Groundbreaking Advancements in Colorectal Cancer From the Past 25 Years

At the 2023 World Congress on Gastrointestinal Cancers, Alberto Sobrero, MD, Ospedale San Martino, Genova, Italy, highlighted key advancements in colorectal cancer from the past 25 years.

Addressing dostarlimab, non-operative management, liquid biopsies, and checkpoint inhibition, Dr Sobrero concluded these advancements have improved “the concept of [the] continuum of care” allowing not only for prolonged survival for this patient population, but also “patient empowerment” through “shared decision making.”

Transcript:

Good morning, my name is Alberto Sobrero, I'm the head of the medical oncology unit in Genova, Italy, and I'm here [as part] of the invited faculty to cover the topic of 25 years of progresses in colorectal cancer management.

I have organized my analysis into distinguishing between those that can be accounted for as incremental advances, as opposed to those that are real superstars, and in between I have recognized a category of advancement that are a bit more than incremental, but not so much to qualify as a superstar so I have taken this approach in the full lecture that I have given.

For this summary, I will start out with the most outstanding advancement in the last 25 years and that has to deal with the adjuvant setting of rectal cancer. There, there is no doubt— Actually in my opinion, this has been the most outstanding advancement in the whole field of oncology, not only GI oncology, but of oncology, and that is the results with dostarlimab in the neoadjuvant setting of rectal cancer. Now, just think, 36 out of 36 patients being treated without surgery, without radiotherapy, without chemotherapy and going into complete response, not needing mutilating surgery. I mean, to me, this interview could finish there essentially because that type of improvement is so outstanding, so inconceivable 20 years ago, but not even 5 years ago, or 2 years ago, when the data started coming out. No question, that is the most incredible advancement that we have had.

In terms of neoadjuvant rectal cancer, two other paradigm changing type of advancements can be recognized in the non-operative management of approach, as well as the total neoadjuvant treatment of rectal cancer, that because they have changed our way of approaching this disease. When I see a patient for the first time, the first question is, “am I going to treat this patient operatively, or am I considering the non-operative treatment,” so, that's exactly at the beginning of my management. We move to adjuvant colon. Certainly, the data for neoadjuvant treatment with the checkpoint inhibitors, more specifically ipilimumab-nivolumab, for 6 weeks before surgery, the NICHE-2 trial on 100 patients say, again they are kind of superstar type of results. Although, surgery for colon is not the same as surgery, and mutilation, and damage, and complications, as surgery for rectal. The impact of this is not so revolutionary, still it will change our paradigm, and there is a bright future for this type of approach.

The second, impressive advancements that we have witnessed in the last 2 to 3 years has been the coming of the liquid biopsy in the adjuvant setting because it qualifies for a new stage of the disease, the minimal residual disease state, that allows a lot of new ways of interpreting and studying, with new trials, the adjuvant condition.

Third and last point, are the advancements in the field of advanced colorectal cancer treatment. There, we can distinguish 2 superstars. Number 1, surgery. However, 25 years ago, we already had surgery and if you look at the data, 25 years ago, the outcome data from surgical management of liver metastases were not so different from those that we have now. Somehow, surgery continues to be a superstar, but the progresses have not been made so much in this field, either in the conversion part of potentially resectable liver metastases, and/or in the field of adjuvant post-R0 stage 4.

The next superstar in the management of advanced disease, the implementation of the checkpoint inhibitors for the 5% of patients who are MSI-high. We can summarize the entire literature in a very concise way. If you use one drug in later-lines, you get plateaus at long-terms like 3, 4, 5 years, in the range of 25%. If you use 2 checkpoint inhibitors in later-lines, you get 50% of this plateau. That is what counts most for patients, the long-term effect, not the median, who cares about median when you’re talking to patients, especially when you have the opportunity to afford to them long-term benefit. If you use 1 checkpoint inhibitor in first-line, the KEYNOTE-177 trial, you get 45% PFS [progression-free survival] rate at long-term and if you use 2, Heinz Lenz [MD, Keck School of Medicine of University of Southern California, Los Angeles, California] just published on the Journal of Clinical Oncology, the combination of ipilimumab-nivolumab and that affords a 70% plateau PFS. These are the 2 superstars.

I could conclude saying that, for all the rest, things have changed drastically because 25 years ago, the median survival was not 10 to 11 months, but was already in the 16 to 18 months because we already had on top of fluorouracil, 25 years ago, we also had oxaliplatin and irinotecan. But the concept of continuum of care, implementing intermittent treatment, treatment holidays, rechallenges, third-line, fourth-line, fifth-line, surgery, surgery as a line of treatment, now has led this to a median survival for left-sided, in the range of 35 to 40 months, for right-sided, 6 months less, for RAS-mutated, an additional 6 months less. Still, it's almost a doubling in median survival.

So again, what kind of impact has that? Well, in talking to patient, patient empowerment is so much better, so much more easily realizable, so that the shared decision making is really possible now. Thank you.

Source:

Sobrero, A. 25 Years of Progress in Colorectal Cancer Treatment. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain.