At the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr Frank Sinicrope (Mayo Clinic, Rochester, MN, USA) presented pivotal results from the phase III ATOMIC trial. The study evaluated the addition of the anti–PD-L1 antibody atezolizumab to standard adjuvant FOLFOX chemotherapy in patients with stage III colon cancer and deficient mismatch repair (dMMR). Given the immunogenic nature of dMMR tumours, the trial aimed to enhance immune response post-surgery. The combination therapy reduced the risk of recurrence or death by 50%, with a promising safety profile and could now redefine the standard of care for this high-risk patient group.

The late-breaking abstract, ‘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)’ (LBA1) was presented at the American Society of Clinical Oncology on May 30 to June 3 2025 in Chicago, IL, USA.

Questions

1. What was the rationale behind combining atezolizumab with standard chemotherapy in dMMR stage III colon cancer? (0:18.33)
2. What was the design and methodology of the trial? (0:58.16)
3. What are the most significant findings, and were there any notable safety or tolerability concerns when combining atezolizumab with FOLFOX in the adjuvant setting? (2:21.76)
4. Could these findings change the future standard of care in stage III dMMR colon cancer? (3:42.72)
5. What questions remain unanswered, and are there future studies planned? (5:58.15)

Transcript

Hello. My name is Dr Frank Sinicrope, and I am a GI medical oncologist at Mayo Clinic in Rochester, Minnesota.

So colorectal cancers with deficient mismatch repair are hyper mutated tumours, and this results in the body, the immune system, recognizing the tumour as foreign and creating a very pronounced inflammatory reaction. And a lot of these immune cells and some tumour cells will express PDL-1. And when checkpoint inhibitors were developed that target PD-1 and PD-L1, then the idea became to try to see, if we could, utilize these drugs to enhance the immune system’s ability to eradicate the tumor.

Q2. What was the design and methodology of the trial?

So the ATOMIC trial was designed to compare chemo immunotherapy versus chemotherapy alone. And so the experimental arm was standard FOLFOX chemotherapy given for twelve cycles or six months combined with atezolizumab, an anti-PD-L1 antibody, and then the atezolizumab was continued for an additional six months as monotherapy.

So a total of one year duration of immunotherapy in the experimental arm. The control arm was was modified FOLFOX alone for twelve cycles or six months. And this trial was designed with a hazard ratio of 0.6, and when we did the power calculations, it required about 700 patients.

And so, this number of patients was randomized 1:1 to the two arms of the study. We had two interim analyses, one at 50% and the other at 75% of events.

And, this was for efficacy. And at the second interim analysis, the Data and Safety Monitoring Board (DSMB) reviewed the data and decided to release the data for the study.

So we were able to get a readout of the primary endpoint, which was disease-free survival at a median of 37.2 months into the study.

So we observed that the chemo-immunotherapy arm of atezolizumab and FOLFOX resulted in a 50% reduction in recurrence and death compared to FOLFOX alone.

And this was, you know, quite an impressive, risk benefit for the combination arm. And we saw early divergence of the survival curves, and we actually saw plateauing of the atezolizumab FOLFOX arm, you know, indicating that, many of the patients were no longer, recurring or dying, and therefore, we may be curing some of these patients.

We also did retrospective central confirmation of the deficient mismatch repair status of the tumours, and the results we got with that analysis were very, very similar. So we achieved overall hazard ratio of 0.5 with a highly significant p-value of less than 0.0001.

So we regard the findings of this study as practice changing and representing a new standard treatment for dMMR stage III colon cancers.

I do regard the findings of this trial to as establishing a new standard treatment for patients with dMMR stage III colon cancers.

There are some interesting data that will be coming out in the future, related to the AZOR two trial that is ongoing, which looks at immunotherapy for three months.

Patients have surgery, and then they get immunotherapy for an additional six months. And that’s, you know, compared to the surgery and standard adjuvant chemotherapy. So that will be interesting and important data. Many people are, of course, are aware of the neoadjuvant data that has, that has been published including the niche two trial with very provocative, very impressive pathological responses in patients who received limited neoadjuvant combination immunotherapy.

I think that the important point to to realize there is that, while very provocative, those data are not randomized. They’re relatively modest number of patients. The follow-up is still not long enough to ensure that there’s no compromise of long term oncologic outcomes. And, pathologic CR, you know, is not a surrogate for disease free survival. So while the you know, those data are, as I mentioned, are very, very interesting, very encouraging, They’re still somewhat experimental.

And this is in contrast to the ATOMIC trial, which is a a large phase three, you know, clinical trial. ATOMIC was not associated with any unexpected or serious grade three or four adverse events with the exception of some increase in non febrile grade four neutropenia. However, that level of neutropenia was nearly similar to what was achieved in the MOSAIC adjuvant trial. So we found 14% grade four neutropenia. The MOSAIC adjuvant trial with just FOLFOX alone found 12%. So, you know, I think it’s, again, it’s it’s quite manageable in this population.

Yes. So ATOMIC was designed at a time when it was unethical to give just immunotherapy and not give any chemotherapy to a stage III patient. So we do not have a immunotherapy alone arm, and, you know, the question comes up is how would that arm have done? Can we just give immunotherapy alone and not chemotherapy? And the trial cannot specifically answer that question.

I do think, however, that in the control arm, we felt that when we designed the trial, we were generous expecting a 75% percent three-year DFS for the control arm. And in the trial, we actually observed 76-66% percent three-year DFS. So I do believe that the chemotherapy is having some benefit, and is likely due to the oxaliplatin, but we really can’t answer the immunotherapy alone question.

View full #ASCO25 coverage here!

Disclosures: Frank Sinicrope discloses employment at MedVal (I); stock and other ownership interests at Lilly; a consulting or advisory role  with Guardant Health and Roche; institution research funding from Ventana Medical Systems; patents, royalties and other intellectual property: patent royalty related to immune markers in colon cancer. Patent jointly held between himself and Roche/Ventana Medical Systems (Institution).

This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the American Society of Clinical Oncology (ASCO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.

Interviewer/Editor: Sophie Nickelson

Cite: #ASCO25: ATOMIC trial shows atezolizumab halves recurrence in stage III dMMR colon cancer. touchONCOLOGY. June 24th, 2025.

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