Immunotherapy May Let a Tested Few Rectal Cancer Patients Avoid Chemotherapy, Radiation, and Surgery

For a person diagnosed with locally advanced rectal cancer, the standard path has long been demanding. In modern practice it is usually a combination of chemotherapy and radiation, given in varying sequences, followed by surgery to remove the affected part of the rectum.

That path saves lives. It also carries consequences that patients live with for the rest of their lives.

Chemotherapy and radiation before surgery can affect bowel, urinary, and sexual function, as well as fertility, a consideration of growing importance as rectal cancer is diagnosed in younger adults. Surgery carries risks of serious complications, including poor healing and leaks where the bowel is reconnected. For some patients, particularly those with tumors low in the rectum, it ends with a permanent colostomy.

Specialist centers already offer a form of organ preservation to selected patients whose tumors disappear completely after standard chemotherapy and radiation: close surveillance instead of immediate surgery, often called watch and wait. But reaching that point has always required enduring the chemotherapy and radiation first.

Against that background, the question researchers have been asking is a significant one: for a defined group of patients, can the immune system do the work from the start, before any of the standard treatments are given?

For patients whose tumors are mismatch repair deficient, known as dMMR, or microsatellite instability high, known as MSI-H, the evidence now points toward yes, at least for a meaningful share of them.

A Treatment Built on a Measurable Difference

The approval applies only to previously untreated stage II or stage III tumors with the dMMR or MSI-H marker, identified through a test authorized by the FDA. Published estimates suggest that approximately 3% of locally advanced rectal cancers carry this marker. Patients whose cancer has spread to distant organs are not covered by this approval.

Both terms describe a defect in the way cancer cells correct errors when copying their DNA. A healthy repair system catches and fixes those mistakes. When the system fails, errors accumulate and produce proteins that the immune system can recognize. That visibility makes these tumors particularly vulnerable to immunotherapy.

Jemperli is a monoclonal antibody that blocks PD-1, a checkpoint protein on immune cells. Tumors exploit PD-1 as a shield against immune attack. Blocking it removes the shield and allows the patient's own immune system to act against the tumor.

The biology matters for a practical reason. This is not a treatment offered to every rectal cancer patient and then judged on hope. Eligibility is determined by a laboratory result, and the treatment is reserved for the patients whose tumors show the marker.

According to GSK, the approval makes Jemperli the first and only immunotherapy approved in the United States for this patient group. The FDA granted the application Priority Review and had earlier given the therapy Breakthrough Therapy and Fast Track designations.

What the Studies Found

The FDA based its decision on interim results from AZUR-1, a phase 2, single arm, open label study of Jemperli alone in 154 patients with previously untreated dMMR or MSI-H locally advanced rectal cancer. Patients received 500 mg of the drug intravenously every three weeks for nine cycles, over approximately six months.

The study's primary measure was sustained clinical complete response at 12 months: no detectable cancer, confirmed by endoscopy, rectal MRI, and CT imaging, still present a full year after the response was first observed.

GSK reported investigator assessed results in which 68% of evaluable patients (98 of 144) achieved that sustained complete response at 12 months. In a further exploratory analysis, 76% of evaluable patients (110 of 144) had no evidence of cancer one year or more after treatment. That figure combines the patients who reached a complete response without surgery and 12 patients whose complete response was confirmed in tissue removed at surgery. The company reported no disease recurrences among responders after a median follow up of more than two years.

The FDA's own summary of the interim data states that, after a median follow up of more than two years, almost three fourths of patients in the study had not needed surgery, radiotherapy, or chemotherapy.

Two features of the evidence deserve emphasis, because they shape how much weight the results can carry. AZUR-1 has no comparison group: every patient received Jemperli, so the study cannot directly measure how these patients would have fared on standard treatment. And the figures above come from the 144 patients evaluable for the response analysis, out of 154 enrolled. Neither point undermines the result, and both belong in an honest account of it.

An earlier study at Memorial Sloan Kettering Cancer Center, a single center study of 50 patients with the same tumor profile, found that none of the patients had detectable signs of cancer after treatment with Jemperli alone, and 93% maintained that status for at least 12 months. Of the 27 patients in that study followed for at least three years, one had a recurrence, in the same area as the original tumor.

Angelo de Claro, M.D., director of the FDA's Oncology Center of Excellence, described the decision this way: "Standard treatment for rectal cancer has major life changing effects. For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy."

Acting FDA Commissioner Kyle Diamantas noted that the review was completed nearly four months ahead of schedule, and that some patients who might otherwise be preparing for surgery, radiation, or chemotherapy may now have a different conversation with their doctor.

The Approval Comes With Conditions

The strength of the results should be read alongside the structure of the approval, because the FDA's decision is an accelerated approval, and that term carries specific meaning.

Accelerated approval is granted on interim evidence when a treatment shows strong early results for a serious condition. It is not the final word. The sponsor is required to continue following patients to confirm that the responses produce lasting clinical benefit, and continued approval depends on that confirmation.

Several questions remain open. The durability of the responses over five and ten years is not yet known. How often the cancer returns after a complete response, and how quickly it can be caught when it does, will only become clear with longer follow up. The FDA itself notes that longer follow up is needed to understand the duration of response and how often the cancer returns.

The treatment pathway also places a new weight on monitoring. Patients who achieve a complete response enter non operative management, which means structured surveillance rather than surgery: repeated endoscopy, MRI, and clinical assessment on a set schedule, every four months for the first two years in the AZUR-1 study and every six months afterward. Patients who do not achieve a complete response, or whose cancer returns or progresses, are evaluated for standard treatment. Avoiding surgery does not mean avoiding care. It means trading one demanding pathway for another that depends on disciplined follow up, with standard treatment held in reserve if the cancer reappears.

The drug also carries the risks associated with immune based therapy. Because Jemperli releases the immune system, it can provoke immune reactions against healthy organs and tissues, which can arise during or after treatment and can be severe or, in rare cases, fatal. The most common side effects reported in this patient group, each in at least 15% of patients, were fatigue, rash, diarrhea, and itching.

None of this diminishes the result. It defines how the result should be used: by the right patients, in centers prepared to test, counsel, and monitor them properly.

Testing Becomes the First Decision

The most consequential implication of this approval may not be the drug itself. It may be the test.

No patient can reach this option without a dMMR or MSI-H result. That makes biomarker testing the first decision in the care of every newly diagnosed locally advanced rectal cancer patient, rather than a consideration that arises later in treatment planning.

For health systems, that has operational consequences. Pathology services must be able to perform or obtain the testing promptly, because treatment sequencing now depends on the result. A patient who begins standard chemotherapy and radiation before the marker is known may lose the opportunity this pathway offers, or face a more complicated decision about changing course.

For patients, the implication is equally direct. Two people with the same diagnosis and the same stage may now be offered fundamentally different treatments, based on a laboratory finding. Explaining that difference, and the uncertainty that accompanies an accelerated approval, becomes a central part of the clinical conversation.

There is also an access question that the American healthcare system should not leave to chance. If testing is prompt and routine in major cancer centers but slower or less available elsewhere, the benefit of this approval will not be distributed evenly. The science has identified who can benefit. The system's task is to make sure those patients are actually found.

What This Means for the American Healthcare Ecosystem

This approval illustrates a pattern that is becoming familiar in modern medicine. Progress increasingly arrives in precisely defined groups: a specific marker, a specific stage, a specific treatment sequence. The gains for the patients inside those groups can be large. The responsibility of the wider system is to build the testing, referral, and monitoring capacity that allows the right patients to reach the right treatment at the right time.

It also reinforces the importance of honest communication around early evidence. Patients deserve to hear both halves of the story: that roughly three fourths of patients in the pivotal study had avoided the most burdensome parts of standard treatment after two years, and that the approval is interim, the study had no comparison group, the follow up is still maturing, and the monitoring commitment is real.

For the American Chamber of Health, developments of this kind reinforce the value of collaboration among oncologists, surgeons, pathologists, health system leaders, and patient communities. A result produced in a clinical trial becomes a benefit in practice only when laboratories can test, clinicians can counsel, and institutions can organize surveillance for patients who choose the non operative path, and can move quickly to standard treatment for those who need it.

The opportunity is significant precisely because the population is small. A health system does not need to rebuild its cancer program to serve these patients well. It needs to make testing automatic, make the counseling honest, and make the follow up reliable.

A Different Conversation

Rectal cancer treatment has been organized for decades around a sequence few patients would choose if a credible alternative existed. For a defined group of patients, a credible alternative now exists, supported by regulatory review and by results that have held up through more than two years of follow up.

The alternative is narrower than the headlines may suggest. It applies to roughly 3% of locally advanced rectal cancers, it rests on interim data from a study without a comparison group, and it asks patients to accept structured monitoring in place of surgery.

Within those limits, it changes something fundamental. The first conversation after diagnosis is no longer only about how a patient will endure the standard path. For patients whose tumors carry the marker, it can begin with whether they need that path at all.

The measure of this approval will not be the announcement. It will be whether every patient who qualifies is tested, counseled honestly, and followed with the same rigor that produced the result.

Sources and Editorial References

1. U.S. Food and Drug Administration | October 19, 2026
FDA Approves Immunotherapy That May Allow Certain Patients with Rectal Cancer to Avoid Chemotherapy, Radiation and Surgery
Press announcement describing the accelerated approval, the eligible population, the standard treatment burden, the AZUR-1 interim results, the earlier Memorial Sloan Kettering study, side effects, and the conditions attached to the approval.
https://www.fda.gov/news-events/press-announcements/fda-approves-immunotherapy-may-allow-certain-patients-rectal-cancer-avoid-chemotherapy-radiation-and

2. U.S. Food and Drug Administration | October 19, 2026
FDA Grants Accelerated Approval to Dostarlimab for Locally Advanced Rectal Cancer
Approval notification describing the AZUR-1 trial design (multicenter, single arm, open label, 154 patients), the 500 mg dosing schedule, the response assessment methods, the sustained clinical complete response endpoint, and the non operative management schedule.
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-locally-advanced-rectal-cancer

3. GSK | October 19, 2026
Jemperli (Dostarlimab) Approved in US as First and Only Immunotherapy for Adults with MSI-H/dMMR Locally Advanced Rectal Cancer
Company announcement reporting investigator assessed AZUR-1 results, including the 68% sustained clinical complete response figure (98 of 144 evaluable patients) and the 76% no evidence of disease figure (110 of 144). Company reported figures are presented as reported and are identified as such in the article.
https://us.gsk.com/en-us/media/press-releases/jemperli-dostarlimab-gxly-approved-in-us-as-first-and-only-immunotherapy-for-adults-with-msi-hdmmr-locally-advanced-rectal-cancer/

Editorial Disclosure

This article is an independent industry briefing prepared by the American Chamber of Health Editorial Department. It draws on the FDA's published approval announcement and approval notification, and on results reported by the study sponsor.

Figures concerning treatment response, follow up, and recurrence are attributed to the sources identified above. The American Chamber of Health has not independently audited those figures or conducted clinical evaluations of the treatment discussed.

This approval is an accelerated approval based on interim trial results from a single arm study without a comparison group. Statements describing potential benefit are distinguished from established long term outcomes wherever relevant, and continued approval depends on confirmatory evidence.

The analysis reflects the American Chamber of Health's editorial perspective and does not constitute medical advice or an endorsement of GSK or of any specific treatment. Patients should make treatment decisions with their own physicians.