Second-line treatment with Keytruda (pembrolizumab) significantly extends the lives of advanced esophageal cancer and esophagogastric junction carcinoma patients whose tumors are positive for the PD-L1 factor, a Phase 3 clinical trial shows.
Findings from KEYNOTE-181 (NCT02564263), which compared Keytruda to standard chemotherapy, were presented recently at the 2019 Gastrointestinal Cancers Symposium (ASCO GI).
Takashi Kojima, MD, professor at the Department of Gastroenterology and Gastrointestinal Oncology at the National Cancer Center Hospital East in Kashiwa, Japan, gave the oral presentation, “Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase III KEYNOTE-181 study.”
The data will now be submitted to the U.S. Food and Drug Administration (FDA) and other regulatory authorities for review.
“The prognosis for patients diagnosed with esophageal cancer is poor, and for those who experience disease progression, there is no established standard of care, underscoring the need for improved therapies in the second-line setting,” Kojima said in a press release.
Keytruda, developed by Merck (known as MSD outside the United States and Canada), is a PD-1 antibody that blocks the binding of cancer cells’ PD-L1 with the PD-1 receptor in immune cells. This activates T-cells and boosts their ability to identify and fight tumor cells.
KEYNOTE-181 was designed to determine if Keytruda could outperform standard chemotherapy in patients with advanced or metastatic adenocarcinoma or squamous cell carcinoma (SCC) of the esophagus, or adenocarcinoma of the esophagogastric junction (EGJ) who had failed first-line standard treatment.
The trial included 628 patients who randomly received Keytruda — given as an infusion once every three weeks — or a chemotherapy chosen by the physician: Taxol (paclitaxel), Taxotere (docetaxel), or irinotecan.
Randomization was classified according to the type of tumor — SCC versus adenocarcinoma — and place of recruitment (Asia or elsewhere).
KEYNOTE-181’s primary goals were to determine if Keytruda extended survival among the overall population and in two patient subgroups — those with SCC (422 patients) and those whose tumors had 10% or more cells producing the PD-L1 factor (CPS greater than 10; 222 patients).
Secondary goals included the proportion of patients responding to treatment, time patients lived without signs of disease progression, and safety.
Keytruda was no better than chemotherapy in the overall population, with patients in both groups living for a median of 7.1 months. And while a clinically meaningful improvement was seen in SCC patients receiving Keytruda, the results did not meet the prespecified statistical significance.
However, patients with a CPS score of 10 or more saw their risk of death reduced by 31% — living a median of 9.3 months, compared to 6.7 months in the chemotherapy group. At 12 months, the estimated overall survival for these patients was 43% with Keytruda and 20% with chemotherapy.
Patients treated with Keytruda experienced fewer treatment-related adverse side effects (64.3% versus 86.1%) and serious adverse side effects (18.2% versus 40.9%) than those on chemotherapy. The most common side effects related to Keytruda were fatigue, low levels of thyroid hormones, decreased appetite, tiredness, nausea, and diarrhea.
“The significant improvement in overall survival observed with Keytruda in patients with squamous cell carcinoma or adenocarcinoma whose tumors expressed PD-L1 with a CPS of 10 or greater represents an important scientific advancement and has the potential to benefit patients who currently have limited treatment options,” said Kojima.
“Esophageal cancer often progresses aggressively, so we are encouraged to see these overall survival results for Keytruda as monotherapy in previously treated patients,” said Roy Baynes, senior vice president and head of global clinical development, and chief medical officer Merck Research Laboratories.
“Merck is committed to understanding the clinical benefit of Keytruda across a range of gastrointestinal cancers, including esophageal cancer. Along with other new data for Keytruda and from our broad oncology portfolio, we are pleased to share our latest clinical research in gastrointestinal cancers at ASCO GI,” Baynes added.