Headlines were justifiably made by a recent clinical drug trial at Memorial Sloan Kettering Cancer Center (MSK) in which dostarlimab was used to treat patients with rectal cancer. Remarkably, all patients treated had a complete response.
While this is very encouraging news, it is still too early to declare victory over this disease, or to start prescribing dostarlimab for every person with rectal cancer.
When evaluating reports from clinical drug trials, it is important to keep a few things in mind. For example: Who were the subjects; how big was the study; was the treatment safe and accessible; how meaningful are the reported endpoints; and for how long was this group followed?
For this particular study authored by Dr. Andrea Cercek, we note that the participants were of a very select subpopulation of rectal cancer patients: Although stage 2 and 3 is common, this clinical trial only treated people whose tumors had the “mismatch repair deficient” (MMR-d) profile, which is found in only about 5% of all patients with rectal cancer – many of them with hereditary and early-age cancer syndromes, making the results even less applicable to the larger population.
Also, the study reported on 12 participants, which is a relatively small number when considering the size of trials reliably needed to change practice. But some of the favorable results – that no significant side effects occurred, and that all 12 patients had such complete response that they avoided (for now) the need for chemotherapy, radiation and surgery – are simply extraordinary!
According to the American Cancer Society (ACS), colorectal cancer is the third leading cause of cancer-related deaths for men and women in the U.S., and the ACS estimates that the U.S. will record 106,180 new cases of colon cancer, and 44,850 new cases of rectal cancer, this year. So, any favorable impact, even in a small subgroup, would have big implications for the population.
Beyond the small size of this trial and the terrific results presented by Dr. Cercek, there are a few subtle yet important points which will require future attention. First, does this study’s measurement of complete response – suggesting no indication of any cancer – mean that all the cancer is gone? Dostarlimab – a checkpoint inhibitor drug currently approved to treat endometrial cancer – immunotherapy helps our bodies’ immune system wake up to kill certain cancer cells, but we don’t know if six months of dostarlimab therapy will be enough to kill those cancer cells permanently and actually cure patients in this setting.
Also, the follow-up in this study ranged between 6 and 25 months. We don’t know if this is long enough to declare any of these patients cured; or, if a few cancer cells are hibernating, then will they recur? To better answer some of these questions, we will need clinical trials with more patients and much longer follow-up.
Our Own Study
Of note, White Plains Hospital is involved in a separate clinical trial involving Dostarlimab, with hematologist and oncologist Dr. Daniel Sammartino as our primary investigator. That study involves patients with advanced nonsmall-cell lung cancer, and who have progressed on prior Anti-PD-(L)1 therapy and chemotherapy. PD-(L)1 therapy involves immune system regulators (or “checkpoint inhibitors”), which are being developed as a treatment for several types of cancer. Phase 2 of the trial closed as of April 14, 2022, having randomized 273 patients at 119 sites throughout 16 countries. Nine of those patients were in the U.S., including one at White Plains Hospital. Phase 2 data will be evaluated prior to opening phase 3, during which the number of patients may increase to 750.
What do these different phases mean? As explained by the ACS, Phase 0 involves exploring if and how a drug may work, and Phase 1 involves determining whether the drug is safe to use. A Phase 2 clinical trial – which is what Dr. Cercek’s study is based upon – is conducted to see if the drug succeeds in treating certain types of cancer. Phase 3 compares the safety and effectiveness of the new treatment against the current standard treatment to determine if it is more efficient at battling the disease. If so, it is at this point that the therapy is typically submitted to the FDA for approval.
However, as the ACS notes, while a drug may get that approval after demonstrating that it reduces the risk of cancer reoccurring after treatment, questions may remain over the patient’s longevity and potential side effects. As for the dostarlimab study at White Plains Hospital, we are estimating it could be up to four years before we know its efficacy for lung cancer patients.
In summary, the results from Dr. Cercek’s paper look very promising, and with more data and follow-up time that approach may become the new accepted standard of care. Even before that, it will make us question our current pathways and consider treating some patients with rectal cancer under an entirely new and simpler paradigm. It also makes us wonder about applying these approaches to other similar cancer types.
One thing is for sure: This study published has delivered dramatic results for all 12 patients and their families, as well as for the entire oncology community. This has engaged the nation and hopefully will help to bring more attention to colorectal cancer screening, family history, and cancer research.
Dr. Joshua Raff is the Director of the Digestive Cancer Program at White Plains Hospital, as well as the Assistant Director of its Nationally Accredited Rectal Cancer Program (NAPRC). To make an appointment, call 914-849-7600.