https://doi.org/10.55788/e6d32a5f
Approximately 10–15% of non-metastatic colon cancers demonstrate dMMR [1]. Patients with stage III dMMR tumours have recurrence rates of 20–40%, despite standard-of-care chemotherapy [2] and high-risk disease (T4- and/or N2-status) is associated with poor survival. Neoadjuvant chemotherapy in patients with dMMR colon cancer leads to a slim pathological response of 5–7% [3]. More promisingly, results from the proof-of-concept NICHE-1 trial (n=32) showed that immune checkpoint inhibition is highly effective in non-metastatic dMMR colon cancers, with 100% pathological responses and 60% pathological complete responses (pCR) [4].
Dr Miriam Chalabi (Netherlands Cancer Institute, the Netherlands) presented the first results of the subsequent (investigator-initiated) NICHE-2 study (EudraCT 2016-002940-17). The study included 112 patients (83 high-risk, stage III) with previously untreated, non-metastatic dMMR colon cancer, who were treated with one cycle nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg), followed by a second cycle nivolumab (3 mg/kg) and subsequent surgery. The primary objectives were safety/feasibility (<2 weeks delay in surgery for 95% of patients) and 3-year disease-free survival. Secondary objectives were response rates assessed in post-treatment specimens. [5].
Grade ≥3 immune-related adverse events were observed in 4 participants and were manageable. All participants underwent surgery, resulting in 100% R0 resection. The median time from the first dose of immunotherapy to surgery was 5.4 weeks and 98% of participants underwent timely surgery. Based on these results, the primary safety endpoint was met.
Major pathological responses (≤10% residual viable tumour or pCR with a residual viable tumour in lymph nodes) were achieved in 95% of participants and 65% of participants achieved pCR. These results agree with the outcomes of the NICHE-1 study (see Figure). At the median follow-up of 13.1 months, none of the participants had disease recurrence.
Dr Chalabi concluded that “with only 4 weeks of neoadjuvant immunotherapy, an unprecedented major pathological response rate was achieved and the treatment was well tolerated. While we are currently acquiring the 3-year disease-free survival data, these data already show that neoadjuvant immunotherapy may have the potential to become standard-of-care for patients with dMMR colon cancer.”
- Eikenboom EL, et al. Clin Gastroenterol Hepatol. 2022;20(3):e496–e507.
- André T, et al. J Clin Oncol. 2015;33(35):4176–4187.
- Seligmann JF, FOxTROT Collaborative Group. J Clin Oncol. 2020;38:15_Suppl, 4013–4013.
- Chalabi M, et al. Nat Med. 2020;26(4):566–576.
- Chalabi M, et al. Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study. Abstract LBA7, ESMO Congress 2022, 09–13 September, Paris, France.
Figure: Pathological tumour regression upon neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer: comparison of NICHE-1 and NICHE-2 [5].

Copyright ©2022 Medicom Medical Publishers
Posted on
Previous Article
« Fruquintinib: a potential new treatment for patients with refractory mCRC Next Article
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel »
« Fruquintinib: a potential new treatment for patients with refractory mCRC Next Article
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel »
Table of Contents: ESMO 2022
Featured articles
Letter from the Editor
Colorectal Cancer
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Breast Cancer
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
Lung Cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Melanoma
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
Gynaecological cancers
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma
Related Articles
November 16, 2022
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
© 2024 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy
HEAD OFFICE
Laarderhoogtweg 25
1101 EB Amsterdam
The Netherlands
T: +31 85 4012 560
E: publishers@medicom-publishers.com