Phase II Nivolumab Results Published For Advanced Refractory Oesophageal SCC

Some patients with heavily pretreated advanced squamous cell carcinoma of the oesophagus have shown response to nivolumab

medwireNews: Phase II trial results have raised the possibility of nivolumab therapy for patients with advanced squamous cell carcinoma of the oesophagus that is refractory or intolerant to standard therapies.

“Our results suggest that nivolumab could be a potential treatment option” for this patient population, say Yasuo Hamamoto, from Keio University School of Medicine in Tokyo, Japan, and co-investigators.

The open-label study included 65 Japanese patients who had previously been treated with fluoropyrimidine-based, platinum-based and taxane-based regimens.

After a median of 10.8 months, the phase II study’s primary endpoint of a partial or complete RECIST-measured objective response by central assessment was achieved by 17% of the 64 assessed patients. The investigator-assessed rate of objective response was 22% and the corresponding rates of disease control were 42% and 53%, respectively.

These results suggest “that the ability of nivolumab to reduce tumour burden in oesophageal squamous-cell carcinoma is long-lasting, similar to the findings in other cancer types”, the authors write in The Lancet Oncology.

Safety analysis showed that treatment was discontinued in seven patients because of treatment-related adverse events.

In all, 85% of the 65 patients had an adverse event during treatment with nivolumab 3 mg/kg every 2 weeks, with 26% experiencing grade 3 or 4 events and 17% grade 3 or 4 serious events.

The most common grade 3 or 4 adverse events were grade 4 dyspnoea (2%) and hyponatraemia (2%), and grade 3 lung infection (8%), decreased appetite (3%), elevated blood creatinine phosphokinase (3%) and dehydration (3%).

The researchers admit that the study had limitations that may restrict generalisability of their results, such as the lack of a comparator group – because no third-line strategy has been validated in this population – and inclusion of only Japanese participants.

But an open-label phase III study comparing nivolumab monotherapy with docetaxel or paclitaxel is now underway for patients with unresectable advanced or recurrent oesophageal cancer, they say.

Sylvain Manfredi and Antoine Drouillard, from University Hospital Dijon in France, observe in an accompanying comment that RECIST valuation “might not be suitable” for immune-checkpoint inhibitor trials and that immune-related response evaluation may be required.

“Immune-checkpoint therapy induces new adverse events rarely seen with standard chemotherapy that clinicians will have to learn to manage, such as endocrine disorders (eg, hypothyroidism), interstitial lung disease, pneumonitis, and eosinophilic pneumonia and other less common immune disorders (eg, pemphigoid)”, they add.


Kudo T, Hamamoto Y, Kato K, et al. Nivolumab treatment for oesophageal squamous-cell carcinoma: an open-label, multicentre, phase 2 trial.Lancet Oncol; Advance online publication 14 March 2017. DOI:

Manfredi S, Drouillard A. Immune-checkpoint inhibition for digestive cancers. Lancet Oncol; Advance online publication 14 March 2017. DOI:

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