Immunotherapy in Patients With Early dMMR Rectal Cancer
Status:
Not yet recruiting
Trial end date:
2027-02-01
Target enrollment:
Participant gender:
Summary
Colorectal cancer (CRC) is the third most common cancer (1.8 million cases) and the third
most common cause of cancer-related death (0.8 million deaths) worldwide in 2018, and rectal
cancer accounts for roughly one-third of CRC.
The main curative treatment modality for patients with rectal cancer is surgery, often
combined with chemotherapy and/or radiotherapy (RT). The global recognition of total
mesorectal excision (TME), that decreased locoregional recurrence (LRR) by itself, questioned
the need for radiotherapy (RT) before or after surgery. Several randomized trials have
demonstrated the importance of preoperative RT (short course RT or long course
chemo-radiotherapy (CRT)) in reducing LRR, in patients with high-risk rectal cancer. However,
RT or CRT does not improve overall survival, and in addition neoadjuvant RT/CRT followed by
TME is associated with perioperative morbidity and the risk is increasing with age.
Therefore, ongoing trials are testing other strategies, such as the omission of (C)RT or even
avoidance of surgery.
In May 2022, a presentation with simultaneous NEJM publication showed that 14/14 patients
with dMMR rectal cancer obtained complete response after six months (9 cycles every 3 weeks)
of immunotherapy (dostarlimab). Thus, the investigators have now become confident that
immunotherapy without surgery will be the "new standard", and the investigators will
recommend a W&W strategy in patients with rectal cancer obtaining major tumor shrinkage and
these patients will be followed carefully with clinical and molecular evaluation (which was
not part of the NEJM paper). No patient in the NEJM paper had progressive disease and
therefore the investigators recommend a second cycle of immunotherapy (instead of resection
in unclear cases) and re-evaluation. The investigators are confident that 1 or 2 cycles of
immunotherapy will result in complete radiological, pathological, and molecular response in a
substantial number of patients and this short duration of therapy will reduce toxicity and
especially drug costs.
In conclusion, immunotherapy in patients with dMMR CRC tumors may completely eradicate the
primary cancer and regional lymph nodes leading to a possibility for organ-sparing medical
treatments, and the investigators are confident that this new strategy of 1 or 2 cycles of
immunotherapy will be the future standard of care, and in Denmark the investigators have the
chance to monitor these patients closely with clinical and high-level molecular follow-up.
Phase:
Phase 2
Details
Lead Sponsor:
Odense University Hospital
Collaborators:
Aalborg University Hospital Aarhus University Hospital Bispebjerg Hospital Herlev and Gentofte Hospital Rigshospitalet, Denmark Vejle Hospital Zealand University Hospital