A drug causes colon cancer to regress completely in all patients in a study

• Colon cancer office: the unknown test that could save your life

Dostarlimab

, a monoclonal antibody that blocks the receptor for programmed cell death protein 1 (PD-1), which makes it

, has been shown to be capable of achieving a

with mismatch repair deficiency.

And the most novel thing is that the response has been achieved with the

, without radiation or surgery, according to

, a medical oncologist at the Memorial Sloan Kettering Cancer Center in New York, United States, whose team has presented the results of their work at the meeting of the American Society of Clinical Oncology (ASCO22) that is being held in Chicago, and that will be published in the latest issue of

.

Neoadjuvant

and

followed by

of the rectum is usually the standard, multimodal treatment for locally advanced rectal cancer.

Within this, a subset is caused by a

: certain genes carry information that tells the body's cells how to function and that help

DNA damage through a process called repair. of mismatch.

It is estimated that between

of rectal adenocarcinomas are mismatch

deficient , and these tumors have been shown to

standard chemotherapy regimens, including neoadjuvant chemotherapy in locally advanced rectal cancer. .

But,

has also been shown to be highly effective as a first-line treatment for patients with

mismatch repair-poor

, with objective response rates ranging from 33% to 55%, clinically significant duration of response, and prolonged overall survival, is discussed in the article.

"Based on the benefits seen in the setting of metastatic disease, we hypothesized that

blockade of programmed death 1 (PD-1) might be beneficial in locally advanced, protein

-deficient

the repair of pairing errors," says Cercek.

To do this, investigators initiated a prospective phase 2 study in which the anti-PD-1 monoclonal antibody dostarlimab was administered as a single agent

in patients with

repair-deficient rectal adenocarcinoma.

of pairing errors.

This treatment was to be followed by standard chemoradiation therapy and surgery, but patients who had a

after completing dostarlimab therapy would

primary endpoints

"The primary endpoints are

after completing dostarlimab therapy or

after completing dostarlimab therapy with or without chemoradiation therapy and

to neoadjuvant dostarlimab therapy with or without chemoradiation therapy. ", indicate the authors of the investigation.

Based on the data presented, 12 patients completed treatment with dostarlimab and have had at least 6 months of follow-up.

All

, with no evidence of tumor on follow-up examinations: magnetic resonance imaging, F-fluorodeoxyglucose-positron emission tomography (PET), endoscopic evaluation, digital rectal examination, or biopsy.

"At the time of this report, the researchers note, no patients had received

, and no cases of progression or recurrence had been reported during follow-up, ranging from 6 to 25 months, nor Grade 3 or higher adverse events have been reported.

The main observations of the New York team's work conclude that locally advanced, mismatch repair-deficient rectal cancer was

.

However, it also stresses that "

is needed to assess the duration of response."

The included patients had stage II or stage III rectal cancer with mismatch repair deficiency

.

Mismatch repair status was determined using a

for the detection of loss of expression of the MLH1, MSH1, MSH6, and PMS2 genes.

An important question raised by the authors after what was observed in the work is why do these rectal tumors deficient in repair of localized mismatches

colorectal tumors

?

In another study involving patients with metastatic disease who had not previously received any treatment, the image-based

of error-repair-poor colorectal tumors was

"despite the presence of molecular changes at baseline that were

evaluated in our study," says Cercek.

An explanation related to tumors of the gastrointestinal tract is the possible

, since a growing literature supports the immunomodulatory role of certain

in increasing the antitumor immune response potentiated by blockade of checkpoints.

gut microbiome

Thus, a neoadjuvant checkpoint blockade study in NSCLC showed that high numbers of

intestinal

species were associated with a

.

has further been found to

be associated with an

in mismatch repair.

It is therefore speculated that, in addition to the tumor cell intrinsic factor that drives the response to PD-1 blockade - that is, the extremely high tumor mutational burden associated with mismatch repair deficiency - there is a

to the tumor cell, such as the

, which may be driving this

.

For the researchers, "intrinsic characteristics of tumor cells beyond tumor mutational load, such as clonality, aneuploidy, and mutation class, which have been shown to

, may affect differences in response between localized and metastatic disease.

Cercek indicates that although the results of our study are

, especially since 12 consecutive patients had a complete clinical response, the

.

These findings need to be

that balances academic and community practices and ensures the participation of patients from diverse racial and ethnic backgrounds.

"Once available, data on the duration of complete response, the study's other primary endpoint, will address the question of whether this approach, in the long term,

Optimism and unknowns

dropdown

In an

appearing in the latest

,

, Division of Oncology, Cancer Center, University Chapel Hill, North Carolina, discusses the results of "a small, but compelling study" describing

in patients with stage 2 or 3 rectal cancer with mismatch repair.

In his opinion, the results "are cause for great optimism" but such an approach

.

The stated endpoint, complete clinical response, "is an imperfect surrogate for long-term cancer control."

Patients who have a complete clinical response after chemotherapy and radiation therapy have a better prognosis than those who do not have a complete clinical response, but "

of such patients when the cancer is treated

."

In his opinion, these recurrence dynamics may or may not differ between immunotherapy and chemotherapy and radiotherapy and between

.

"In fact, very little is known about the time it takes to know if complete clinical response to dostarlimab equates to cure."

At this time, Sanoff believes it is unknown whether the results of this small study conducted at Memorial Sloan Kettering Cancer Center can be

of rectal cancer patients.

"In order to provide more information about which patients might benefit from immunotherapy, further trials should

, coexisting conditions, and tumor characteristics. Enrolling patients from diverse communities could also address

that are known to influence the response to immunotherapy.

The author of this editorial does not forget that the

is also essential to ensure that this is a safe approach to implement on a large scale.

"Safe non-surgical management implies

to perform direct intraluminal visualization as well as to interpret rectal MRI data, procedures not available in all centers. Without them, patients

if new tumor growth occurs.

Despite these uncertainties, however, the editorial acknowledges the work of Cercek's team, "with a promising but unknown future with immunotherapy that has provided what may be an

in which However, the serious

with PD-1 inhibitors, which are usually greater than those observed in this study

, cannot be forgotten ."

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