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.


Can Statin Use After Diagnosis of Esophageal Cancer Prolong Survival? (AGA Journals)

March 29, 2016


“Statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, reduces esophageal cancer–specific and all-cause mortality, researchers report in the April issue of Gastroenterology.

Esophageal cancer is the fifth most common cause of cancer-related death in men and eighth most common cause in women, worldwide. Esophageal squamous cell carcinomas (ESCC) are the most common histologic subtype worldwide, but the incidence of esophageal adenocarcinoma (EAC) has increased rapidly since the 1970s and the most common form in the West. Fewer than 20% of patients with esophageal cancer survive for 5 years.

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are cholesterol-lowering drugs that have also been reported to have anti-cancer effects. Statin use after diagnosis has been associated with a reduced risk of cancer-specific mortality in from prostate, breast, and colorectal carcinomas. Statins were also found to reduce risk of liver cancer.

Statin use has been inversely associated with the development of the histologic subtypes of esophageal cancers. However, it is not clear whether statin use after a diagnosis of esophageal cancer prolongs survival, or has different effects on EAC vs ESCC.

Leo Alexandre et al sought to determine whether statin use after a diagnosis of esophageal cancer reduced cancer-specific and all-cause mortality in a large cohort (4445 men and women) in the United Kingdom. They collected their data from the United Kingdom General Practice Research database, the UK National Cancer Registry, and the Office of National Statistics database.”

To read more about the findings, visit:


Microendoscope may eliminate biopsies for patients undergoing screening for esophageal cancer, study.

June 4, 2015

Rice University device nearly doubled sensitivity of esophageal cancer screenings

In a clinical study of patients in the United States and China, researchers found that a low-cost, portable, battery-powered microendoscope developed by Rice University bioengineers could eventually eliminate the need for costly biopsies for many patients undergoing standard endoscopic screening for esophageal cancer.

The research is available online in the journal Gastroenterology and was co-authored by researchers from nearly a dozen institutions that include Rice, Baylor College of Medicine, the Chinese Academy of Medical Sciences and the National Cancer Institute.

The clinical study, which involved 147 U.S. and Chinese patients undergoing examination for potentially malignant squamous cell tumors, explored whether Rice’s low-cost, high-resolution fiber-optic imaging system could reduce the need for unnecessary biopsies when used in combination with a conventional endoscope — the worldwide standard of care for esophageal cancer diagnoses.

The study involved patients from two U.S. and two Chinese hospitals: Mt. Sinai Medical Center in New York, the University of Texas MD Anderson Cancer Center in Houston, the Cancer Institute and Hospital of the Chinese Academy of Medical Sciences in Beijing and First University Hospital in Jilin, China.

In the study, all 147 patients with suspect lesions were examined with both a traditional endoscope and Rice’s microendoscope. Biopsies were obtained based upon the results of the traditional endoscopic exam.

A pathology exam revealed that more than half of those receiving biopsies — 58 percent — did not have high-grade precancer or cancer. The researchers found that the microendoscopic exam could have spared unnecessary biopsies for about 90 percent of the patients with benign lesions.

In these images from Rice’s high-resolution microendoscope, the white spots are cell nuclei, which are irregularly shaped and enlarged in cancerous tumors (right) as compared with healthy tissue (left). Credit: Richards-Kortum Lab/Rice University


“For patients, biopsies are stressful and sometimes painful,” said lead researcher Rebecca Richards-Kortum, Rice’s Stanley C. Moore Professor of Bioengineering, professor of electrical and computer engineering and director of Rice 360°: Institute for Global Health Technologies. “In addition, in low-resource settings, pathology costs frequently exceed endoscopy costs. So the microendoscope could both improve patient outcomes and provide a significant cost-saving advantage if used in conjunction with a traditional endoscope.”

When examined under a microscope, cancerous and precancerous cells typically appear different from healthy cells. The study of cellular structures is known as histology, and a histological analysis is typically required for an accurate diagnosis of both the type and stage of a cancerous tumor.

To determine whether a biopsy is needed for a histological exam, health professionals often use endoscopes, small cameras mounted on flexible tubes that can be inserted into the body to visually examine an organ or tissue without surgery. Rice’s high-resolution microendoscope uses a 1-millimeter-wide fiber-optic cable that is attached to the standard endoscope. The cable transmits images to a high-powered fluorescence microscope, and the endoscopist uses a tablet computer to view the microscope’s output. The microendoscope provides images with similar resolution to traditional histology and allows endoscopists to see individual cells and cell nuclei in lesions suspected of being cancerous.

By providing real-time histological data to endoscopists, Rice’s microendoscope can help rule out malignancy in cases that would otherwise require a biopsy.

“While traditional endoscopy can rule out malignancy and eliminate the need for biopsies for some patients, in a significant number of cases the difference between malignant and benign lesions only becomes apparent through a histological analysis,” said study co-author Dr. Sharmila Anandasabapathy, professor of medicine and gastroenterology at Baylor College of Medicine and director of Baylor Global Initiatives and the Baylor Global Innovation Center.

Richards-Kortum’s lab specializes in the development of low-cost optical imaging and spectroscopy tools to detect cancer and infectious disease at the point of care. Her research group is particularly interested in developing technology for low-resource settings, and the microendoscope was developed as part of that effort. It is battery-operated, inexpensive to operate and requires very little training. Results from the clinical study verified that both experienced and novice endoscopists could use the microendoscope to make accurate assessments of the need for a biopsy.

Clinical studies of Rice’s microendoscope are either planned or underway for a dozen types of cancer including cervical, bladder, oral and colon cancers.

“More than half of cancer deaths today occur in the developing world, often in low-resource areas,” Anandasabapathy said. “The World Health Organization and other important international bodies have called for increased global focus on noncommunicable diseases like cancer, and Rice’s microendoscope is a great example of what the right kind of technology can do to change health care in low-resource countries.”

The research was supported by the National Cancer Institute. This post is based on materials provided by a Rice University press release, which can be accessed here:


Proton therapy has fewer side effects in esophageal cancer patients, study finds.

May 26, 2015

New research by scientists at the University of Maryland School of Medicine has found that esophageal cancer patients treated with proton therapy experienced significantly less toxic side effects than patients treated with older radiation therapies.

Working with colleagues at the Mayo Clinic in Rochester, Minnesota and the MD Anderson Cancer Center in Dallas, Texas, Michael Chuong, MD, an assistant professor of radiation oncology at the school, compared two kinds of X-ray radiation with proton therapy, an innovative, precise approach that targets tumors while minimizing harm to surrounding tissues.

The researchers looked at nearly 600 patients and found that proton therapy resulted in a significantly lower number of side effects, including nausea, blood abnormalities and loss of appetite. The results were presented on May 22 at the annual conference of the Particle Therapy Cooperative Group, held in San Diego.

“This evidence underscores the precision of proton therapy, and how it can really make a difference in cancer patients’ lives,” said Dr. Chuong.

Patients with esophageal cancer can suffer a range of side effects, including nausea, fatigue, lack of appetite, blood abnormalities and lung and heart problems. Proton therapy did not make a difference in all of these side effects, but had significant effects on several.

The results have particular relevance for the University of Maryland School of Medicine; this fall the school will open the Maryland Proton Treatment Center (MPTC). The center will provide one of the newest and highly precise forms of radiation therapy available, pencil beam scanning (PBS), which targets tumors while significantly decreasing radiation doses to healthy tissue. This technique can precisely direct radiation to the most difficult-to-reach tumors.

esophageal cancer patients proton therapy new research study findings esophagus cancer patients

The National Association for Proton Therapy


Proton therapy is just one of several new methods for treating cancer. Others include:

  • Selective Internal Radiation Therapy, a precision modality for treating patients with particularly difficult-to-remove tumors involving the liver such as those from colorectal cancers;
  • Gammapod, a new, high-precision, noninvasive method of treating early-stage breast cancer;
  • Thermal Therapies, the use of “heat” in treating a broad spectrum of malignancies.

The treatment works well for many kinds of tumors, including those found in the brain, esophagus, lung, head and neck, prostate, liver, spinal cord and gastrointestinal system. It is also an important option for children with cancer and is expected to become an important option for some types of breast cancer. While most cancer patients are well served with today’s state-of-the-art radiation therapy technology, up to 30 percent are expected to have a greater benefit from the new form of targeted proton beam therapy.

This post is based on information provided by University of Maryland.


“Clinical Trials Actively Recruiting Patients With Esophageal Cancer,” The ASCO Post

March 26, 2015

By Liz Janetschek | The ASCO Post.  March 25, 2015, Volume 6, Issue 5

The information contained in this Clinical Trials Resource Guide includes actively recruiting observational, interventional, phase I, phase II, and phase III clinical studies for patients with newly diagnosed or recurrent esophageal cancer. All of the studies are listed on the National Institutes of Health website at

Read the full article, “Clinical Trials Actively Recruiting Patients With Esophageal Cancer,” The ASCO Post.