Both Single and Dual Immunotherapy Regimens Offer Improved Overall Survival for Select Patients With Advanced Esophageal Cancer

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For immediate release
June 3, 2021

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Rachel Cagan
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ASCO Perspective
“Certain patients with advanced esophageal cancer, who currently have few treatment options, now stand to gain from immunotherapy. The dual immunotherapy combination of nivolumab and ipilimumab is the first chemotherapy-free first-line treatment showing benefit for these patients,” said ASCO Chief Medical Officer and Executive Vice President Julie R. Gralow, MD, FACP, FASCO.

ALEXANDRIA, Va. — Compared to standard of care chemotherapy, both a dual immunotherapy regimen and a single immunotherapy agent added to chemotherapy extends overall survival (OS) for patients with advanced esophageal squamous cell carcinoma (ESCC), particularly those positive for the immune checkpoint protein PD-L1, according to data from a phase III trial to be presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

Study at a Glance

Focus

To determine survival among patients with ESCC treated with nivolumab (Opdivo) plus chemotherapy, nivolumab plus ipilimumab (Yervoy), or chemotherapy alone.

Population

970 patients with previously untreated, unresectable advanced, recurrent or metastatic ESCC

Findings

  • OS was significantly better among patients with PD-L1 ≥ 1% who received nivolumab plus chemotherapy and nivolumab plus ipilimumab compared to chemotherapy alone —15.4 and 13.7 months respectively compared with 9.1 months.
  • OS was significantly better among all randomized patients with both nivolumab plus chemotherapy and nivolumab plus ipilimumab compared with chemotherapy alone —13.2, 12.8, and 10.7 months, respectively.
  • The time to disease progression (progression-free survival, PFS) with nivolumab plus chemotherapy was significantly better than with chemotherapy alone in patients with PD-L1 ≥ 1%.
  • Adverse events (AE) and serious AEs (≥ grade 3) were comparable between the three groups. Discontinuations, due to any component of a regimen, were more likely for patients receiving nivolumab plus chemotherapy.

Significance

Nivolumab with chemotherapy or nivolumab with ipilimumab may ultimately prove to be superior first-line treatments for ESCC.

Key Findings
In the CheckMate 648, nivolumab plus chemotherapy (cisplatin and 5-fluorouracil) and nivolumab plus ipilimumab both significantly improved OS compared with standard chemotherapy. The co-primary endpoint, OS among patients with PD-L1 ≥ 1%, was significantly better for patients who received nivolumab plus chemotherapy and nivolumab plus ipilimumab compared to chemotherapy alone —15.4 and 13.7 months respectively, compared with 9.1 months.

OS was significantly better among all randomized patients with both nivolumab plus chemotherapy and nivolumab plus ipilimumab compared with chemotherapy alone, 13.2, 12.8, and 10.7 months, respectively.

PFS with nivolumab plus chemotherapy was significantly better than with chemotherapy alone in patients with PD-L1 ≥ 1%.

Treatment advances for recurrent or metastatic ESCC or upper GI cancers have been slower than for other cancers. Chemotherapy with cisplatin and 5-fluorouracil is currently the standard of care for initial treatment in patients with advanced ESCC; however, their prognosis remains poor.

Nivolumab is an immunotherapy agent that belongs to a class of therapies known as checkpoint inhibitors that improves immune system response to tumor cells by blocking a protein (PD-L1) on the tumor cell surface. Ipilimumab is also a checkpoint inhibitor; it targets CTLA4, a protein on T-cells, also improving response against cancer cells.

Nivolumab has been shown to improve survival in patients with advanced ESCC that is refractory or intolerant to previous chemotherapy.1 The combination of nivolumab with ipilimumab has demonstrated significant clinical activity across several tumor types, leading investigators to examine the combination for the treatment of ESCC.2

“The clinically meaningful improvements in survival of these two treatment regimens highlight immunotherapy’s impact on cancer care and should bring new therapeutic options to a group of patients that are often diagnosed when disease has already spread,” said lead author Ian Chau, MD, FRCP, a consultant medical oncologist at the Royal Marsden Hospital in Sutton, United Kingdom.

AEs and serious AEs (≥ grade 3) were comparable between the three groups. Discontinuations (due to any component of a regimen) were more likely for patients receiving nivolumab plus chemotherapy.

About the Study
This randomized phase III trial enrolled 970 patients with previously untreated, unresectable advanced, recurrent or metastatic ESCC. Patients were randomly assigned to receive treatment with nivolumab and chemotherapy (5-fluorouracil and cisplatin); nivolumab and ipilimumab; or chemotherapy alone. Patients randomized to the investigational arms were allowed to receive treatment up to 24 months or until disease progression or unacceptable toxicity. 

Primary endpoints were OS and PFS in patients with tumor cell levels of PD-L1 ≥ 1%. Secondary endpoints included OS and PFS in all randomized patients.

Next Steps
Patients will continue to be followed for OS, PFS, and overall response rate.

View the full abstract

View the author disclosures

For your readers:

View the disclosures for the 2021 Cancer Communications Committee: https://www.asco.org/sites/new-www.asco.org/files/content-files/about-asco/pdf/2021-am-news-planning-team-disclosures.pdf  

View the disclosures for Dr. Gralow: https://coi.asco.org/share/CKD-HYVM/Julie%20Gralow 

View the disclosures for Dr. Pierce: https://coi.asco.org/share/Z2M-8YDX/Lori 

ATTRIBUTION TO THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY ANNUAL MEETING IS REQUESTED IN ALL COVERAGE.

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1. Kato K, Cho BC,Takahashi M, et al. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet. 20:1506-1517, 2019.

2. Klein O, Kee D, Markman B, et al. Immunotherapy of Ipilimumab and Nivolumab in Patients with Advanced Neuroendocrine Tumors: A Subgroup Analysis of the CA209-538 Clinical Trial for Rare Cancers. Clin Cancer Res. 26:4454-4459, 2020

Dr. Chau's Embargoed Presscast Presentation

About ASCO: 

Founded in 1964, the American Society of Clinical Oncology, Inc. (the Society) is committed to the principle that knowledge conquers cancer. Together with the Association for Clinical Oncology, ASCO® represents nearly 45,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of high quality and equitable patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. Conquer Cancer, the ASCO Foundation, supports the Society by funding groundbreaking research and education across cancer’s full continuum. Learn more at www.ASCO.org, explore patient education resources at www.Cancer.Net, and follow us on Facebook, Twitter, LinkedIn, Instagram, and YouTube.