Breakthrough Findings for MMRd Rectal Cancer Patients Presented at ASCO 2022

I bet you have seen the breaking news online about colon and rectal (colorectal) cancer this week. A team of researchers, led by Dr. Luis Alberto Diaz and Dr. Andrea Cerek had some exciting results for a subset of rectal cancer patients presented at the 2022 ASCO Annual Meeting. The study was presented during the conference (Abstract LBA5) and simultaneously published in The New England Journal of Medicine.

WHAT DID THE RECTAL CANCER STUDY FIND?

This exploratory clinical trial treated 14 patients with stage II and III MMRd (mismatch repair deficient) rectal cancer for six months with the anti PD-1 monoclonal antibody dostarlimab-gxly. MMRd is an inherited or acquired defect in the mechanism that repairs defects in DNA that can occur as cells divide. Because these defects are not repaired in patients with MMRd cancer, cells in patients with this type of tumor become better targets enhancing the effectiveness of immuno-oncology drugs that target PD-1. All patients treated in the study so far had a complete response (CR) with the drug treatment alone. None have so far required chemotherapy, surgery, or radiation treatments to control their disease. Further follow-up of patients will be necessary to determine if these CRs are long lasting. Patients with MMRd tumors treated with other PD-1 inhibitors for advanced disease have been long-term responders, and it seems realistic to hope that long-term responses will be seen in the study patients as well. This small phase II study (NCT04165772) is ongoing at the Memorial Sloan Kettering Cancer Center (NY), and will ultimately enroll 30 patients. The oncology and advocacy communities are abuzz with talk about the “unprecedented 100% complete response” observed by this investigator team.

WHO DO THE RECTAL CANCER TRIAL RESULTS IMPACT?

About 5% to 10% of all rectal cancers are MMRd, and these tumors are relatively resistant to chemotherapy. The standard of care for patients with localized rectal cancer is the combination of chemotherapy, radiation, and surgery. In the case of the patients in this study, this immunotherapy (anti PD-1 dostarlimab, Jemperli) has spared every one of the study subjects treated so far the need for the three modalities of treatment.

WHAT DOES THIS MEAN FOR RECTAL CANCER PATIENTS?

Since the immunotherapy alone has made the cancer disappear, the researchers have coined a new term: “immunoablative” neoadjuvant therapy – immunotherapy given as the first step in treatment, that can result in the elimination of the cancer. Treatment was given as infusion, every three weeks for a total of six months. It is also remarkable that the majority of these patients had high-risk big bulky tumors, and 94% of the tumors were node-positive on imaging tests.

Median follow-up is currently only 6.8 months, but four patients have been followed for nearly two years, and four who have received even less than six months of the required treatment have achieved a complete response. No disease recurrences were observed. There were no severe side effects (grade 3 or 4 events) observed with this treatment.

IS THIS NEW RECTAL CANCER IMMUNOTHERAPY DRUG APPROVED BY THE FDA?

Yes. Dostarlimab was approved by the FDA in August 2021 for the treatment of patients with MMRd recurrent or advanced solid tumors who have progressed on or following prior therapy and who have no satisfactory treatment options.

“Even though this is a small study whose results are immature, and more testing is needed before the findings can be translated into a change in practice, this study highlights the clinical impact of biomarker-driven therapy for early-stage disease. It also strengthens the argument for universal mismatch repair status and Lynch Syndrome screening just after a CRC diagnosis so that patients like those enrolled in this trial and all patients with MMRd tumors can benefit from individualized therapy. This study also shows how participating in clinical trials can benefit patients with early-stage disease. The alternative standard therapy is often curative at the expense of potential long-term side effects related to chemotherapy, scarring of the pelvis and loss of childbearing potential, as well as the possibility of a permanent colostomy. This approach, if the results are confirmed, holds out the hope of cure without the need for potentially toxic therapy and the need to tolerate long term negative treatment consequences in order to achieve a cure.” 

-Richard Goldberg, MD, professor emeritus at West Virginia University and a Fight CRC Board member

WHAT'S THE BOTTOM LINE FOR RECTAL CANCER PATIENTS?

Even though this is a small study group, and more testing is needed before the findings can become practice changing, this study does highlight the clinical impact of biomarker-driven therapy at early-stage disease for rectal cancer patients, and strengthens the argument for universal mismatch repair status and Lynch Syndrome screening just after a CRC diagnosis.

It also reminds us that participating in clinical trials can lead to breakthroughs that will help treat so many who are walking in your shoes. 

SOURCES:

Abstract: Single agent PD-1 blockade as curative-intent treatment in mismatch repair deficient locally advanced rectal cancer

Published study: PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer

Trial: Study of Induction PD-1 Blockade in Subjects With Locally Advanced Mismatch Repair Deficient Solid Tumor

For more helpful patient tools, please check out Fight CRC's Clinical Trial Finder, Patient Provider Finder, and biomarker resources, as well as our Path to a Cure report.