Cancer Breakthrough? Jemperli vs. Surgery for Some Patients

We rarely, if ever, write the words “cancer breakthrough.” That’s because such treatments are few and far between. But a report in the New England Journal of Medicine (April 27, 2025) has us excited. That’s because the authors have done some elegant research and have demonstrated surprisingly positive results.

A journalist we respect, Gina Kolata of the New York Times, is also careful when writing about a potential cancer breakthrough. She quoted one of the giants in cancer research, Dr. Bert Vogelstein (New York Times, April 27, 2025). He is a cancer specialist at John Hopkins University School of Medicine. He told Gina that the results of this research were “groundbreaking.”

Gina goes on to describe the outcome of the new clinical trial:

“The result was stunning, and could bring hope to the limited cohort of patients contending with these cancers” [solid tumors of the rectum, esophagus, stomach, urinary tract, endometrium and prostate gland with mismatch repair mutations.]

Changing a Cancer Treatment Paradigm:

The cancers that were treated with the immunotherapy drug dostarlimab (Jemperli) included esophagus, stomach, colon, rectum, bladder and prostate. These cancer patients had what are called tumors with mismatch repair mutations in their genes (dMMR). That can make these cancers more susceptible to immunotherapy. And that is exactly what the investigators discovered. I will describe mismatch repair mutations in more depth momentarily.

But first, why is this research a game changer, a potential cancer breakthrough? Solid tumors such as those mentioned above are almost always treated first with surgery. For decades, the mantra for cancer treatment has been to 1) remove the cancer with surgery hoping that you can “get it all.” That is often followed by 2) chemotherapy and possibly even 3) radiation.

Even after all that, far too many people still die from metastases linked to the original solid tumor. For those that respond positively to such treatments, quality of life can be profoundly impacted. That’s not to say that standard treatment doesn’t save many lives. It does. But it’s not as good as we would like.

What makes the new research so unique were the results of immunotherapy alone. The investigators from the Memorial Sloan Kettering Cancer Center in New York City just used the drug dostarlimab (Jemperli) without surgery. One of the authors, Luis Diaz Jr., MD, a gastrointestinal medical oncologist heads the Division of Solid Tumor Oncology at MSK. He specializes in colon and pancreatic cancers. Dr. Diaz has described the results of this research as a “complete paradigm shift.”

How Could Dostarlimab (Jemperli) Be a Cancer Breakthrough?

Let’s start with the 49 patients who had rectal cancers. These can be very challenging tumors. They frequently get the full spectrum of treatment: surgery, chemotherapy and radiation. According to the American Cancer Society, the overall 5-year survival rate for rectal cancer is 67%. If the cancer is localized, though, the 5-year survival can be as high as 90%. In “regional” tumors, the survival rate is listed as 74%. If the cancer has spread, however, the 5-year rate drops to 18%.

The patients recruited for this study had a “newly diagnosed Stage I, II, or III solid tumor…” They would normally have been initially referred to a surgeon for resection of the cancerous tissues.

Cancer Breakthrough for Rectal Cancers with dMMR:

There were 49 patients in the MSK (Memorial Sloan Kettering) trial (“cohort 1”) who had diagnosed rectal cancer. These were people with a very specific kind of solid cancer, referred to as “mismatch repair-deficient (dMMR) tumors”. They are highly sensitive to immunotherapy (called immune checkpoint PD-1 blockade). Their tumors were labeled “locally advanced rectal cancer.”

The results were dramatic. Of the 49 patients with rectal cancers, the tumors became undetectable within 6 months. More impressive, there were no recurrences within the five years of the trial. That, dear reader, is impressive!

Was There a Cancer Breakthrough for the Other Cancers?

It’s hard to beat the results of the rectal cancer part of this clinical trial. But remember, there were other patients with solid tumors in this study. Their tumors affected the esophagus, stomach, colon, bladder, prostate and endometrium.

In their own words, the authors of the article in the New England Journal of Medicine (April 27, 2025) wrote:

“Among the 103 patients who completed treatment across both cohorts, 84 had a clinical complete response, and 82 did not undergo surgery. Among the 117 total patients, recurrence-free survival at 2 years was 92%.”

The Bottom Line on the Research:

The researchers described the treatment results of the immunotherapeutic agent dostarlimab. It is a PD-1 blocker. Patients with Stage I, Stage II or Stage III solid tumors were treated. The investigators reported that the drug was equally effective for most of the cancers treated, though the few patients who did not have a complete response had either prostate or gastroesophageal tumors.

There were 117 patients included in the analysis and 103 patients who completed the full course of treatment.

The authors report:

“It is notable that disease recurrence developed in only five patients. In four of these patients, the recurrence was restricted to the lymph nodes; one patient underwent resection of an isolated lymph node and remained free of disease. The four other patients resumed PD-1 blockade, with three having complete disease regression…”

Such results are impressive.

The Bad News About This Potential Cancer Breakthrough:

The only patients who participated in this clinical trial were “mismatch repair-deficient (dMMR).” That means the tumors had genetic mutations which make it hard for the cells to repair DNA damage. This kind of solid tumor is relatively rare, occurring in about 2% to 3% of cancer patients. The rest of the patients with solid tumors are not expected to fare very well, if at all, by getting Jemperli.

That means, though, that anyone diagnosed with a solid tumor, such as gastrointestinal, esophageal, uterine, prostate, bladder, etc. should have the tumor tested for mismatch repair deficiency. If the cancer has this kind of genetic mutation it would certainly be worth discussing the possibility of employing Jemperli with an oncologist knowledgeable about its benefits and risks.

What About Side Effects?

Cancer drugs have side effects. That is a given. Sometimes those adverse reactions can be life threatening. Patients are often willing to take that risk because the cancer is also life threatening.

In this clinical trial about 40% of the patients did not experience adverse events. The most common complication was fatigue, affecting 23% of patients. Rash or dermatitis affected 21% and itching was a problem for 19% of those participating in the clinical trial.

The authors add:

“The following grade 3 adverse events occurred in one patient each: diabetes, lung infection, hypothyroidism, encephalitis, and neutropenia. Grade 4 febrile neutropenia occurred in one patient.”

Those more serious side effects would appear to have been relatively rare in this study.

One More BIG Downside to This Potential Cancer Breakthrough:

Old habits die hard. Most oncologists have been taught that solid tumors must be cut out first, followed by chemo and/or radiation therapy. Getting them to consider immunotherapy out of the starting gate could be challenging, even with the impressive results of this study.

The lead author of the New England Journal of Medicine study was Dr. Andrea Cercek. She is the Section Head of Colorectal Cancer and founder and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at Memorial Sloan Kettering Cancer Center.

She is quoted by Time Magazine (April 28, 2025):

“The bottom line is that everyone did benefit. No one was harmed. It takes home the message that therapy like this can lead to significant clinical complete responses, tumor downstaging, and significant improvement in the quality of life of patients.”

“I see this as utilizing an incredibly effective approach in early-stage disease where we can use immunotherapy and with the majority of these tumors, replace standard of care and surgery.”

“These weren’t super baby-sized tumors. There were definitely some that were Stage III. But we didn’t see any differences in tumor stage and how patients responded. We think that as long as there is not distant disease, or metastases, patients could benefit.”

But please remember, these patients all had the rare, dMMR-type solid tumors.

Another Downside:

Then there is the cost. This is a very expensive drug. The price is projected around $11,500 per infusion and there would need to be roughly nine infusions administered over six months.

Insurance companies are likely to deny coverage for Jemperli unless guideline committees recommend it for treatment of a specific dMMR solid tumor (with mismatch repair-deficient characteristics). It can take guideline committees a long time to change their recommendations. And that means insurance companies are likely to deny coverage until there is a clear green light from the “experts.” There is also FDA approval to contend with. As I write this, the FDA has rather limited “indications” for the use of Jemperli.

The FDA has approved Jemperli for:

• Endometrial Cancer in combination with chemotherapy or when the tumor is mismatch repair deficient (dMMR).
• Mismatch Repair Deficient Recurrent or Advanced Solid Tumors

What the FDA has not yet approved is early treatment of solid dMMR tumors. That will hopefully change in the near future now that the New England Journal of Medicine has published research that has made headlines around the world.