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Organ-Sparing Potentials from the Neoadjuvant Pembrolizumab Treatment in Patients with dMMR/MSI-H Solid Tumours

Findings from a phase II open-label study in patients with localised solid tumours
19 Sep 2021

In a phase II open-label study performed among patients with localised, unresectable or high risk resectable, microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) solid tumours, treatment with neoadjuvant pembrolizumab was safe and resulted in high rates of radiographic and endoscopic responses. The results were presented by Dr. Kaysia Ludford, assistant professor in the Division of Cancer Medicine, MD Anderson Cancer Center in Houston, TX, US during the proffered papers session on translational research at ESMO Congress 2021 (16-21 September).  

Dr. Ludford told the audience that pembrolizumab significantly improves clinical outcomes in patients with advanced/metastatic MSI-H)/dMMR solid tumours. In this study, Dr. Ludford and colleagues evaluated pembrolizumb in the neoadjuvant setting, exploring the potential for an organ-sparing strategy.

Patients included in this single centre study had MSI-H/dMMR non-metastatic solid tumours with localised, unresectable or high-risk resectable (defined as at least 20% recurrence) measurable disease. Pembrolizumab was given at 200 mg dose every 3 weeks for 8 cycles and followed by surgical resection with option to continue pembrolizumab for 18 cycles followed by observation. First restaging was performed at 6 weeks and included baseline and 3-week 70-gene circulating tumour DNA (ctDNA) assessment.

To continue on study, it was required that patients have partial response (PR) or complete response (CR), stable disease (SD) with tumour shrinkage or SD with decline in ctDNA.

The study co-primary endpoints were safety and pathological complete response (pCR). Key secondary endpoints were response rate and organ-sparing at one year for patients who declined surgery.

The researchers enrolled in this study 35 patients between October 2019 and March 2021. Among included patients, 27 had colorectal cancer (CRC) and 8 patients had either endometrial cancer, gastric cancer, meningioma, duodenal cancer, ampullary cancer or pancreatic cancer. Median follow-up was 9 months (range, 0.1 - 17).

Among 32 evaluable patients, best overall response rate was reported in 75% patients with 25% achieving CR and 50% PR, SD was reported in 22% patients and 3% had progressive disease. Complete endoscopic response was seen in 12 of 22 patients (55%) and near response in 4 of 22 (18%).

Among 15 patients (43%) who underwent surgery, pCR was reported in 10.

At time of reporting, non-operative approach was selected by 4patients (11%) with 1-year organ-sparing seen in all four patients. An additional five patients stopped therapy before one year of treatment and experienced a clinical benefit, including one patient with stable disease and four with partial or complete response.

Treatment-related grade 3/4 immune adverse events were seen in 3 patients (9%), in particular transaminitis, diarrhoea and type 1 diabetes.

Baseline ctDNA mutations were present in 20 patients (57%) and at 3 weeks declined in 15 patients (75%), were unchanged in 1 patient, no paired 3-week sample was reported in 1 patient and increased in 3 patients.

Tumour microenvironment immune analysis was ongoing at the time of reporting.

The authors concluded that treatment with neoadjuvant pembrolizumab in patients with dMMR/MSI-H solid tumours is safe and resulted in high rates of radiographic and endoscopic response. These findings have implications for organ-sparing strategies. They also stated that non-operative management of patients with dMMR/MSI-H localised solid tumours should be further investigated.

This study was funded by Merck.


1758O – Ludford K, Raghav K, Murphy MAB, Overman, M et al. Neoadjuvant pembrolizumab in localized/locally advanced solid tumors with mismatch repair deficiency. ESMO Congress 2021 (16-21 September).

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