) compared with 76.2% (95% CI, 70.9-80.6) in those receiving mFOLFOX6 alone (n = 357), translating to a 50% reduction in the risk of disease recurrence or death (HR, 0.50; 95% CI, 0.35-0.73; P < .001).^1,2

The benefit was consistent across key subgroups including node stage, tumor stage, and tumor location, and was confirmed in a post hoc per-protocol analysis of 600 patients as well as a separate analysis restricted to the 630 patients with centrally confirmed dMMR status.

In a prespecified subgroup analysis stratified by duration of mFOLFOX6 received, patients who completed more than 6 cycles of chemotherapy demonstrated a notably stronger DFS benefit with atezolizumab (HR, 0.41; 95% CI, 0.27-0.64), whereas those receiving 6 cycles or fewer did not show an advantage (HR, 0.97; 95% CI, 0.44-2.11). These exploratory findings suggest that adequate chemotherapy exposure may be necessary for the atezolizumab benefit to manifest, though this does not constitute definitive evidence.

Overall survival (OS) data were not yet mature at the time of analysis. At a median OS follow-up of 45.8 months, 31 deaths had occurred in the atezolizumab arm and 33 in the chemotherapy arm, with 5-year OS rates of 89.7% (95% CI, 85.2-92.9) and 87.9% (95% CI, 83.1-91.4), respectively (HR, 0.90; 95% CI, 0.55-1.47; P = .68). The investigators noted that interpretation of future OS differences may be complicated by the fact that most patients (84%) in the chemotherapy arm who experienced recurrence subsequently received immunotherapy.

"This filing acceptance brings us closer to establishing adjuvant Tecentriq plus chemotherapy as a new standard of care for certain types of early colon cancer," Levi Garraway, MD, PhD, Roche's chief medical officer and head of Global Product Development, stated in a news release.¹ "The ATOMIC results demonstrate that [atezolizumab] plus chemotherapy can substantially reduce the risk of disease recurrence or death, helping more patients remain cancer-free following surgery."

Safety Profile of Atezolizumab Plus mFOLFOX6

The safety profile of atezolizumab plus mFOLFOX6 was generally consistent with the known profiles of the individual agents, though the combination was associated with a higher rate of grade 3 or 4 adverse events than chemotherapy alone. Grade 3 or 4 events occurred in 84.1% of patients in the atezolizumab arm vs 71.9% in the mFOLFOX6 arm, driven primarily by higher rates of nonhematologic toxicity (69.4% vs 54.5%), including grade 3 or 4 fatigue (10.1% vs 3.3%).

Hematologic toxicities of grade 3 or 4 were observed in 46.8% of atezolizumab-treated patients vs 38.6% with mFOLFOX6 alone, with grade 3 or 4 decreases in neutrophil count occurring in 43.6% vs 35.9%, respectively. Analysis of adverse events by treatment phase showed that neutropenia rates during the mFOLFOX6 portion of treatment were similar between arms (30.1% vs 35.9%), with the higher overall neutropenia rate in the atezolizumab arm largely attributable to the atezolizumab monotherapy phase. Chemotherapy exposure, including median number of cycles and dose delivery, was similar between arms, indicating that the addition of atezolizumab did not compromise delivery of the chemotherapy backbone.

Immune-related adverse events of note, including hypothyroidism, hyperglycemia, colitis, and maculopapular rash, occurred at rates at least 5 percentage points higher in the atezolizumab arm, though grade 3 or 4 immune-related events were not clinically significantly different between arms. Grade 5 events occurred in 6 patients in the atezolizumab arm and 2 in the mFOLFOX6 arm; 2 deaths in the atezolizumab arm were considered treatment-related by the investigator.

ATOMIC Trial Design and Patient Characteristics

ATOMIC was a phase 3, international, randomized trial. Eligible patients were aged 12 years or older with completely resected (R0), histologically confirmed, stage III colon adenocarcinoma and dMMR status confirmed by local immunohistochemical testing. Patients were enrolled within 10 weeks after surgery and randomly assigned 1:1 to receive atezolizumab 840 mg intravenously every 2 weeks for 12 cycles plus mFOLFOX6 for 6 months, followed by atezolizumab monotherapy for 13 additional cycles (12 months of atezolizumab total), or mFOLFOX6 alone for 12 cycles. Randomization was stratified by node stage (N1 or N1c vs N2), tumor stage (T1, T2, or T3 vs T4), and tumor location. A total of 712 patients were enrolled from September 2017 through January 2023.

The median patient age was 64 years, 55.1% were women, 83.7% had proximal tumors, and 53.9% had high-risk disease (T4, N2, or both). Baseline characteristics were well balanced between the two groups, and the demographic and clinical profile of the trial population was comparable to a large National Cancer Database cohort of patients with dMMR stage III colon cancer, supporting the generalizability of the findings. The ATOMIC results have already been incorporated into the most recent National Comprehensive Cancer Network guidelines, which also extend the findings to T4bN0 stage II cancers, and they support the broader adoption of universal MMR testing in all patients with newly diagnosed colon cancer.

"One in three patients with stage III colon cancer will relapse within five years, underscoring the need for new adjuvant treatment options," Michael Sapienza, CEO, Colorectal Cancer Alliance, stated in the news release.¹ "This milestone represents a critical step toward a reality where treatment is tailored to a patient's specific tumor biology from the very beginning, giving them a better chance of preventing a recurrence."

REFERENCES

1. Roche. FDA grants Priority Review for Roche's Tecentriq for a certain type of stage III colon cancer. Press release. June 11, 2026. Accessed June 11, 2026. https://www.roche.com/media/releases/med-cor-2026-06-11

2. Shields AF, Lenz HJ, Meyerhardt JA, et al. Atezolizumab plus mFOLFOX6 for stage III mismatch repair-deficient colon cancer. N Engl J Med. 2026. doi:10.1056/NEJMoa2600001