Camrelizumab in combination with chemotherapy demonstrated improved overall survival and progression-free survival and a manageable safety profile as frontline therapy compared with placebo plus chemotherapy in patients with advanced or metastatic esophageal squamous cell carcinoma.
Camrelizumab in combination with chemotherapy demonstrated improved overall survival (OS) and progression-free survival (PFS) and a manageable safety profile as frontline therapy compared with placebo plus chemotherapy in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC), according to findings from the ongoing phase 3 ESCORT-1st trial (NCT03691090) that were presented virtually during the 2021 ASCO Annual Meeting.1
At a median follow-up of 10.8 months (interquartile range, 7.3-14.3), the median OS with camrelizumab plus chemotherapy (n = 298) was 15.3 months (95% CI, 12.8-17.3) vs 12.0 months (95% CI, 11.0-13.3) with placebo plus chemotherapy (n = 298; HR, 0.70; 95% CI, 0.56-0.88; P = .001).
The median PFS by independent review was 6.9 months (95% CI, 5.8-7.4) with camrelizumab/chemotherapy vs 5.6 months (95% CI, 5.5-5.7) with placebo/chemotherapy (HR, 0.56; 95% CI, 0.46-0.68; P < .001).
Notably, the OS and PFS benefits observed with the addition of camrelizumab to chemotherapy were maintained across nearly all analyzed subgroups, irrespective of the presence of liver metastases or PD-L1 expression level.
“Novel drugs and strategies are required to improve clinical outcomes of patients with [advanced or metastatic ESCC],” lead study author Rui-hua Xu, MD, PhD, a professor of medical oncology, president of the Sun Yat-sen University Cancer Center, and director of the State Key Laboratory of Oncology in South China, said during a presentation of the data. “This combination strategy has the potential to become a novel, standard, first-line treatment in this population.”
ESCC represents the most dominant histological subtype of esophageal cancer in Asia. The disease is particularly common in China where ESCC comprises 90% of all esophageal cancers. Moreover, the incidence in China accounts for more than half of all ESCC cases globally.
Currently, doublet chemotherapy with paclitaxel and cisplatin is the standard treatment for patients with ESCC in China; however, prognosis remains poor and median OS does not typically extend beyond 13 months, Xu explained.
Camrelizumab is a humanized anti–PD-1 monoclonal antibody that demonstrated promising antitumor activity as second-line therapy for patients with advanced or metastatic ESCC. Findings from the phase 3 ESCORT trial (NCT03099382) demonstrated improved OS, overall response rate (ORR), and duration of response (DOR) with camrelizumab vs chemotherapy in this setting.2
Based on these findings, China’s National Medical Products Administration approved camrelizumab for use as second-line treatment in patients with advanced or metastatic ESCC.
“The combination of immunotherapy with cytotoxic agents has shown encouraging antitumor activity in multiple tumor types, but [we are] lacking clinical evidence in esophageal carcinoma,” said Xu.
To be eligible for enrollment, patients had to have treatment-naïve, histologically or cytologically confirmed, advanced or metastatic ESCC with at least 1 measurable lesion and an ECOG performance status (PS) of 0 or 1.
Patients were randomized 1:1 to receive 200 mg or intravenous camrelizumab every 3 weeks plus 175 mg/m2 of paclitaxel and 75 mg/m2 of cisplatin every 3 weeks for 6 or fewer cycles, or placebo plus chemotherapy. Patients continued on therapy until disease progression, unacceptable toxicity, withdrawal of consent, death, or initiation of new antitumor therapy for a maximum of 2 years.
Patients were stratified by the presence of liver metastases and previous radical chemoradiation therapy.
PFS by independent review and OS served as co-primary end points of the study; PFS by investigator assessment, ORR, disease control rate (DCR), DOR, OS rate, safety, and health-related quality of life (HR-QOL) comprised secondary end points.
In total, 751 patients were screened for enrollment and 506 were randomized. In the camrelizumab-containing arm, 298 patients received therapy, 220 discontinued their assigned treatment, and 78 had treatment ongoing at the time of the data cut-off. In the placebo-containing arm, 297 patients received treatment, 270 discontinued their assigned treatment, and 27 had treatment ongoing at the time of the data cut-off.
Baseline patient characteristics were similar between arms. Patients were a median age of 62 years, and the majority were male with an ECOG PS of 1.
About half of patients in each arm had 1 organ with metastases vs 2 or more organs. In both groups, lymph nodes were the most common sites of metastases followed by the lung, liver, and bone.
In the camrelizumab group, 55.7% of patients had 1% or greater PD-L1 expression, 49.3% had 5% or greater PD-L1 expression, and 34.9% had 10% or greater PD-L1 expression. These rates were similar in the placebo group.
In patients who received camrelizumab, previous therapies included surgery (39.9%), antitumor medication (25.2%), and radiotherapy (18.1%); these findings were similar to those in patients who received the placebo-containing regimen.
Additional findings from the study demonstrated that objective responses were confirmed in 72.1% (n = 215; 95% CI, 66.7%-77.2%) of patients with camrelizumab/chemotherapy vs 62.1% (n = 185; 95% CI, 56.3%-67.6%) of patients with placebo/chemotherapy. Rates of disease control were 91.3% (n = 272; 95% CI, 87.5%-94.2%) vs 88.9% (n = 265; 95% CI, 84.8%-92.3%), respectively.
Best overall responses in the camrelizumab-containing arm were comprised of complete responses (CRs; 6.7%, n = 20), partial responses (PRs; 65.4%, n = 195), and stable disease (SD; 19.1%; n = 57). In this arm, 4.7% of patients (n = 14) experienced progressive disease and 4% (n = 12) were not assessable.
Best overall responses in the placebo-containing arm included CRs (3.7%; n = 11), PRs (58.4%; n = 174), and SD (26.8%; n = 80). Five percent of patients (n = 15) developed progressive disease, 0.7% (n = 2) were not evaluable for best response, and 5.4% (n = 16) were not assessable.
Additionally, the median DOR was 7.0 months (95% CI, 6.1-8.9) with camrelizumab/chemotherapy vs 4.6 months (95% CI, 4.3-5.5) with placebo/chemotherapy.
Regarding safety, treatment-related adverse effects (TRAEs) were observed in 99.3% of patients with camrelizumab/chemotherapy vs 97.0% of patients with placebo/chemotherapy. Of these, 63.4% vs 67.7% were grade 3 or higher TRAEs, respectively, and 30.2% vs 23.2% were serious TRAEs, respectively.
TRAEs that led to any treatment interruption occurred in 45.3% of patients who received the camrelizumab-containing regimen vs 23.9% of patients who received the placebo-containing regimen. TRAEs that led to any treatment discontinuation occurred in 12.1% vs 9.4% of patients, respectively. TRAEs that led to death occurred in 3.0% vs 3.7% of patients, respectively.
The incidences of TRAEs were similar between arms; however, reactive cutaneous capillary endothelial proliferation was significantly more common with the camrelizumab-containing regimen vs the placebo-containing regimen. Other common TRAEs that occurred in both arms included anemia, decreased white blood cell count, decreased neutrophil count, nausea, asthenia, alopecia, decreased appetite, vomiting, platelet count decrease, weight loss, increased blood creatinine, increased aspartate aminotransferase, hypoalbuminemia, and hypoesthesia.
“Camrelizumab plus chemotherapy has a manageable safety profile [that is] similar to chemotherapy alone, and no new safety signals were identified,” Xu said.
HR-QOL assessments indicated that patients who received camrelizumab/chemotherapy had a lower risk of global health status deterioration and pain after treatment vs those who received placebo/chemotherapy. Camrelizumab plus chemotherapy also conferred a lower risk of worsening in eating, trouble swallowing saliva, and choking vs placebo plus chemotherapy.
“Based on this trial, we are submitting [a new drug application] to seek approval from the China National Medical Products Administration for camrelizumab plus chemotherapy in the treatment of untreated advanced or metastatic ESCC,” concluded Xu.