Remission in Every Patient

[George K]

The NEJM article.

For those who don't have access....

BACKGROUND
Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer. A subset of rectal cancer is caused by a deficiency in mismatch repair. Because mismatch repair–deficient colorectal cancer is responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease, it was hypothesized that checkpoint blockade could be effective in patients with mismatch repair–deficient, locally advanced rectal cancer.

METHODS
We initiated a prospective phase 2 study in which single-agent dostarlimab, an anti–PD-1 monoclonal antibody, was administered every 3 weeks for 6 months in patients with mismatch repair–deficient stage II or III rectal adenocarcinoma. This treatment was to be followed by standard chemoradiotherapy and surgery. Patients who had a clinical complete response after completion of dostarlimab therapy would proceed without chemoradiotherapy and surgery. The primary end points are sustained clinical complete response 12 months after completion of dostarlimab therapy or pathological complete response after completion of dostarlimab therapy with or without chemoradiotherapy and overall response to neoadjuvant dostarlimab therapy with or without chemoradiotherapy.

RESULTS
A total of 12 patients have completed treatment with dostarlimab and have undergone at least 6 months of follow-up. All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. At the time of this report, no patients had received chemoradiotherapy or undergone surgery, and no cases of progression or recurrence had been reported during follow-up (range, 6 to 25 months). No adverse events of grade 3 or higher have been reported.

CONCLUSIONS
Mismatch repair–deficient, locally advanced rectal cancer was highly sensitive to single-agent PD-1 blockade. Longer follow-up is needed to assess the duration of response.

[brenda]

Very exciting to hear this. I hope the follow-up groups of patients have such great results to confirm this small group's experience.

[kluurs]

ASCO (American Society of Clinical Oncology) is meeting right now - so there will be a lot of exciting stories out there.

[Mik]

Wow. That’s just unheard of, should it hold true.

[bachophile]

Yea this publication in the nejm has been making the rounds. The real question is, does a complete response translate to better survival. That’s been shown to be true in melanoma and breast, not yet in colorectal. While a complete path response (meaning at surgery no viable tumor) is obviously a good thing, there is no guarantee that means there will be less distant recurrence (meaning metastases) and longer survival. Only long term follow up of a number of years will show that but it’s encouraging.

Although this is really a small subset of the rectal cancer population, the ones characterized as dMMR/MSI high (about 15% tops), and we know these tumors are immunotherapy sensitive, what makes this study unique, something u don’t see everyday, is 100% complete response. I think that’s why the New England picked up on it even though it’s a small number of patients (12, don’t know why the nyt reported 18) with a short follow up.

[bachophile]

@kluurs said in Remission in Every Patient:

ASCO (American Society of Clinical Oncology) is meeting right now - so there will be a lot of exciting stories out there.

I often went to ASCO (and met up with Dr G) in the past, always in Chicago. I’ve been forced for professional reasons to go to more surgical conferences and that doesn’t leave time for the medical ones so much. In October I go to Bordeaux France for the European society of surgical oncology meeting and the following March to Boston for the American counterpart meeting. It’s because of some professional obligations which make my presence there somewhat mandatory.

[George K]

@bachophile thanks for your input. As I re-read the article, or at least the abstract, it also became apparent to me that remission≠cure and survival.

I was not aware, because this is way, way, out of my wheelhouse that this tumor is immunosensitive.

Nevertheless, despite the small group, it's encouraging.

[Jolly]

@bachophile said in Remission in Every Patient:

@kluurs said in Remission in Every Patient:

ASCO (American Society of Clinical Oncology) is meeting right now - so there will be a lot of exciting stories out there.

I often went to ASCO (and met up with Dr G) in the past, always in Chicago. I’ve been forced for professional reasons to go to more surgical conferences and that doesn’t leave time for the medical ones so much. In October I go to Bordeaux France for the European society of surgical oncology meeting and the following March to Boston for the American counterpart meeting. It’s because of some professional obligations which make my presence there somewhat mandatory.

Well, dammit, I guess if you have to suffer for your profession, Bordeaux might not be too bad. Boston, well...

[bachophile]

@George-K also to be very honest, the times use of the term remission is not accurate. Remission is usually reserved for hematoligcal malignancies like leukemia. Solid tumors are judged on pathological response to therapy. Complete response. Partial response. No response. Progressive disease.

It’s maybe semantics but to my ear sounds foreign. Because as u say, this is exactly my wheelhouse. Rectal tumors don’t go into remission. They either respond or don’t.

[bachophile]

@Jolly I don’t mind Boston. But it’s not Bordeaux.

[Mik]

Another small step in the right direction.

But I think the public still somehow believes there will be ONE cure for cancer.