FDA Approves Keytruda to Treat Esophageal Cancer, Squamous Cell Carcinoma

July 31, 2019

The FDA approved pembrolizumab as monotherapy for certain patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus.

The approval applies to use of pembrolizumab (Keytruda, Merck) for patients whose tumors express PD-L1 — with a combined positive score of 10 or higher — as determined by an FDA-approved test, and who experienced disease progression after one or more previous lines of systemic therapy.

“Historically, patients with advanced esophageal cancer have had limited treatment options, particularly after their disease has progressed,” Jonathan Cheng, MD vice president for oncology clinical research at Merck Research Laboratories, said in a press release. “With this approval, Keytruda is now the first anti-PD-1 therapy approved for the treatment [for this patient population], providing an important new monotherapy option for physicians and patients in the United States.”

Squamous cell carcinoma is cancer that begins in squamous cells of the esophagus. Squamous cells are thin, flat cells that look like fish scales, and are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the lining of the respiratory and digestive tracts.  Esophageal squamous cell carcinoma is most often found in the upper and middle part of the esophagus, but can occur anywhere along the esophagus.

Esophageal squamous cell carcinoma

The FDA based the approval on results from the randomized controlled KEYNOTE-181 trial, which included 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced disease.

Researchers randomly assigned patients 1:1 to pembrolizumab 200 mg every 3 weeks or investigator’s choice of IV chemotherapy with paclitaxel, docetaxel or irinotecan. Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

OS among three groups — patients with esophageal squamous cell carcinoma, those whose tumors express PD-L1 with a combined positive score of 10 or higher, and all randomly assigned patients — served as the key efficacy outcome.

Secondary outcomes included PFS, objective response rate and duration of response.

Researchers reported HRs for OS of 0.77 (95% CI, 0.63-0.96) among patients with esophageal squamous cell carcinoma; 0.7 (95% CI, 0.52-0.94) among patients whose tumors met the defined PD-L1 expression threshold; and 0.89 (95% CI, 0.75-1.05) among all randomly assigned patients.

Among patients with esophageal squamous cell carcinoma who met the defined PD-L1 expression threshold, those assigned pembrolizumab achieved longer median OS (10.3 months vs. 6.7 months; HR = 0.64; 95% CI, 0.46-0.9) and median PFS (3.2 months vs. 2.3 months; HR = 0.66; 95% CI, 0.48-0.92).

A higher percentage of pembrolizumab-treated patients achieved response (22% vs. 7%), complete response (5% vs. 1%) and partial response (18% vs. 6%). Median duration of response was 9.3 months in the pembrolizumab group and 7.7 months in the chemotherapy group.

Adverse reactions that occurred among pembrolizumab-treated patients with esophageal cancer appeared similar to those that have been observed among patients with melanoma or non-small cell lung cancer who received pembrolizumab monotherapy.

The FDA also considered data from the KEYNOTE-180 trial, a nonrandomized, open-label study that included 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease.

Thirty-five patients with esophageal squamous cell carcinoma expressed PD-L1 with a combined positive score of 10 or higher. Seven patients achieved response, equating to an ORR of 20%. The duration of response ranged from 4.2 months to more than 25.1 months. Five patients achieved responses that lasted 6 months or longer, and three patients achieved responses that lasted 12 months or longer.

In patients with esophageal cancer, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Editor Note: Content may be edited.


Imagine A World With No Tobacco

May 31, 2014

World No Tobacco Day is Saturday, May 31, 2014.  Tobacco use has been linked to a number of health related problems. The use of tobacco products has been linked to lethal diagnoses such as heart disease, stroke, cancer, Chronic Obstructive Pulmonary Disease (COPD) and emphysema. Tobacco use is also linked to non-life-threatening issues such as yellow teeth, bad breath, pre-mature aging of the skin, vision loss and not to mention a significant financial burden.

Tobacco products include but are not limited to: cigarettes, cigarette tobacco, chewing tobacco, roll-your-own tobacco, and smokeless tobacco. Use of all of these aforementioned products increases the risk of developing esophageal cancer.

The American Cancer Society reports that smokers who smoke a pack a day have double the risk of developing esophageal cancer than a nonsmoker. The risk further increases when combined with other risk factors such as chronic heartburn, Gastroesophageal Reflux Disease (GERD), family history of cancer, obesity, Barrett’s Esophagus, poor nutrition, and excessive alcohol use.

But! There is good news. The risk of esophageal cancer has the potential of decreasing the sooner one stops using tobacco and the longer that they stay away from tobacco products. The body begins to immediately repair itself. In fact, within just 8 hours, carbon monoxide levels in the blood drops to normal and oxygen levels increase to normal.*

“In March 2012, the Centers for Disease Control and Prevention (CDC) launched the first-ever paid national tobacco education campaign—Tips From Former Smokers (Tips). Tips encourages people to quit smoking by showing the toll that smoking-related illnesses take on smokers and their loved ones. The hard-hitting ads show people living with the real and painful consequences of smoking or exposure to secondhand smoke.”

If you or someone you know is ready to quit, visit CDC’s website and utilize their “Tips Guide” to quit now and quit for good.

Join us in spreading the word about the dangers of tobacco use by using the social media links below!