Pembrolizumab improves on chemo in MSI-H/dMMR mCRC

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Published: 11 Jun 2021
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Prof Thierry André - Sorbonne University and Saint-Antoine Hospital, Paris, France

Prof Thierry André speaks to ecancer in an online interview for the virtual ASCO 2021 meeting about the final overall survival results for the KN177 study.

He explains that the phase III study looked at pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC).

Prof André says that the data confirms pembrolizumab as a new standard-of-care in the first-line for these patients.


My name is Thierry André, I work in Paris in Saint-Antoine Hospital – I’m a medical oncologist. It’s a pleasure for me to have a short summary of the KEYNOTE-177 I presented at ASCO two days ago and one year ago in the plenary session for the first part.

This study was a randomisation for MSI high/deficient mismatch repair metastatic colorectal cancer between chemotherapy, FOLFOX or FOLFIRI plus bevacizumab or cetuximab, versus pembrolizumab. It’s a phase III with more than 300 patients. It was presented at ASCO in the plenary last year for the primary objective. The primary objective was PFS by blinded independent review for the RECIST 1.1 criteria, the PFS by RECIST 1.1. This primary endpoint was met with a doubled PFS – 16 versus 8 months, 16 for pembrolizumab and 8 months for chemotherapy – with a less toxic regimen – 22% of grade 3/4  for pembrolizumab versus 66% for chemotherapy; a different toxicity profile – immunotoxicity for pembrolizumab and more classical for chemotherapy plus or minus targeted therapy; better quality of life – it’s a paper published in Lancet Oncology – and a more convenient schedule for the patient – 30 minute infusion every three weeks for pembrolizumab – against a more difficult schedule with 5FU – 48 infusion with out hospital for the chemotherapy arm. All these data are published in The New England Journal of Medicine at the end of the year.

The oral presentation at ASCO was the second primary endpoint, it was overall survival. The statistical plan was to have this analysis at 190 events or one year after PFS. At the cut-off for this analysis we have 140 events and the analysis was done one year after the PFS analysis. For that we need a p-value stronger than the first one for PFS, for OS it was a p-value of 0.225 and results are improvement in overall survival in this trial. It is a median OS not reached for pembrolizumab versus a median OS of 36.7 months for chemotherapy first line. The hazard ratio is 0.74 with a p-value at 0.359, not significant but with 60% of patients with crossover, it was allowed in the protocol with pembrolizumab, it was 38% in the protocol with pembrolizumab and it is 22% with other immuno-oncology. It is a very high rate of crossover for immuno-oncology in a population where we know immuno-oncology works well because we have now a lot of data to see the data in advanced line with amazing results. For this reason these results, despite a non-significant p-value, confirm the fact that pembrolizumab is the new standard of care for metastatic colorectal cancer MSI high.

The approval of the FDA and the EMA is there right now and the important thing also is we have a little rate of progressive disease at the beginning of the curve, probably because we have some patients resistant to immuno-oncology, but also because we have some sort of progression because it was RECIST 1.1 criteria and also some misdiagnosed MSI high because it was four years ago and the diagnosis is sometimes difficult and it’s possible to have some error. For all these reasons it’s a question we have to better understand how to manage this new therapy in MSI high metastatic colorectal cancer. But it’s really a new step, a revolution, a change of paradigm in 5% of metastatic colorectal cancer and it was a pleasure to have the honour to present this trial. Thank you very much for your attention.