FDA’s Approval of Keytruda-Based Regimen for Certain Stomach Cancer Subtypes ‘Really Exciting’ For Patients

The Food and Drug Administration’s (FDA) recent approval of Keytruda (pembrolizumab) for use with trastuzumab, fluoropyrimidine-and platinum-containing chemotherapy for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma is a great development for patients, according to an expert from Memorial Sloan Kettering Cancer Center.

“It's really exciting,” Dr. Yelena Janjigian, a medical oncologist and chief of gastrointestinal oncology service at Memorial Sloan Kettering Cancer Center in New York, said in an interview with CURE®. “HER2-positive disease has been under study and scrutiny for so many years, and the last approval was over a decade ago. So for the first time, we were able to change practice, and indicate that the combination of HER2-directed therapy plus anti-PD1 therapy … (has) an additive effect and higher overall response rate.”

These diseases, according to Janjigian, are relatively common across the world. And depending on the location and patient subset being observed, she noted that approximately 20% of esophageal and gastric adenocarcinomas are HER2-positive. However, Janjigian highlighted that gastric cancers are less common in the United States. In fact, gastric cancer is considered a rare disease in the U.S. as there are approximately 20,000 to 30,000 cases each year. But that doesn’t mean little attention should be given to the disease.

“The type of gastroesophageal and G junction tumors that are more prevalent in the U.S. ... and those cancers are actually on the rise in the U.S. and the Western world, particularly among younger patients,” she said.

What The Results Showed

The FDA’s accelerated approval was based on an analysis of 264 patients with HER2-positive advanced gastric or GEJ adenocarcinoma from the ongoing KEYNOTE-811 trial. Data demonstrated that the overall response rate (or the percentage of patients with partial or complete response to a therapy) was 74% in patients assigned Keytruda compared with 52% in those assigned to the placebo group. Moreover, patients in the Keytruda group had a longer median duration of response compared with those in the placebo group (10.6 months versus 9.5 months).

Janjigian explained how these results and subsequent approval were significant.

“To show a dramatic improvement in overall response rate in (this) space is relatively unusual,” she said. “Typically, these drugs get approved based on incremental benefit for survival measured in months.”

The survival data for this population are not yet available, but as Janjigian mentioned, the approval was based on a robust overall response effect that typically is not seen in a phase 3 setting.

“When you have such deep responses that are meaningful, some of these patients live with their disease for years,” she said. “That's really where the innovation comes and why it is an exciting … exciting change (for patients) because we have not seen this. This (is) not something that we've been able to overcome in gastric cancer. With HER2-positive breast cancer, people live for years even with stage four disease. But unfortunately, typically in gastric cancer, a lot of the drugs that succeeded in breast failed in gastric, so the landscape for HER2 disease was relatively empty.”

Significance of a Firstline Approval

Typically, according to Janjigian, most patients in the U.S. as well as across Europe are diagnosed with stage 4 disease. Unfortunately, she said, surgery is not often an option for those patients. She explained how patients are told that although their disease is not curable, it is still treatable.

“It's important to try to get the disease under control quickly,” she said. “Because if the patient's clinical status deteriorates, and they're not able to eat or they're in so much pain that they can't make it out of bed, the likelihood they're going to be able to turn that around with subsequent treatments is very low.”

That’s why Janjigian said she designed the trial, which led to the approval, to administer the regimen as soon as patients were diagnosed.

“If you wait and try to do it in second-line or third-line setting, the problem is (that) over time, the patients become clinically more frail (and) are less likely to be able to get treatment,” she explained.

In fact, data indicate that less than 40% of patients in some countries make it to receive second-line treatment, according to Janjigian.

“The initial results in this clinical setting (have) not been seen before,” she concluded. “So (this is) very promising.”

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