Cancer is not a disease. Not, at least, in the traditional meaning that we give to that word. Cancer is, in reality, a huge set of ills, ailments and diseases that only have a relative family resemblance. That is why it is such a terrible challenge, such a disproportionate medical challenge. Especially the worst cancers.
In locally advanced rectal cancer, for example, the heavy artillery needs to be brought out. Its usual treatment requires not only neoadjuvant chemotherapy and radiation, but also a surgical resection of the rectum that leaves the patient’s digestive system permanently affected. But what if, from now on, just one drug was enough?
Surprisingly good treatment. That is what the team of Andrea Cercek, an oncologist at the ‘Memorial Sloan Kettering Cancer Center’ in New York, has presented at the annual meeting of the American Society of Clinical Oncology (and in the latest issue of the New Journal England of Medicine). The results that indicate that Dostarlimab, a monoclonal antibody that blocks the receptor for programmed cell death protein 1 (PD-1), “has been shown to be capable of achieving a complete clinical response in locally advanced rectal cancer with repair deficiency of mismatches”.
When we can’t repair the damage. The study has focused on a very specific type of rectal adenocarcinomas (between 5 and 10%) that are caused by a deficiency in mismatch repair. What happens in these cases is that patients have certain mutations in a specific group of genes responsible for various DNA repair processes in cells. Without these repair processes, the failures accumulate and this produces the growth of polyps and tumors at a fairly early age. Furthermore, as if that weren’t enough, these tumors have been shown to respond poorly to standard chemotherapy regimens, including the most advanced procedures.
One is that, in other colorectal cancers (both metastatic and refractory to treatment), immune checkpoint blockade alone is very effective. We are talking about objective response rates ranging from 33% to 55%, and prolonged overall survival. On that basis, they had an idea.
“We hypothesized that blocking programmed death 1 (PD-1) with a single agent might be beneficial in locally advanced rectal cancer deficient in mismatch repair.” That’s where dostarlimab came in. For six months this treatment was administered in patients with stage II or III rectal adenocarcinoma. The result has been impressive.
100% remission in six months. Above all, because according to the initial plan, after this treatment, the patients had to undergo cycles of standard chemoradiation therapy and surgery, but it was not necessary. Of the 12 patients who completed treatment, 12 achieved complete tumor remission. I put it in percentages to make it clear: 100%.
And, up to 25 months after finishing dostarlimab treatment, remission continues for all patients. There is no doubt, as the same authors point out, that patients need “longer follow-up to assess the duration of response.” Above all, because the study is very small, but it opens up a very interesting field to treat some of the most lethal cancers that we know of.
