Keytruda Combo Shown to Extend Survival in Advanced Esophageal, GEJ Cancers

Keytruda Combo Shown to Extend Survival in Advanced Esophageal, GEJ Cancers
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Adding Keytruda (pembrolizumab) to standard first-line chemotherapy significantly extends the survival of people with locally advanced or metastatic esophageal and gastroesophageal junction (GEJ) cancer, and also significantly lowers their risk of disease progression or death, according to interim data from a Phase 3 trial.

Notably, these benefits were seen across multiple patient subgroups, regardless of PD-L1 status and cancer subtype. The combination also increased the proportion of responders in the overall population enrolled in the KEYNOTE-590 Phase 3 trial (NCT03189719).

With these findings, Keytruda has now become the first anti-PD-1 immunotherapy that, when used in combination with chemo, increases overall survival, delays disease progression, and increases the response rates of these patients, regardless of the PD-L1 levels in their tumors.

Data from this pivotal trial were presented as a late-breaking abstract, titled “Pembrolizumab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced esophageal cancer: The phase 3 KEYNOTE-590 study,” at the recent European Society for Medical Oncology (ESMO) Virtual Congress 2020, held online.

“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,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development, and chief medical officer, Merck Research Laboratories, said in a press release.

“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,” Baynes added.

Developed and marketed by Merck (known as MSD outside the U.S. and Canada), Keytruda is an immune checkpoint inhibitor approved in the U.S. and Europe for the treatment of different types of cancer.

The therapy works by blocking the activity of a protein receptor found on the surface of immune cells, called PD-1. By preventing PD-1 from interacting with its ligands PD-L1 and PD-L2, which are produced by cancer cells, Keytruda enhances immune cells’ ability to recognize and eliminate malignant cells.

KEYNOTE-590 is investigating whether the addition of Keytruda to platinum-based chemotherapy would be superior to chemo alone at increasing overall survival, delaying disease progression or death, and increasing response rates in patients with advanced esophageal and GEJ cancer.

During the study, 749 patients were randomly assigned to receive first-line therapy with Keytruda, or a placebo, given in combination with chemo (cisplatin plus fluorouracil). Treatment was given for up to two years, until disease progression, unacceptable toxicity, or withdrawal, whichever occurred first.

Interim data from KEYNOTE-590 presented at the ESMO Congress showed that, when given in combination with chemo, Keytruda prolonged the time patients lived from a median of 9.8 to 12.4 months, lowering the risk of death by 27% compared with chemo alone.

These survival benefits were seen in several sub-groups of patients, including those with esophageal squamous cell carcinoma (ESCC) whose tumors contained high levels of PD-L1, in ESCC patients regardless of PD-L1 levels, and in all patients whose tumors expressed PD-L1.

“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 Ken Kato, chief of the department of head and neck medical oncology at the National Cancer Center Hospital in Tokyo.

“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 [inoperable] or metastatic esophageal or esophagogastric junction cancer,” Kato said.

In the overall population, the combination therapy also prolonged the time patients lived without showing signs of disease progression, from a median of 5.8 to 6.3 months, lowering the risk of disease progression or death by 35% compared with chemo alone. Again, these benefits were also seen across patient subgroups, including in all ESCC patients, and in all whose tumors expressed PD-L1.

The percentage of patients who responded to treatment also was higher among those on the combo therapy compared with chemo alone (45.0% vs 29.3%). Responses also lasted longer (median of 8.3 vs 6.0 months).

The incidence of severe (grade 3), life-threatening (grade 4), and fatal (grade 5) adverse events was similar in both treatment groups: 72% in those receiving the combo therapy, and 68% in those treated with chemo alone.

However, the proportion of patients who discontinued treatment due to unwanted side effects was higher in the Keytruda group (19% vs. 12%).

Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Joana holds a BSc in Biology, a MSc in Evolutionary and Developmental Biology and a PhD in Biomedical Sciences from Universidade de Lisboa, Portugal. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells — cells that made up the lining of blood vessels — found in the umbilical cord of newborns.
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