Pembrolizumab Shows ‘Modest Activity’ Against Heavily Pretreated Oesophageal Cancer

Patients with metastatic oesophageal cancer that has progressed after two or more lines of systemic treatment may benefit from pembrolizumab therapy

medwireNews: KEYNOTE-180 trial findings suggest that around 10% of patients with heavily pretreated, metastatic cancer of the oesophagus may achieve a partial but durable response to the programmed cell death ligand 1 (PD-L1) inhibitor pembrolizumab. 

The authors of the phase II study say that their findings, published in JAMA Oncology, show “modest activity” and “support pembrolizumab as a valuable treatment option” for this patient population which has few alternative treatments available. 

After a median follow-up of 5.8 months, the objective response rate (ORR) among the 121 patients given pembrolizumab 200 mg every 3 weeks was 9.9% – fully comprised of partial responses – while 20.7% of patients experienced stable disease, giving a disease control rate of 30.6%. 

The ORR differed by tumour histology, at 14.3% for the 63 patients with squamous cell carcinoma and 5.2% for the 58 patients with adenocarcinoma, and by PD-L1 status, at 13.8% for the 58 patients with PD-L1-positive disease and 6.3% for those with PD-L1-negative tumours. 

The median duration of response was unreached at the time of analysis in either histology subgroup and among the PD-L1-positive patients, whereas the median duration was 4.4 months for those with PD-L1-negative tumours.  

Overall, 9.1% of patients were continuing with pembrolizumab treatment at time of reporting, say Manish Shah, from Weill Cornell Medical College in New York, USA, and co-investigators. 

They describe the median overall survival (OS) of 5.8 months – with 6 and 12 month OS rates of 49% and 28%, respectively – as “encouraging” and say this outcome “compares favourably with the historically observed median OS of less than 4 months and a 12-month OS rate of less than 13% in the second-line setting.” 

And the team adds that the estimated 6-month and 9-month progression-free survival rates of 16% and 9%, respectively, suggest “prolonged survival of patients who were alive and whose disease was not progressing after 6 months.” 

The most common grade 1–2 treatment-related adverse events were fatigue (10.7%), rash (7.4%), pruritus (6.6%), hypothryroidism (5.8%), diarrhoea (4.9%) and pneumonitis (4.9%), with grade 3–5 events in 12.4%, namely pneumonitis (2.4%) and diarrhoea (0.8%). Immune-mediated events were reported for 20.7% of patients, including grade 1–2 hypothyroidism (7.4%) and pneumonitis at both grades 1–2 (4.9%) and 3–5 (2.4%). There was one treatment-related death attributed to pneumonitis. 

Nevertheless, just 4.1% of the patients discontinued treatment because of adverse events and there were no new safety signals, the researchers conclude.



Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus. The phase 2 KEYNOTE-180 study . JAMA Oncol; Advance online publication 20 December 2018. doi:10.1001/jamaoncol.2018.5441 

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