Patients With Esophageal Squamous Cell Carcinoma Respond to Camrelizumab/Apatinib Combo in Second-Line Setting

Data presented at the 2021 Gastrointestinal Cancers Symposium shows promise for the combination of camrelizumab plus apatinib for previously treated patients with esophageal squamous cell carcinoma.

Results of a single-arm, open-label phase 2 study revealed positive clinical results coupled with an acceptable safety profile for camrelizumab (SHR-1210) plus apatinib (Rivoceranib) as therapy in the second-line setting for patients with esophageal squamous cell carcinoma (ESCC).

This study (NCT03736863), whose data were presented during the 2021 Gastrointestinal Cancers Symposium, was the first to explore the combination of a PD-1 inhibitor with an anti-angiogenesis inhibitor as second-line treatment for patients with advanced ESCC.

The anti–PD-1 monoclonal antibody camrelizumab induced significant improvements in overall survival (OS) and objective response rate (ORR) compared with chemotherapy in the randomized phase 3 ESCORT study of Chinese patients with advanced ESCC, but the absolute long-term survival benefit from PD-1 inhibitors remains limited. New treatment options that are effective in this patient population are needed, which led to the rationale for this study. The trial aimed to evaluate the safety and efficacy of camrelizumab in combination with the VEGFR2 inhibitor apatinib in the second-line setting.

The trial, which remains ongoing, is enrolling patients with unresectable locally advanced, locally recurrent, or metastatic ESCC across China. To be included in the study, patients must have an ECOG performance status of 0 or 1, be aged 18 to 75 years, and have progressed on or were intolerant to frontline chemotherapy. Camrelizumab was administered at 200 mg intravenously every 2 weeks, and apatinib was given at 250 mg orally daily in 4-week cycles. The primary end point is investigator-assessed ORR, and secondary end points include OS, progression-free survival (PFS), and disease control rate (DCR).

With a data cutoff date of November 16, 2020, a total of 46 patients had been enrolled from 9 sites and all were included in the full analysis set, as well as the safety analysis set. Thirty patients were evaluated in the per-protocol analysis set. The majority of patients were male (n = 38) and had an ECOG performance status of 1 (n = 34). The median age was 63 (range, 48-72) and metastatic sites included lymph nodes in 35 patients, lung in 9, and liver in 8. Forty-six patients had undergone prior chemotherapy, 33 had undergone surgery, and 17 received radiotherapy.

The ORR among 30 evaluable patients was 43.3%, with 4 patients achieving a complete response (CR) with camrelizumab, 9 achieving a partial response (PR), and 15 reaching stable disease (SD). After confirmation, 3 patients had a CR and 7 had a PR for an ORR of 33.3%. Patients who had a response to treatment demonstrated better tumor shrinkage than those who did not respond. The DCR was 93.3%.

The median PFS was 4.07 months with the combination (95% CI, 3.75-not available). The median 3-month OS rate was 82.2%, the 6-month rate was 67.6%, and the 9-month OS rate was 61.5%.

Overall, 33 patients (71.7%) experienced treatment-emergent adverse events (TEAEs), and these events were grade 3 or higher in 23 patients. The most common grade 3 or higher TEAEs included elevated aspartate aminotransferase in 7 patients (15.2%), elevated alanine transaminase in 5 (10.9%), elevated glutamyltransferase in 4 (8.7%), hemorrhage in 3 (6.5%), and increased total bilirubin, increased direct bilirubin, and esophageal fistula in 2 patients each (4.4%).

Eleven patients temporarily discontinued treatment or had a reduced dose of camrelizumab due to TEAEs.

In terms of any-grade immune-related AEs, 4 patients (8.7%) had thyroid function abnormalities, 2 (4.3%) had reactive capillary endothelial proliferation (RCEP), and 1 (2.2%) had pneumonitis. The only grade 3 or higher immune-related event was RCEP, which occurred in 1 patient (2.2%).

Patients received treatment until disease progression, unacceptable toxicity, patient withdrawal from the study, or investigator decision. Tumor response was evaluated every 2 cycles for the first 12 cycles of treatment, and then every 3 cycles thereafter by RECIST 1.1. AEs were assessed continuously for up to 90 days following the last dose of treatment.

Further randomized phase 3 clinical trials are warranted to further understand the efficacy and safety of camrelizumab plus apatinib in this patient population.


Wang F, Wang J, Wu T, et al. Camrelizumab in combination with apatinib as second-line treatment for advanced esophageal squamous cell carcinoma: A single-arm, open-label, phase II study. J Clin Oncol. 2021;39(suppl 3):215.

Related Videos
An expert from Weill Cornell Medicine highlights key clinical data indicating the benefits of radium-223 in the treatment of patients with metastatic castration-resistant prostate cancer.
The risk of radionuclide exposure to the public reflects one reason urologists need to collaborate with radiation oncologists when administering radiopharmaceuticals to patients with prostate cancer.
Switching out beta emitters for alpha emitters, including radium-223, is one way to improve radiopharmaceutical treatment of prostate cancer, according to an expert from Weill Cornell Medicine.
Data demonstrate the feasibility of automated glomerular filtration rate prediction to decide between partial nephrectomy and radical nephrectomy in kidney cancer, according to an expert from the Cleveland Clinic.
Early phase trials investigating cellular therapies, bispecific antibodies, and antibody-drug conjugates for refractory kidney cancer may uncover strategies to overcome resistance mechanisms.
Increasing cancer antigen presentation as well as working with tumor cells in and delivering novel cells to the microenvironment may help in overcoming mechanisms of immune checkpoint inhibitor resistance in refractory renal cell carcinoma.
Lenvatinib plus pembrolizumab appears to be the best option for patients with refractory metastatic renal cell carcinoma who are progressing on immunotherapy combinations or are lenvatinib naïve.
Ipilimumab monotherapy does not appear effective in driving complete responses in refractory renal cell carcinoma despite yielding some progression-free survival intervals, according to an expert from the University of Texas Southwestern Medical Center.
An expert from the University of Texas Southwestern Medical Center discusses several phase 3 clinical trials supporting the use of various single-agent and combination immunotherapy regimens for advanced kidney cancer.
Shilpa Gupta, MD, shares the current standard of care for muscle-invasive bladder cancer and highlights other options that may be suitable for some patients.
Related Content