Top Colorectal Cancer Studies at #ASCO18

It is time for the annual meeting of the American Society of Clinical Oncology (ASCO), and for those of you going for the first time, you will enjoy a meeting of fantastic scientific quality. Plan ahead. Think of why you really want to go, and focus. Do not exhaust yourself; instead, pace yourself. I can say that as a veteran of many of these meetings. But clearly, ASCO, as well as the annual meeting of the European Society for Medical Oncology (ESMO), provide great breaking news and high-quality work. Enjoy yourselves.

I wanted to mention a few abstracts that caught my eye. In abstract 3509, Michael Geissler, MD, PhD, and colleagues^[1] report on a very interesting study of triple chemotherapy with anti-EGFR, looking at combinations of a modified FOLFOXIRI regimen plus panitumumab versus FOLFOXIRI alone in chemotherapy-naive, front-line, nonresectable, RAS wild-type metastatic colorectal cancer patients.

It’s a nice study design in terms of how you move the regimen forward. There was a 2-to-1 randomization of 96 patients. What really caught my eye was the extraordinary response rate in the combination arm: 85.7% versus 54.5% in the chemotherapy-alone arm.

It is fantastic that if we select patients appropriately, we can achieve response rates at this level. Clearly, this is a regimen that could be very effective in certain patient groups. There are also some subgroup analyses with relatively small numbers, which we should therefore treat with caution. But it’s a study to watch for.

In another interesting abstract, 3507, Katherine Clifton, MD, and colleagues^[2]have done a very nice study using a clever methodology to look at new copy number circulating DNA. They looked for driver mutations in a very large cohort of colorectal cancer patients; almost 5000 patients underwent molecular profiling with a plasma-based, next-generation sequencing assay.

The assay encompassed driver mutations like ROS1, RET, ALK, and some of the FGF receptor fusions. In this well-designed study, they found 41 patients in whom they could detect DNA driver mutations. It was a huge effort and very well done; however, quite a small payback given the effort. Of course, there is no evidence as yet—at least in the abstract—as to whether those driver mutations were of any clinical use.

This raises the question of how much work is still to be done in terms of using next-generation sequencing in precision medicine. There is extraordinary potential for using gene sequencing, but can it actually be parlayed into significant, practical clinical benefit?

Another abstract that caught my eye was 3505, reported by an excellent Italian group with lead author Filippo Pietrantonio, MD.^[3] This study addresses the question of maintenance chemotherapy in patients with RAS wild-type, unresectable, metastatic colorectal cancer. The patients received FOLFOX and panitumumab for eight cycles of induction therapy and then they were randomized to two different maintenance regimens: panitumumab alone or panitumumab plus infusion of 5-FU/leucovorin. They had 229 patients randomized equally across each arm. The study showed a benefit from maintenance with chemotherapy and panitumumab.

This is an area that still fascinates me. In the old days, we published a couple of papers in the Lancet from the United Kingdom in which we randomized patients who were responding or had stable disease to stop or continue chemotherapy until progression. In those rather old-fashioned studies, having a complete chemotherapy break did not interfere or reduce overall survival. And not surprisingly, it was associated with improved quality of life.

Of course, there have been more recent studies from Italy, France, and the Netherlands in which some form of de-intensified maintenance chemotherapy is associated with prolongation of progression-free survival. This is more or less what was shown here—that rather than just use panitumumab on its own, if one is de-intensifying chemotherapy, then use the infusion of 5-FU/leucovorin.

In our clinic, we tend to use capecitabine. And we tend to select patients for maintenance treatment who have a higher metastatic burden or tumor load on presentation; who present with relatively oligometastatic disease that is, for whatever reason, not technically ablatable or operable; and who have a good response to chemotherapy.

For the elderly, the frail, and those who have suffered toxicity with chemotherapy, we would give them a chemotherapy break and reintroduce chemotherapy on progression of disease.

In younger, fitter patients who are tolerating chemo and who had a big initial burden of disease, we would offer a maintenance treatment. A fluoropyrimidine and anti-EGFR inhibitor in RAS wild-type disease would seem entirely reasonable. But think about the possibility of a complete chemotherapy break for those who have more indolent disease and perhaps are less tolerant of chemotherapy.

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