Integrating Checkpoint Inhibitors into Treatment of Patients MSI-High Rectal Cancer

At the 2023 World Congress on Gastrointestinal Cancers, Thierry André, MD, Saint-Antoine Hospital, Paris, France discussed the use of checkpoint inhibitors for patients with MSI-high colorectal cancer.

Transcript:

My name is Thierry André. I am a medical oncologist working in Paris at Saint-Antoine Hospital, and the topic today is MSI-high/dMMR rectal cancer. It's a complex situation because it's a rare situation. It is approximately 2% or 3% of the rectal cancer, a majority is Lynch syndrome. And the therapy is complex because the classical therapy with chemotherapy didn't work well and the place of radiotherapy and chemotherapy is not really clear, because probably the efficacy is a little bit lower compared to the MSS rectal cancer.

We had, at ASCO one year ago now and in New England Journal of Medicine, an incredible publication by Andrea Cercek [MD, Memorial Sloak Kettering Cancer Center, New York] and team from New York, Memorial Sloan Kettering, with 12 patients treated with dostarlimab, the immune checkpoint inhibitor, with 12 patients in complete clinical response, with now a follow-up more than 1 year. And we have actualization of this data with now 32 patients with a short median follow-up of 9 months with a clinical response for 23 patients, and for no need of radiotherapy or chemotherapy.

The situation is very complex because the therapy of rectal cancer is, for MSS, complex with chemotherapy, radiochemotherapy, surgery. For MSI, we have these incredible results. We have surgery because MSI is a prognostic factor of rectal cancer and MSI, especially for stage II and also for stage III with low number of lymph nodes, is better than MSS. And surgery, especially for high-type cancer, it's a possibility. But for high-risk patients, for patients with cancer in the low or medium rectum, it's clear that the wish is to avoid the resection of the rectum, and immune checkpoint inhibitor is really an opportunity.

But we have no options at this time. We don't have a lot of data. It's also some data with other PD-1 compounds with the same kind of results, maybe a little bit less spectacular than was published in New England Journal of Medicine. And really, for clinical practice, it's really complex.

We have right now a phase 2 study to try to confirm the results of Cercek and the US team with these incredible results. It's a study with dostarlimab, sponsored by GSK, with a goal to treat 150 patients with dostarlimab for local rectal cancer to confirm. And it's particular because to randomize against the standard of care is difficult, and we are already in a particular situation where it's good to include patients in trial. We have other data with other immune checkpoint inhibitors. And we don't have a lot of data with a combination of anti-PD-1, anti-CTLA4. And it's difficult to know the best duration of therapy. We don't have a lot of data.

We have a lot of questions. We have the possibility to have complete response with 6 months of dostarlimab. We need to have a lot of clinical trial to try to have options, to have the opportunity to treat patients by immune checkpoint inhibitor in this rare situation.

Thank you very much for your attention.

Source:

André T. How to Integrate CPIs in MSI-High Rectal Cancer. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain

Cercek A, Lumish M, Sinopoli J, et al. PD-L1 blockade in mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med. 2022;386:2363-7376. doi:10.1056/NEJMoa2201445