FDA Approves Pembrolizumab for Esophageal Cancer Subgroup

The FDA approved the use of single-agent pembrolizumab (Keytruda) for the treatment of recurrent, locally advanced or metastatic squamous cell carcinoma of the esophagus. Tumors must express PD-L1 (CPS 10 or higher) and have progressed after 1 or more lines of therapy, according to Merck, the manufacturer of the immunotherapy agent.

As new agents are approved in this space, the role of the oncology nurse will become increasingly important, according to Sarbajit Mukerjee, MD, MD, an assistant professor in the department of Medicine - GI Medical Oncology at Roswell Park Comprehensive Cancer Center.

"Nurses always play a key role in the care of patients with squamous esophageal cancers, mostly related to teaching patients about their disease and symptom management related to the cancer and the treatments. With regards to pembrolizumab, there are some needed tests to establish whether these patients will be candidates for this therapy and there are some symptom and lab monitoring management issues associated with pembrolizumb therapy. For example we need to educate patients about and monitor their thyroid function as this can be impacted by pembrolizumab treatment," he said.

The approval was based off the KEYNOTE-181 trial, a multicenter, randomized, open-label, active-controlled trial that showed that patients given pembrolizumab experienced improved overall survival (OS) compared to those on the chemotherapy arm.

“Historically, patients with advanced esophageal cancer have had limited treatment options, particularly after their disease has progressed,” said Jonathan Cheng, MD, vice president, oncology clinical research, Merck Research Laboratories, in a release.

The trial included 628 patients with recurrent or locally advanced or metastatic esophageal cancer who progressed on at least 1 other line of systemic therapy. Participants whose disease was HER2/neutral positive received treatment with an approved HER2/neu targeted therapy.

All patients on the trial had to have tumor specimens for PD-L1 testing, which was determined using the PD-L1 IHC 22C3 pharmDx kit. Patients were randomized by tumor histology — esophageal squamous cell carcinoma or esophageal adenocarcinoma/Siewert type I EAC of the gastroesophageal function – and geographic region.

In KEYNOTE-181, patients were randomized to receive either 200 mg of pembrolizumab every 3 weeks or investigators’ choice of any of the following intravenous chemotherapy regimens:

• 80-100 mg/m2 of paclitaxel on days 1, 8, and 15 of every 4-week cycle
• 75 mg/m2 of docetaxel every 3 weeks
• 180 mg/m2 of irinotecan every 2 weeks

Median OS on the pembrolizumab arm was 10.3 months compared to 6.7 months on the chemotherapy arm. Average progression-free survival (PFS) was 3.2 months (range, 2.1-4.4 months) for pembrolizumab and 2.3 months (range, 2.1-3.4) on the chemotherapy arm.

Pembrolizumab had an overall response rate (ORR) of 22%, a complete response rate (CRR) of 5%, and a partial response rate (PR) of 18%. All 3 of these numbers bested the chemotherapy arm, which had an ORR of 7%, CRR of 1%, and PR of 6%. Median duration of response was 9.3 months and 7.7 months for patients receiving pembrolizumab and chemotherapy, respectively.

Those given pembrolizumab who did not have disease progression could be treated for up to 2 years. Pembrolizumab treatment continued until disease progression or unacceptable toxicity. Severe or potentially fatal immune-related adverse events include: pneumonitis, colitis, hepatitis, endocrinopathies, nephritis/renal dysfunction, skin reactions, solid organ transplant rejection, and complications with allogenic hematopoietic stem cell transplant. Practitioners should analyze the severity of reactions and decide if discontinuation of treatment or the administration of corticosteroids is most appropriate.

Findings from the KEYNOTE-180 trial also contributed to the FDA’s approval. This multicenter, non-randomized, open-label trial included 121 patients with locally advanced or metastatic esophageal cancer who progressed on 2 or more systemic therapies for their advanced disease. All other enrollment criteria were identical to KEYNOTE-181.

ORR in KEYNOTE-180 was 20% for patients with esophageal squamous cell carcinoma who had PD-L1 expression (CPS 10 or higher). Seven patients total responded to treatment. Among them, duration of response ranged from 4.2 to 25.1 months or more. Seventy-one percent (5 patients) had responses that lasted 6 months or longer, and 57% (3 patients) had responses that lasted 12 months or longer.

“With this approval, Keytruda is now the first anti-PD-1 therapy approved for the treatment of previously-treated patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10), providing an important new monotherapy option for physicians and patients in the United States,” Cheng said.