Dr Sinicrope on the Clinical Implications of the ATOMIC Trial for Stage III dMMR CRC

"With the ATOMIC trial, we have data showing that the addition of immunotherapy to chemotherapy can significantly benefit this patient population. Practitioners will be very eager to implement this regimen into their clinical practice."

Frank A. Sinicrope, MD, coleader of the Gastrointestinal Cancer Program and clinical investigator at Mayo Foundation, discussed the implications of the phase 3 ATOMIC trial (NCT02912559) for clinical practice in stage III, mismatch repair–deficient (dMMR) colon cancer.

, results from the trial demonstrated a statistically significant disease-free survival (DFS) benefit with the addition of atezolizumab (Tecentriq) to standard adjuvant mFOLFOX6 (modified oxaliplatin, leucovorin, and fluorouracil) chemotherapy for this patient population.

At a median follow-up of 37.2 months (Q1-Q3, 24.2-55.7) , the 3-year DFS rate was 86.4% with atezolizumab plus mFOLFOX6 (n = 346) compared with 76.6% with mFOLFOX6 alone (n = 334). This corresponded to a 50% reduction in the risk of disease recurrence or death (HR, 0.50; 95% CI, 0.34-0.72; 

 < .0001). The second interim analysis met the prespecified boundary for efficacy after 75% of DFS events had occurred. The data cutoff was February 4, 2025.

Sinicrope emphasized that although dMMR colon cancer is relatively chemoresistant, this population is known to respond well to immune checkpoint inhibition in the metastatic setting. Until now, data supporting the use of immunotherapy in earlier-stage disease had been lacking, he stated. Findings from ATOMIC now provide the first evidence that immune checkpoint inhibition can improve DFS in the adjuvant setting for patients with stage III dMMR colon cancer, Sinicrope asserted, adding that this represents a potential practice-changing development.

Given the strength of the data, Sinicrope noted that guideline committees are being approached to review the findings for potential inclusion in future treatment recommendations. With updated guidance, oncologists may increasingly adopt adjuvant atezolizumab plus mFOLFOX6 as a new standard for this biologically distinct subset of patients, he concluded.

Videos

Frank A. Sinicrope, MD, discuses the implications of data with atezolizumab plus adjuvant mFOLFOX6 for the management of stage III, dMMR colon cancer.
 

Dr Sinicrope on the Efficacy and Safety of mFOLFOX6 Plus Atezolizumab in Stage III dMMR CRC

"The combination of mFOLFOX6 and atezolizumab resulted in a 50% reduction in recurrence or death in patients [with dMMR CRC] compared with mFOLFOX6 alone. We regard that as a very clinically meaningful difference, and believe that this trial is practice changing."

Frank A. Sinicrope, MD, a gastroenterologist, internist, and oncologist at Mayo Clinic, shared efficacy and safety findings from the phase 3 ATOMIC trial (NCT02912559), which evaluated the addition of atezolizumab (Tecentriq) to adjuvant mFOLFOX6 (modified oxaliplatin, leucovorin, and fluorouracil) in patients with stage III, mismatch repair–deficient (dMMR) colon cancer.

 showed that the combination of atezolizumab plus mFOLFOX6 led to a statistically significant improvement in disease-free survival (DFS) compared with mFOLFOX6 alone. At the second interim analysis, conducted after 75% of DFS events had occurred, the trial met the prespecified boundary for efficacy. At a median follow-up of 37.2 months (Q1-Q3, 24.2-55.7) and a data cutoff February 4, 2025, the 3-year DFS rate was 86.4% with atezolizumab plus chemotherapy (n = 346) vs 76.6% with chemotherapy alone (n = 334), translating to a 50% reduction in the risk of recurrence or death (HR, 0.50; 95% CI, 0.34-0.72; 

 < .0001). Sinicrope stated that these results are “clinically meaningful” and support the adoption of this regimen as a new standard of care for patients with stage III dMMR colon cancer. He also noted that the DFS curve in the combination arm was plateauing, suggesting durable benefit and a lack of continued recurrence over time.

The addition of atezolizumab to mFOLFOX6 resulted in a manageable safety profile consistent with the known toxicities of each agent. The most notable difference was a higher rate of grade 4 neutropenia in the combination arm, which was non-febrile and considered clinically manageable. Sinicrope emphasized that the incidence of neutropenia in the control arm was lower than what has been reported in historical trials using mFOLFOX6, further supporting the tolerability of the combination, he added.

These findings position adjuvant atezolizumab plus mFOLFOX6 as a practice-changing regimen for patients with stage III dMMR colon cancer, Sinicrope concluded.

Frank A. Sinicrope, MD, discuses the efficacy and safety of atezolizumab plus mFOLFOX6 in patients with stage III dMMR colon cancer

Frank A. Sinicrope, MD, medical oncologist, Departments of Gastroenterology and Hepatology and Oncology, Mayo Clinic, discusses patients with metastatic colorectal cancer (mCRC) who are mismatch repair-deficient.

Having mismatch repair deficiency is a good prognostic marker in patients with mCRC, Sinicrope explains, although it appears to be more favorable in stage II disease compared with stage III. There is not yet enough data in mismatch repair deficiency in stage III disease, he adds.

A recent study sought to answer if mismatch repair deficiency was a favorable prognostic marker in patients who received a FOLFOX-based regimen. Data suggested mismatch repair deficiency may be beneficial in these patients, but more studies need to be conducted. It was also found that patients who received a FOLFIRI plus cetuximab regimen did not have the same survival advantage as those with a FOLFOX-based regimen.

Frank A. Sinicrope, MD, medical oncologist, Departments of Gastroenterology and Hepatology and Oncology, Mayo Clinic, discusses patients with metastatic colorectal cancer (mCRC) who are mismatch repair-deficient. 


Frank A. Sinicrope, MD

Articles

Dr Sinicrope on the Clinical Implications of the ATOMIC Trial for Stage III dMMR CRC

Dr Sinicrope on the Efficacy and Safety of mFOLFOX6 Plus Atezolizumab in Stage III dMMR CRC

Dr. Sinicrope on Mismatch Repair-Deficient Patients With Metastatic Colorectal Cancer