Dostarlimab: Game Changer in Rectal Cancer Treatment?

Mark A. Lewis, MD, director of gastrointestinal oncology at Intermountain Health, discusses the exciting progress of dostarlimab (Jemperli), an immunotherapy drug, in treating rectal cancer.

Early trials, as well as updated data presented at the 2024 American Society of Clinical Oncology Annual Meeting, showed a remarkable 100% complete response rate in patients with mismatch repair–deficient colorectal cancer. This, Lewis explains, could potentially eliminate the need for chemotherapy, radiation, and surgery in this patient population.

Lewis emphasizes the importance of wider adoption of this approach. However, concerns exist about whether the effectiveness of dostarlimab is unique or if other similar agents would work.

Additionally, Lewis highlights the need for more widespread testing for the specific mutation to ensure all eligible patients benefit. Overall, dostarlimab presents a promising new direction in treating rectal cancer, but further research and wider testing to maximize its potential is still needed.

Transcription:

0:09 | So, dostarlimab is a fascinating drug. Of course, it is 1 of many immunotherapies available now in GI cancer. Specifically, it is a PD-1 inhibitor. And I have to say, although we're talking about ASCO 2024, arguably dostarlimab was kind of the belle of the ball 2 years ago at ASCO 2022 when the Memorial Sloan Kettering group led by Andrea Cercek, MD, first announced really remarkable results. What they announced at that meeting was the in locally advanced mismatch repair–deficient rectal cancer, they were seeing in their first dozen or so patients complete clinical responses to upfront immunotherapy. And by upfront, I mean was originally given with neoadjuvant intent. But neoadjuvant implies that surgery is going to follow. And of course, in rectal cancer for years and decades, our paradigm has been one of trimodality therapy. So typically radiation and chemotherapy given preoperatively and then surgery.

1:09 | For a long time, we have been asking the question, well, what if chemo and radiation are enough? Does that actually change the paradigm from TNT, total neoadjuvant therapy, to TDT, total definitive therapy? Because again, adjuvant or neoadjuvant, those are moot points if there is no surgery. But this went one better than that MSKCC study because they showed again, 12 out of 12, 100% complete clinical responses. If memory serves, I think it was on the front page of The New York Times, the same day as plenary in 2022. I know for a fact that my friends and family who are not in medicine knew about it roughly the same time I did. It was a big news story. Dr. Cercek herself has recently been recognized, I think rightly so, as one of the top 100 people in healthcare by Time Magazine.

1:52 | Regardless, the point of this meeting was an update now, 2 years on, not just for those original 12 or so enrollees, but for more enrollees on their trial. Again, the same criteria, mismatch repair–deficient locally advanced rectal cancer getting to dostarlimab for up to 6 months. Still 100%. It is truly remarkable, a 100% clinical complete response rate. What we now have with time is 20 of those patients have what they're calling a sustained clinical response of longer than a year. So this is amazing. This is the new era of not just neoadjuvant, but definitive management in rectal cancer. It doesn't require chemotherapy, doesn't require radiation, doesn't require surgery, which is absolutely amazing.

2:41 | I think that the big question is, is this really special to dostarlimab, not denigrating the investigators would quote any anti-PD-1 agent do in this setting. I think a lot of us wonder about that. And then secondly, I think this just raises the importance of making sure that all the patients who would be eligible for this approach are tested. We are now absolutely in the era where biomarker testing is as important in colorectal cancer as say it is in breast cancer. The reason I use breast cancer as an analogy is that no oncologist I know would ever dream or dare of treating breast cancer without at least trying to establish the ER, PR, and HER2 receptor status. The entire management of breast cancer is predicated on knowing receptors.

3:30 | But we are at that point now, and have been in colorectal cancer, and the reason I have reservations about the generalizability of this study is I know from studying real-world practice, only about 2 thirds of patients with colorectal cancer are even getting tested for mismatch repair deficiency or microsatellite instability. To me, that means we are missing a full third of patients who could benefit, which is just completely unacceptable. We need to change the paradigm, we need to view breast cancer as sort of the high watermark, and then we need to bring the other tumor types, especially in GI up to that level. But do not get me wrong. These are all just my minor critiques. I think this is an incredibly exciting and more mature dataset that the Sloan Kettering investigators have given us.