Just a few doses of immunotherapy before surgery for mismatch repair-deficient colon cancer could significantly boost progression-free survival, according to data presented at the recent European Society for Medical Oncology conference in Paris.
Just a few doses of immunotherapy before surgery for mismatch repair-deficient colon cancer could significantly boost progression-free survival, according to data presented at the recent European Society for Medical Oncology conference in Paris.
Conference Twitter lit up when medical oncologist Dr Myriam Chalabi, from the Netherlands Cancer Institute, presented results from the NICHE-2 study at the conference. The study involved 112 patients with non-metastatic deficient mismatch repair colon cancer, who were treated with one dose of immune checkpoint inhibitor ipilimumab and two doses of nivolumab before undergoing surgery.
The cause of the excitement was Chalabi’s slide showing that 97% of patients had a major pathological response to treatment – defined as less than 10% residual viable tumour – and two-thirds showed a complete response to the treatment. At a median of 13 months after treatment – which ranged from one month to 57 months of follow-up – there were no cases of disease recurrence. One commentator said the results raised the prospect of non-operable management of this form of colon cancer.
Deficient mismatch repair – also known as microsatellite instable – colon cancer represents around 15% of patients with non-metastatic colon cancer. It results in a large number of mutations, which may be why immunotherapy is more successful in treating it, said bowel cancer researcher Professor Mark Molloy, from the University of Sydney. “They have a high production of neo-epitopes, which is really what the immune system hones in on when it becomes active,” he said.
Medical oncologist Associate Professor Jeanne Tie, from the Peter MacCallum Cancer Centre – who attended the presentation – said the results weren’t necessarily surprising, given previous data from the earlier NICHE trial and others. However she said the effect of such a small amount of treatment was impressive. “Four weeks of treatment, two doses of immunotherapy, and that is giving you close to 70% of pathological complete response rate,” Professor Tie said.
The previous NICHE trial, the results of which were published in April 2020, involved 40 patients with non-metastatic colon cancer – half with deficient mismatch repair tumours and the other half proficient mismatch repair. They were treated with one dose of ipilimumab and two of nivolumab before surgery. The deficient mismatch repair patients showed a 100% pathological response rate, while the proficient mismatch repair group showed a 27% response rate.
The NICHE-2 study was larger, and did not include a proficient mismatch repair group for comparison. Nearly 90% of those in the study were stage 3, 77% were high-risk stage 3, and 64% had T4 stage tumours. Three patients experienced grade 3-4 immune-related adverse events, including asymptomatic amylase and lipase increases, hepatitis, myositis, and rash, and just over 60% experienced any kind of adverse event.
The greatest treatment responses were seen in patients with low risk stage 3 tumours, all of whom had a major pathological response to treatment and more than three-quarters showed complete pathological response.
The study’s authors said the results suggested that neoadjuvant immunotherapy could become standard of care for this patient group, and “allow further exploration of organ-sparing approaches.”
Professor Molloy described the results as a potential game-changer for a small subset of patients with bowel cancer. “It really opens up the potential there for organ preservation,” he said. “People can be treated with this, they can have medical imaging to see whether the tumour has regressed and potentially go onto this ‘wait and watch’ program.”
Tie noted the absence of a control group and more long-term follow-up meant it was too soon to know how this would change clinical management of patients with deficient mismatch repair colon cancer. On the question of whether this might avoid surgery for some patients, Professor Tie pointed out that around one-third of patients didn’t show a complete response. “What do you do with those – do you do four-monthly colonoscopy?”
She also commented that patients with deficient mismatch repair colon cancer – particularly stage 2 – generally did well with surgery alone and disease-free survival was high for this type of cancer in the earlier stages.
“I think this is great data, very promising, [but] how we should use it, how we move forward, I think still needs to be defined further,” she said.
The three-year follow-up data is expected to be released next year.
