FDA Approval for Dostarlimab: Locally Advanced Rectal Cancer – Surgery, Radiotherapy, and Chemotherapy May Not Be Necessary
In this article
No Surgery, No Radiation, No Chemotherapy: Can Six Months of Immunotherapy Replace Standard Treatment in Rectal Cancer?
On October 19, 2026, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the immunotherapy drug dostarlimab (Jemperli, GSK) for stage II–III locally advanced rectal cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). It is the first immunotherapy approved for curative-intent treatment of rectal cancer. With this approval, an approach in which the drug is given on its own and patients with a complete response are closely monitored without surgery, radiation or chemotherapy has been formally recognized for this patient group. We have previously covered the approval of postoperative atezolizumab in MMR-deficient colon cancer and which cancers respond to preoperative immunotherapy.
- What was approved: Dostarlimab 500 mg every 3 weeks, up to 9 cycles (about 6 months), for adults with previously untreated dMMR/MSI-H stage II–III locally advanced rectal cancer. This is an accelerated approval; continued approval depends on confirmatory data.
- AZUR-1 (154 patients): Clinical complete response lasting 12 months (cCR12) was 47% by independent central review and 68% by investigator assessment. Overall, 71% of patients are being monitored after dostarlimab alone, with no other treatment and no disease progression; 17% underwent surgery.
- MSK study (50 patients): cCR12 93%, objective response 100%; no patient required chemoradiotherapy or surgery. Among 27 patients followed for at least 3 years, one developed a local recurrence.
- In practice: Every rectal cancer should be tested for MMR/MSI at diagnosis. For patients with dMMR tumors, this option should always be discussed before treatment begins. In Türkiye, dostarlimab is licensed, but not for this indication, and it is not reimbursed by SGK.
Why does this matter?
The standard treatment for locally advanced rectal cancer is chemotherapy and chemoradiotherapy, followed by surgical removal of the rectum. This approach controls the cancer effectively, but it can come at a heavy price: a permanent or temporary colostomy (a stool bag on the abdomen), fecal incontinence and frequent bowel movements, sexual dysfunction and lasting problems in sexual life, and infertility and early menopause caused by radiation. Because rectal cancer is increasingly seen at younger ages, enough to lower the screening age to 45, and even in children and adolescents, many patients live with these side effects for decades.
In a small proportion of rectal cancers (about 5–10% according to the manufacturer; lower in some series), the system that repairs copying errors in DNA is defective. These tumors carry a large number of mutations and are more easily recognized as "foreign" by the immune system. As a result, they can respond remarkably well to immunotherapy drugs that target PD-1. In some of these patients, there is an underlying hereditary cause such as Lynch syndrome. Because the same feature is associated with relative resistance to standard chemotherapy, immunotherapy is all the more valuable in this group.
It is not the first approval for dostarlimab, but it is the first immunotherapy approval for curative-intent treatment of rectal cancer:
- 2021: Dostarlimab received accelerated approval for dMMR endometrial cancer progressing after platinum therapy and later for advanced dMMR solid tumors (tumor-agnostic). These approvals covered metastatic or unresectable disease.
- 2023–2024: Based on the RUBY trial, first-line approval in combination with chemotherapy followed, first for dMMR and then for all advanced or recurrent endometrial cancers.
- 2022 and 2025: The study by Andrea Cercek and colleagues at Memorial Sloan Kettering (MSK), published in NEJM, reported a clinical complete response in every patient with dMMR rectal cancer treated with dostarlimab and drew worldwide attention.
- October 2026: The first immunotherapy approval for stage II–III dMMR/MSI-H rectal cancer. Unlike the earlier approvals, the disease is at an early, curable stage, and the goal is organ preservation. GSK's "first and only" claim applies to this indication; other immunotherapies are also being studied in this setting.
Who is a candidate for dostarlimab in rectal cancer?
According to the FDA approval, dostarlimab is indicated for adults with previously untreated stage II or III locally advanced rectal cancer whose tumors are MSI-H or dMMR. The drug is given intravenously every 3 weeks for up to 9 cycles. Patients with a complete response are monitored with frequent endoscopy and MRI instead of undergoing surgery.
How was AZUR-1 designed?
| Feature | AZUR-1 (basis for approval) | MSK study (supportive) |
|---|---|---|
| Design | Multicenter, single-arm, open-label Phase 2 (NCT05723562); sponsored by GSK | Investigator-initiated, single-arm Phase 2 (NCT04165772) |
| Number of patients | 154 | 50 (rectal) |
| Disease | Previously untreated, dMMR/MSI-H, stage II–III locally advanced rectal cancer | |
| Treatment | Dostarlimab 500 mg intravenously every 3 weeks, 9 cycles (about 6 months) | |
| Primary endpoint | Clinical complete response lasting 12 months (cCR12) by independent central review | cCR12 and objective response |
| Median follow-up | 26.3 months | 27 patients followed for at least 3 years |
In AZUR-1, response was assessed with endoscopy, rectal MRI and chest-abdomen-pelvis CT at weeks 6 and 12 of treatment and about 3 weeks after treatment ended. Patients with a clinical complete response entered non-operative management: comprehensive check-ups every 4 months for the first 2 years, then every 6 months. Patients without a complete response, or whose disease recurred or progressed, were referred for standard treatment.
Results
Independent and investigator assessments differ
Among the 116 patients evaluable by independent central review, the cCR12 rate was 47% (54 patients; 95% CI 37–56%). The FDA text lists this confidence interval as 27–56%; the 37–56% given in the GSK announcement is the mathematically consistent value. In addition, 38 patients (33%) had achieved a clinical complete response but had not yet completed 12 months of follow-up at the data cutoff, and 44 patients (38%) had a near-complete response. Some of these percentages may cover the same patients at different time points and should not be added together. Among the 144 patients evaluated by investigators, the cCR12 rate was 68% (98 patients; 95% CI 60–76%). This difference largely reflects data that are not yet mature and the stricter criteria of the independent review.
AZUR-1: response rates by who assessed them
Percent. Single-arm study, no control group. Colored bar: independent central review; gray bar: investigator assessment.
By independent review, another 38 patients (33%) had achieved a clinical complete response but had not yet completed 12 months of follow-up. The cCR12 rate is expected to rise as the data mature. The comparison is between two assessment methods within the same study.
At a median follow-up of 26.3 months, no patient who achieved cCR12, a clinical complete response or a near-complete response had disease progression. Of the 15 patients who underwent surgery after dostarlimab alone because imaging suggested an incomplete response, 12 had no viable tumor in the surgical specimen (pathological complete response). This suggests that imaging and endoscopy can sometimes underestimate a complete response, meaning some patients may have undergone unnecessary surgery.
Where did patients end up?
AZUR-1: status of 154 patients after treatment
Percent. Single-arm study; all patients received dostarlimab.
Patient numbers: 110, 26, 13, 4 and 1. Of the 15 patients who underwent surgery after dostarlimab alone because of an incomplete response on imaging, 12 had no viable tumor in the surgical specimen.
In absolute numbers: 110 of 154 patients were treated with dostarlimab alone, needed no other treatment, and had no disease progression. For these patients, the rectum was preserved and the long-term side effects of chemoradiotherapy and surgery were avoided. Twenty-six patients underwent surgery, 13 received additional drug therapy or radiation, and only 1 patient had disease progression without receiving other treatment.
The MSK study: smaller, with longer follow-up
In reviewing the application, the FDA also examined 50 patients with rectal cancer from the investigator-initiated study at MSK. In this study, the cCR12 rate was 93% (95% CI 82–99%) and the objective response rate was 100%. No patient received chemoradiotherapy or rectal surgery. Among 27 patients followed for at least 3 years, one developed a local recurrence that was treated with lymph node surgery; one patient withdrew from the study, and one patient passed away from a cause unrelated to the disease under study. An update published in NEJM in 2025 reported a clinical complete response in all 49 patients in the rectal cohort, with 92% of patients disease-free at 2 years.
12-month clinical complete response: two studies
Percent. Colored bars: dostarlimab; two different single-arm studies, no control group.
The MSK study had longer follow-up and patient selection at a single center; AZUR-1 data are not yet mature. Comparisons across different studies are indirect; patient populations, prior treatments and follow-up differ.
Figure 1 · Treatment pathway with dostarlimab in dMMR/MSI-H locally advanced rectal cancer (based on the AZUR-1 design)
Simplified; treatment decisions are made by a multidisciplinary tumor board.
Side effects
Dostarlimab is an immunotherapy drug that targets PD-1, and its side effects are consistent with the known profile of this drug class. According to GSK's announcement, 20% of patients in AZUR-1 had serious adverse reactions; the most common side effects were fatigue (32%), rash (22%), diarrhea (18%) and itching (17%). The rate of permanent discontinuation due to adverse reactions was 3%.
Most common side effects with dostarlimab (AZUR-1)
Percent. From the GSK announcement; single-arm study, no comparison group.
Rates of grade 3 or higher side effects and details of immune-mediated adverse reactions will become clearer when the full data are presented at ESMO 2026.
Warnings in the prescribing information include immune-mediated adverse reactions, which occur when the immune system attacks the body's own organs (thyroid, liver, bowel, lungs, kidneys, skin, pituitary and adrenal glands), infusion reactions, a risk of complications with subsequent allogeneic stem cell transplantation, and a risk of harm to the fetus during pregnancy. Some of these side effects, such as thyroid or pituitary insufficiency, may require lifelong hormone replacement. This risk should always be discussed with patients receiving curative-intent treatment, most of whom are young and otherwise healthy.
How should the results be interpreted?
Strengths
- Consistently high complete response rates in two independent studies with different patient groups.
- The rectum is preserved in the large majority of patients, avoiding the lasting side effects of chemoradiotherapy and surgery.
- A short, defined treatment course: 9 cycles, about 6 months.
- For patients without a complete response, the path to standard treatment (surgery, chemoradiotherapy) remains open.
Points of caution
- No control group: Both studies were single-arm. Dostarlimab has not been compared with standard treatment (chemoradiotherapy and surgery) for long-term survival.
- Accelerated approval: The approval is based on the rate of durable complete response. Long-term recurrence and survival data are not yet available; continued approval depends on confirmatory data.
- Immature data: The 47% rate by independent review partly reflects that many patients have not yet completed 12 months of follow-up. Full interim data from AZUR-1 will be presented at ESMO on October 25, 2026.
- Close monitoring is essential: Non-operative management requires endoscopy, MRI and CT every 4 months for the first 2 years. It needs an experienced center that can provide this follow-up reliably and a patient who can adhere to it.
- The right test is essential: The approval applies to dMMR/MSI-H status determined by an FDA-authorized test. Immunohistochemistry for MMR proteins and MSI analysis by NGS or PCR can be used; when results are equivocal, using both methods together is recommended.
Other immunotherapies and approaches under study
In dMMR/MSI-H colorectal cancer, immunotherapy was first used in metastatic disease with pembrolizumab and nivolumab; dostarlimab has been approved tumor-agnostically for advanced dMMR solid tumors since 2021. In early-stage colon cancer, short courses of preoperative immunotherapy such as nivolumab-ipilimumab have also shown very high pathological response rates. However, use of these drugs in locally advanced rectal cancer for non-operative management, as with dostarlimab, is not yet approved. In the MSK study, similar durable complete responses were also seen in about 65% of dMMR tumors outside the rectum (stomach, esophagus, biliary tract, urinary tract and gynecologic cancers), suggesting the approach may extend to other organs.
Dostarlimab (Jemperli) was licensed in Türkiye on January 19, 2026; however, the indications in the Turkish prescribing information cover only dMMR/MSI-H endometrial cancer, and the drug is not reimbursed by SGK for any indication. It is among the licensed but non-reimbursed drugs. Use in rectal cancer is currently off-label; off-label use authorization must be obtained from TİTCK, and the cost usually falls on the patient. Some patients pursue legal routes for non-reimbursed drugs. SGK's immunotherapy reimbursement criteria include no provision for locally advanced rectal cancer. MMR immunohistochemistry is routinely available at many centers in Türkiye; requesting this test at diagnosis is critical for directing eligible patients to the right treatment. For the access pathway of newly approved drugs in Türkiye, see our access map; for eligible patients, clinical trials are also an option. If needed, a second opinion can be sought.
Practical tips for patients and families
- Rectal cancer is usually diagnosed from a biopsy taken during colonoscopy. If you have been diagnosed, ask whether MMR/MSI testing has been done on the biopsy before starting treatment.
- If the result is dMMR/MSI-H, discuss the immunotherapy option with your oncologist before chemoradiotherapy or surgery.
- If you choose non-operative management, do not miss any check-ups; detecting recurrence early is the foundation of this approach's safety.
- If dMMR is found, seek genetic counseling for Lynch syndrome; this may also matter for your family members.
- During immunotherapy, report any new symptoms such as diarrhea, shortness of breath, extreme fatigue, skin rash or jaundice to your care team right away.
Frequently asked questions
- Can dostarlimab help avoid surgery in rectal cancer?
- It may be possible in dMMR/MSI-H stage II–III rectal cancer. In the AZUR-1 trial, 71% of patients are being monitored after dostarlimab alone, without surgery, radiation or chemotherapy. If a complete response is not achieved, patients move on to standard treatment.
- What do dMMR and MSI-H mean?
- They indicate that the system that repairs copying errors in DNA is defective. These tumors carry many mutations and can respond very well to immunotherapy. This feature is found in a small proportion of rectal cancers and is detected with a simple test on the biopsy.
- How long does dostarlimab treatment last?
- 500 mg intravenously every 3 weeks, up to 9 cycles, or about 6 months. Patients with a complete response are monitored with endoscopy, MRI and CT every 4 months for the first 2 years, then every 6 months.
- Can dostarlimab be used for rectal cancer in Türkiye?
- The drug is licensed in Türkiye, but only for endometrial cancer, and it is not reimbursed by SGK. Use in rectal cancer requires off-label use authorization from TİTCK; the cost is usually borne by the patient.
Glossary
- Locally advanced rectal cancer
- Rectal cancer that has spread into the deep layers of the rectal wall or to nearby lymph nodes but not to distant organs (stage II–III).
- dMMR / MSI-H
- Mismatch repair deficient / microsatellite instability-high; a tumor feature indicating that the DNA repair system is defective.
- Clinical complete response (cCR)
- No trace of the tumor remaining on endoscopy, MRI and CT.
- cCR12
- A clinical complete response lasting at least 12 months; the primary endpoint of AZUR-1.
- Pathological complete response
- No viable tumor cells found in the tissue removed at surgery.
- Non-operative management ("watch-and-wait")
- Close follow-up with regular endoscopy and imaging instead of surgery in a patient with a complete response.
- Accelerated approval
- A type of FDA approval granted on the basis of early results, whose continuation depends on confirmatory data.
DROZDOGAN Academy Commentary
This approval formalizes something rare in oncology: better outcomes with less treatment. But it applies only to patients whose tumors carry the right biomarker.
⚡ Why it matters
For patients with dMMR/MSI-H locally advanced rectal cancer, most of them young, treatment can shift from the triple burden of chemotherapy, radiation and surgery to 6 months of immunotherapy. That means avoiding potentially lifelong consequences such as colostomy, fecal incontinence, loss of sexual function and infertility.
✅ Strengths
Consistent results at MSK and in the multicenter AZUR-1 trial; no progression among patients with a complete response at a median follow-up of more than 2 years; and standard treatment remains possible for patients without a complete response.
⚠️ Limitations
Both studies are single-arm, with no long-term recurrence or survival data. The gap between 47% by independent review and 93% at MSK calls for caution regarding patient selection and data maturity. The confidence interval error in the FDA text also makes seeing the full data at ESMO all the more important.
🩺 In practice
Every newly diagnosed rectal cancer should be tested for MMR/MSI before treatment is planned. For patients with stage II–III dMMR/MSI-H disease, dostarlimab should be discussed as the first option at the multidisciplinary tumor board, and follow-up should be carried out by a team experienced in non-operative management. In Türkiye, an off-label application should be planned for access.
❓ Open questions
What will the 5- and 10-year recurrence rates be in patients managed without surgery? Do all patients need 9 cycles, or could shorter treatment be enough? Could tests such as circulating tumor DNA (ctDNA) identify, before surgery, patients who appear to have an incomplete response on imaging but actually have a pathological complete response? Will the same approach extend tumor-agnostically to other dMMR tumors?
Bottom line: In dMMR/MSI-H locally advanced rectal cancer, dostarlimab is a strong candidate to become the new organ-preserving standard of care. Its first prerequisite, however, is MMR/MSI testing for every patient at diagnosis.
- This article was prepared in October 2026.
- Approval details and efficacy data are based on the FDA announcement of October 19, 2026; safety data and AZUR-1 figures are based on the GSK announcement. Full AZUR-1 data have not yet been published in a peer-reviewed journal and will be presented at ESMO on October 25, 2026.
- The FDA announcement gives the confidence interval for cCR12 by independent review as 27–56%; we used the 37–56% value from the GSK announcement, which is mathematically consistent. The FDA text does not state whether the 33% and 38% rates are mutually exclusive.
- The dMMR/MSI-H frequency (5–10%) is taken from the manufacturer's announcement; lower rates in rectal cancer have been reported in some series. Information on licensing and reimbursement in Türkiye is based on SUT and TİTCK records as of October 2026.
- The comparison in chart C4 is between different studies and is indirect. The diagram is derived from the text and contains no new data. The Academy commentary is our own.
References
- U.S. FDA. FDA grants accelerated approval to dostarlimab for locally advanced rectal cancer (October 19, 2026). fda.gov
- GSK / AnaptysBio. Jemperli (dostarlimab) approved in the U.S. as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer (October 19, 2026). globenewswire.com
- Oncology Nursing News. FDA grants accelerated approval to dostarlimab in dMMR rectal cancer (October 2026). oncnursingnews.com
- OncLive. Dostarlimab achieves sustained clinical complete responses in dMMR/MSI-H rectal cancer (July 13, 2026). onclive.com
- Cercek A, et al. PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022;386:2363-2376. PubMed
- Cercek A, et al. Nonoperative management of mismatch repair-deficient tumors. N Engl J Med 2025. doi.org · ascopost.com
- ClinicalTrials.gov. AZUR-1 (NCT05723562). clinicaltrials.gov · MSK study (NCT04165772). clinicaltrials.gov
- ASCO Post. FDA approves dostarlimab-gxly plus chemotherapy for dMMR or MSI-H endometrial cancer (August 2023). ascopost.com
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