Pembrolizumab shows modest activity in advanced esophageal cancer

Last Updated: 2018-12-27

By David Douglas

NEW YORK (Reuters Health) - Pembrolizumab benefits a minority of heavily pretreated patients with advanced metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, according to an open-label phase 2 trial.

"Similar to gastric cancer, we see that anti PD-1 antibody therapy has modest activity in esophageal adenocarcinoma," Dr. Manish A. Shah told Reuters Health by email. ". . . However, for patients who do respond, this is a meaningful and important option, and does fill an unmet medical need."

In a December 20 online paper in JAMA Oncology Dr. Shah, of Weill Cornell Medicine and New York-Presbyterian Hospital, New York City, and colleagues report on 121 patients who had undergone three or more therapies before receiving pembrolizumab, intravenously every three weeks for up to two years. The median number of treatment sessions was 4.0.

After a median overall follow-up of 5.8 months, 12 patients (9.9%) showed an objective response. This amounted to 14.3% of those with esophageal squamous cell carcinoma and 5.2% of those with adenocarcinoma. Response was higher in patients with PDL1-positive tumors (13.8% versus 6.3%). In addition, at a median follow-up of 13.3 months among responders, the median duration of response was not reached.

Survival outcomes were altogether encouraging, say the investigators, with a median overall survival of 5.8 months, a 6-month OS rate of 49% and a 12-month OS rate of 28%. This they point out compares favorably "with the historically observed median OS of less than 4 months and a 12-month OS rate of less than 13% in the second-line setting."

Only five patients discontinued treatment because of adverse events. The researchers observe that "where effective treatment options are an unmet need, pembrolizumab provided durable antitumor activity with manageable safety."

Randomized studies testing pembrolizumab as first- and second-line therapy for metastatic esophageal cancer are underway, the research team notes.

Commenting by email, Dr. Benjamin A. Weinberg of Lombardi Comprehensive Cancer Center at Georgetown University, Washington DC, told Reuters Health the results "support at least trying pembrolizumab in refractory advanced esophageal cancer. The response rate is very low (9.9%), but this is still clinically significant in the third-line setting (usually you get less response with each subsequent line of therapy). In addition, 20.7% of patients had stable disease, with a disease control rate of 30.6%."

However, he noted, the median response time was long at 4.1 months "and the median duration of treatment was only 2.0 months, implying that patients either rapidly progress or need a while to get an objective response."

Moreover, added Dr. Weinberg, "Patients in the third line setting often cannot wait four months for a response because they're symptomatic from their cancer and need tumor shrinkage as soon as possible. In the third line without many other treatment options giving pembrolizumab makes sense, but immunotherapy probably should be moved up to the second or even first line." By doing so, "there is a longer time horizon for patients who will take a while to respond to immunotherapy to get that chance."

SOURCE: http://bit.ly/2GLlFKX

JAMA Oncol 2018.