ESCORT Trial Demonstrates Camrelizumab OS Benefit For Advanced Oesophageal Cancer Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: The PD-1 inhibitor camrelizumab significantly improved overall survival (OS) compared with docetaxel or irinotecan in a phase III trial of Chinese patients with advanced or metastatic oesophageal squamous cell carcinoma who had progressed on or were intolerant to first-line chemotherapy. 

Median OS was 8.3 months for the 228 patients who were randomly assigned to receive camrelizumab 200 mg every 2 weeks versus 6.2 months for the 220 participants who instead were given docetaxel 75 mg/m2 every 3 weeks or irinotecan 180 mg/m2 every 2 weeks. 

This gave a significant hazard ratio (HR) of 0.71 in favour of camrelizumab therapy, report Jianming Xu, from the Fifth Medical Center General Hospital of PLA in Beijing, China, and co-investigators of the ESCORT trial. 

Prespecified Max-Combo analysis to account for treatment delay also supported camrelizumab therapy over chemotherapy, with estimated 6-month OS rates of 63% versus 55%, and corresponding 12-month rates of 34% versus 22%. 

And subgroup analysis indicated an OS benefit with camrelizumab regardless of patient age at baseline, sex, ECOG performance status, disease stage, lymph node and organ metastases, and chemotherapy regimen.  

Although patients with higher PD-L1 expression may have derived greater benefit from camrelizumab than those with lower PD-L1 expression, “clinical benefits […] were observed in all PD-L1 expression subgroups”, the investigators emphasize in The Lancet Oncology. 

“This finding is comparable to that observed in ATTRACTION-3 study, and suggests that PD-L1 expression might not be a solid biomarker for outcome prediction for oesophageal squamous cell carcinoma”, they remark. 

Although median progression-free survival (PFS) was 1.9 months for both treatment arms at data cutoff, the team reports that the “Kaplan-Meier curves separated dramatically thereafter”, resulting in a 6-month PFS rate of 22% with camrelizumab versus 4% for chemotherapy. And 10% of camrelizumab-treated patients achieved PFS at 12 months; this rate was not available for chemotherapy-treated patients, due to progression, death or censoring before 1 year.  

“These improvements over chemotherapy were clinically meaningful, and further supported the remarkable activity of PD-1 blockade in patients with advanced oesophageal squamous cell carcinoma”, comment Jianming Xu et al. 

Camrelizumab treatment lasted a median of six cycles versus three docetaxel and four irinotecan cycles; progressive disease was the most common reason for discontinuation in the camrelizumab and chemotherapy arms (65 vs 61%), while treatment-related adverse events (TRAEs) led to discontinuation in 7% and 5%, respectively. 

“Camrelizumab had a manageable safety profile”, the researchers say, with grade 3 or more severe TRAEs occurring in 19% versus 40% of those given chemotherapy. These events included anaemia (3 vs 5%), abnormal liver function (2 vs <1%), diarrhoea (1 vs 4%), asthenia (1 vs 3%), and death from unknown cause (1 vs <1%). 

In addition, immune-related AEs were reported by 89% of the camrelizumab group, most commonly reactive capillary endothelial proliferation (80%), although this mainly occurred at grade 1 (71%) or grade 2 (8%), with just one case at grade 3. Other immune-related AEs included hypothyroidism (19%), skin reactions (9%), hepatitis (8%), pneumonitis (7%) and hyperthyroidism (6%). 

Health-related quality of life, as measured by the EORTC QLQ-C30 scale, showed comparable baseline scores in the camrelizumab and chemotherapy arms. But after 8 weeks of treatment, the PD-1 inhibitor was associated with a significantly lower risk than chemotherapy of decreased global health status, decreased emotional and social functioning, and worsening symptom domains, such as fatigue and pain. 

“The findings from this study suggest that camrelizumab might represent a novel standard second-line treatment option in Chinese patients with advanced oesophageal squamous cell carcinoma”, the ESCORT investigators conclude. 

Reference  

Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol; Advance online publication 13 May 2020. https://doi.org/10.1016/S1470-2045(20)30110-8