Findings of three studies important to Esophageal Cancer patients were presented at the 2020 ESMO (European Society of Medical Oncology) Virtual Congress on September 21 – all showing a significant benefit to Esophageal Cancer patients who have traditionally had very few treatment options.  Only patients with metastatic Esophageal Squamous Cell Carcinoma who have not had success on other therapies currently qualify for immunotherapy under Food and Drug Administration (FDA) rules.  We expect that is likely to change as pharma giants Bristol-Myers Squibb and Merck work to gain approval for their PD-L1 inhibitors Opdivo (nivolumab) and Keytruda (pembrolizumab), respectively.

ECAN has not had access to the data reported at ESMO but published reports show that these therapies have the potential to make a significant difference in outcomes for patients with Esophageal Cancer.

Immunotherapy Opdivo Doubles Time until Recurrence after Chemoradiation and Esophagectomy in EAC and ESCC

The CheckMate-577 study found that patients who received Opdivo (nivolumab) after chemoradiation and esophagectomy experienced a doubling of the time until recurrence compared to patients who received a placebo.  The results were true for patients with both Esophageal Adenocarcinoma and Esophageal Squamous Cell Carcinoma. This is the first time a therapeutic option has significantly prolonged disease-free survival for patients after undergoing chemotherapy and surgery.

“While about 25% to 30% of patients with esophageal or gastroesophageal junction cancer achieve a complete response following chemoradiation therapy and surgery, the remaining 70% to 75% do not, and there is currently no adjuvant (post-surgery) treatment option available for these patients with the potential to improve their outcomes,” said Ronan J. Kelly M.D., MBA, Director, Charles A. Sammons Cancer Center at Baylor University Medical Center. “Adjuvant treatment with nivolumab the CheckMate-577 trial doubled patients’ time without disease recurrence, representing the first adjuvant treatment advancement for these patients with esophageal or gastroesophageal junction cancer.”

Opdivo was well tolerated with an acceptable safety profile when compared to placebo. The majority of patients in the Opdivo arm (89%) were able to receive a relative dose intensity of ≥ 90%. The incidence of any treatment-related adverse events (TRAEs), including any grade and Grade 3-4, was 71% and 13% among patients treated with Opdivo compared to 46% and 6% among patients receiving placebo. Serious TRAEs of any grade and Grade 3-4 occurred in less than 10% of patients treated with Opdivo (any grade in 8%, Grade 3-4 in 5%) compared to 3% and 1% of patients receiving placebo, with a low rate of any grade treatment-related discontinuations in both arms (9% for Opdivo vs. 3% in placebo).

“These results make esophageal and gastroesophageal junction cancer the second cancer type – following melanoma – where Opdivo has demonstrated a benefit Adin the adjuvant setting, indicating the potential for Opdivo to become a new standard of care for these patients,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol Myers Squibb. “This advancement showcases our commitment to evaluating our therapies in earlier stages of disease where we may be able to have a greater impact on preventing disease recurrence and improving patient outcomes. We look forward to discussing these encouraging results from CheckMate-577 with global health authorities in the coming months.”
Read Bristol-Myers Squibb’s New Release about CheckMate-577.

Keytruda Plus Chemo Reduces Risk of Death in Untreated Metastatic Patients with ESCC, EAC, and GEJ Cancer

Keynote-590 found that Keytruda (pembrolizumab) plus chemotherapy reduced the risk of death by 27% for patients with untreated metastatic esophageal cancer including patients with Esophageal Squamous Cell Carcinoma (ESCC), Esophageal Adenocarcinoma (EAC), and Gastroesophageal Junction (GEJ) tumors – and regardless of their PD-L1 expression – when compared to chemotherapy alone. Keytruda in combination with chemotherapy also significantly improved progression-free survival, reducing the risk of disease progression or death by 35% or more than a third in all randomized patients.

“These findings for Keytruda in combination with chemotherapy are particularly impressive considering improvement in overall survival was observed across all patient populations – including those patients with esophageal squamous cell carcinoma, adenocarcinoma, and gastroesophageal junction tumors – and regardless of PD-L1 expression,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Our goal is to extend the lives of people living with cancer, and these important findings add to a growing body of survival data for Keytruda in a wide range of cancers.”

Patients with ESCC and/or PD-1 expression of 10 or more had the best results.  Median overall survival compared with the placebo regimen among patients with ESCC and a PD-L1 CPS of 10 or more was 13.9 months vs. 8.8 months; among all those with ESCC was 12.6 months vs. 9.8 months; among those with a PD-L1 CPS of 10 or more was 13.5 months vs. 9.4 months, and among all patients was 12.4 months vs. 9.8 months.

“Esophageal cancer is an aggressive disease that is associated with very poor survival, and there is an urgent need for advances for newly diagnosed, previously untreated patients,” said Dr. Ken Kato, chief, department of Head and Neck Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. “In Keynote-590, with a 27% reduction in the risk of death, the results show Keytruda has the potential to change the current treatment paradigm for the first-line treatment of patients with locally advanced and unresectable or metastatic esophageal or esophagogastric junction cancer. Results also showed a median overall survival of 12.4 months for Keytruda versus 9.8 months for chemotherapy.”
Read Merck’s news release on Keynote-590.

Opdivo Plus Chemo Reduces Risk of  Death in Untreated Metastatic Patients with EAC, GEJ, and Gastric Cancers

In the Checkmate-649 study, patients who were not HER2+ with untreated metastatic Esophageal Adenocarcinoma, Gastric, and Gastroesophageal Junction Cancers received Opdivo (nivolumab) and chemotherapy and were compared with similar patients who received chemotherapy alone. this Phase III trial showed that Opdivo reduced the risk of disease progression or death by 32% for patients with PD-1 Expression of at least 5% when compared to Chemotherapy alone.

“Currently, the first-line standard of care for patients with advanced or metastatic non-HER2 positive gastric or gastroesophageal junction cancer is chemotherapy. While it has been an important treatment option for these patients, chemotherapy alone is associated with a marginal survival benefit of often less than one year from the time a patient’s treatment is initiated,” said Markus Moehler, M.D., Professor of Gastrointestinal Oncology, Johannes-Gutenberg University Medical Center, Mainz. “Innovative treatments are urgently needed for patients around the world who are living with these advanced or metastatic upper gastrointestinal cancers, as there are currently no approved immunotherapy options in the first-line setting.”

The study also demonstrated a benefit when adding Opdivo to chemotherapy for patients with lower or no PD-1 expression.  In the all-randomized population, the median overall survival 13.8 months for patients receiving Opdivoplus chemotherapy compared to 11.6 months for patients receiving chemotherapy alone. In PD-L1 positive patients with CPS ≥ 1, the median overall survival was 14 months for patients receiving Opdivo plus chemotherapy compared to 11.3 months for patients receiving chemotherapy alone.

“CheckMate-649 recently became the first global study in over a decade to demonstrate a significant overall survival benefit over chemotherapy in the first-line setting of non-HER2 positive gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, highlighting the potential of Opdivo plus chemotherapy to become a new standard of care for these patients, regardless of their tumor location,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol Myers Squibb. “These available results of the CheckMate-649 study will be discussed with global health authorities as we strive to bring this important new treatment option to patients in need.”
Read Bristol-Myers Squibb’s new release about Checkmate-649.