Bowel cancer is the third most common cancer in Australia.
Around 69% of bowel cancers are located in the colon and 31% in the rectum.
Each year there are 4,919 new rectal cancer cases and 2,815 rectal cancer deaths.
Around 5-10% of rectal cancers are microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). These cancers are relatively resistant to chemotherapy, which forms part of the current standard of care for stage II and III rectal cancer – chemotherapy, radiation and surgery.
In a new phase 2 trial in the United States looking at patients with dMMR stage II or III rectal cancer, a single agent immunotherapy, dostarlimab, was administered via infusion every 3 weeks for 6 months with a view to following up with chemotherapy, radiation and surgery. A total of 12 patients completed treatment with dostarlimab, with follow-up ranging from 6 to 25 months.
All 12 patients had a clinical complete response, with no progression, recurrence or serious side effects reported in the follow-up period. These patients did not require chemotherapy, radiation or surgery following the administration of dostarlimab. While a longer follow up period is needed to assess the duration of the response, the results are promising.
The trial highlights the importance of biomarker-driven therapy in stage II and III disease.
Bowel Cancer Australia Medical Director A/Prof Graham Newstead AM said, “if further trials confirm these encouraging results, for a subgroup of rectal cancer patients, immunotherapy could mean traditional and more intensive therapies such as chemotherapy, radiation and surgery may be omitted, and patients spared from serious side effects and long-term impacts such as pelvic scarring, loss of childbearing potential and permanent colostomy.”
Jemperli (dostarlimab) has been provisionally approved in Australia to treat recurrent or advanced mismatch repair deficient (dMMR) endometrial cancer, a decision based on promising results from preliminary studies.
Update - September 2022
The results from a multi-centre trial on mismatch repair deficient (dMMR) colon cancer patients were presented at the 2022 ESMO Congress in September.
The 112 patients in the NICHE-2 trial had non-metastatic, previously untreated dMMR colon cancer and were treated with neoadjuvant immunotherapy agents Opdivo (nivolumab) and Yervoy (ipilimumab).
Major pathologic responses were achieved in 95% of patients after only four weeks of treatment.
“This stands in stark contrast to data from neoadjuvant chemotherapy in this same patient population [that had] only 7% pathologic responses,” said Myriam Chalabi, a medical oncologist at the Netherlands Cancer Institute.
All patients underwent surgery within six weeks of enrolling in the trial and achieved tumour-free resection margins.
A pathologic complete response was seen in 67% of patients.
The three-year data on disease free survival (DFS) is expected in 2023.