This transcript has been edited for clarity.
Hello. I’m David Kerr, professor of cancer medicine at University of Oxford. I’d like to talk about the ATOMIC trial that was presented recently at ASCO by a good pal of mine, Frank Sinicrope, from the Mayo Clinic.
We don’t often talk about the latest ASCO results on these Medscape videos, just because we get so much information. Those of us who are ASCO/ESMO members get bombarded — I think, appropriately — from these fantastic societies. I thought this was worthwhile given the fact that it’s potentially practice changing.
The ATOMIC study was of standard adjuvant chemotherapy for [patients with] stage III colon cancer, who had deficient mismatch repair/microsatellite unstable or MSI high tumors — those which we know are responsive to immunotherapy in the advanced setting. They were randomized to either chemotherapy alone for 6 months, 12 cycles of FOLFOX infusion (5-FU oxaliplatin chemotherapy), or the same chemotherapy plus the PD-L1 inhibitor atezolizumab.
The atezolizumab was given in combination with FOLFOX for the first 6 months and then continued as monotherapy for a further 6 months. It’s an NCI-sponsored trial from a fantastic collaborative group, and they managed to randomize 712 patients over 6 years.
The trial started in 2017, and the last patient was recruited early in 2023. During that period of time, practices changed somewhat. We tend, by and large, to give 3 months rather than 6 months of adjuvant chemotherapy. The trial was of its time, though, and it was well designed.
Disease-free survival was a primary outcome. They demonstrated that, in the atezolizumab arm, the disease-free survival was 86.4% compared with 76.6% in the FOLFOX arm, showing a very high P value and a very decent hazard ratio, as one would expect.
Frank and colleagues concluded that, given the advantages accrued by the addition of atezolizumab to FOLFOX, in terms of disease-free survival, this should be considered a new adjuvant standard of care for patients with mismatch repair-deficient colon cancer.
Yes, but no. Yes, but as I said, we tend to give 3 rather than 6 months adjuvant chemotherapy. Do we need to give chemotherapy for that long? We would argue probably not.
What about atezolizumab on its own? Could that be as effective as in combination with chemotherapy? One wonders. For atezolizumab, should it be 12 months or 6 months or 24 months? There’s something very interesting about the duration of exposure to atezolizumab, and of course, we’d have to look at the cost effectiveness of how we do that.
Well done, Frank and team, and to the ATOMIC study group. These are very provocative data and a highly significant finding in terms of disease-free survival. Let’s see what happens with more follow-up on overall survival, that will be an important additional set of secondary endpoints.
There are still a number of important questions to ask in terms of toxicity of the combination, duration of therapy, and possibly financial toxicity given the cost of an immune checkpoint inhibitor. This was an important study and possibly a landmark in terms of how we treat this.
It’s relatively rare. Remember, only about 10% of our colon cancers will be mismatch repair deficient. It was a good trial and well run.
I’d be really interested in your comments. Am I being too hard? Or should we just accept this as a new gold standard?
Thanks for listening, Medscapers. For the time being, over and out. Thank you.