Pembrolizumab Gastric Cancer Data Updated, as FDA Considers Approval

Charles S. Fuchs, MD, MPH

Pembrolizumab continued to show promising signs of clinical activity as a treatment for patients with advanced gastric or gastroesophageal junction (GEJ) cancer in updated findings from the KEYNOTE-059 study presented at the 2017 ASCO Annual Meeting.

The objective response rate (ORR) with pembrolizumab was 11.6%. In those who specifically received 2 prior lines of therapy, the ORR was 16.4%. The median progression-free survival (PFS) was 2.0 months and the median overall survival (OS) was 5.6 months, with a 12-month OS rate of 23.4%.

The latest update included findings from patients with microsatellite instability-high (MSI-H) tumors, which was 4% of enrolled patients (n = 7). In this group, the ORR with pembrolizumab was 57.1% and the CR rate was 14.3%. The disease control rate (DCR) was 71.4%. In those with non-MSI-H tumors (n = 167), the ORR was 9% and the CR rate was 2.4%. The disease control rate was 22.2%.

A supplemental biologics license application based on data from the KEYNOTE-059 study was accepted by the FDA for a priority review in May 2017 for pembrolizumab as a treatment for patients following at least 2 courses of therapy for recurrent or advanced gastric or GEJ adenocarcinoma. The agency is expected to announce a decision by September 22, 2017.

"Pembrolizumab represents a potential treatment option for patients with gastric/GEJ cancer who have progression after at least 2 prior lines of therapy," said lead investigator Charles S. Fuchs, MD, MPH, director of Yale Cancer Center and Physician-in-Chief of Smilow Cancer Hospital. "Ongoing randomized clinical trials are now assessing pembrolizumab in earlier lines of therapy and in combination with chemotherapy regimens for patients with advanced gastric and GEJ cancer."

In the KEYNOTE-059 trial, 259 patients received pembrolizumab at a flat 200 mg dose every 3 weeks. The median age of patients was 62 years and 76.4% were male. The ECOG performance status for patients was primarily 0 (41.3%) and 1 (58.3%). Overall, 51.7% of patients had received 2 prior lines of therapy, and 29% and 19.3% had received 3 or ≥4 prior lines of therapy, respectively.

After a median follow-up of 5.8 months, 2.3% of patients had a complete response (CR) and 9.3% had a partial response. When including stable disease, the disease control rate was 27%. The median duration of response (DOR) was 8.4 months.

Patients with PD-L1—positive tumors (n = 148) had an ORR of 15.5%, with 2% having a CR. The ORR was 6.4% in the PD-L1–negative group (n = 109), with a 2.8% CR rate. The median DOR in the PD-L1–positive group was 16.3 versus 6.9 months in those with PD-L1–negative disease.

Those treated in the third-line setting had a 3% CR rate and a 13.4% partial response rate. In the fourth-line and beyond, the ORR dropped to 6.4%, with a 1.6% CR rate. For those with PD-L1—positive tumors in the third-line setting (n = 75), the ORR was 22.7% with a 2.7% CR rate. In patients with PD-L1–negative tumors treated with third-line pembrolizumab (n = 58), the ORR was 8.6% with a 3.4% CR rate.

"Pembrolizumab demonstrated promising antitumor activity and durable responses in patients with advanced gastric/GEJ cancer progression after more than 2 lines of therapy," said Fuchs. "ORR was higher in patients with PD-L1—positive tumors but responses were also observed in patients with PD-L1–negative tumors."

The most frequently occurring treatment-related adverse events (AEs) of all grades were fatigue (18.9%), pruritus (8.9%), rash (8.5%), hypothyroidism (7.7%), decreased appetite (7.3%), anemia (6.9%), nausea (6.9%), diarrhea (6.6%), and arthralgia (5.8%). There were 2 treatment-related grade 5 AEs (acute kidney injury and pleural effusion).

Pembrolizumab is approved for several indications, including as a treatment for patients with lung cancer, melanoma, Hodgkin lymphoma, and other types of cancer. In mid-May, the FDA granted an accelerated approval to pembrolizumab as a treatment for patients without other options with unresectable or metastatic, MSI-H or mismatch repair deficient (dMMR) solid tumors. This was in addition to those with MSI-H or dMMR colorectal cancer following progression on a fluoropyrimidine, oxaliplatin, and irinotecan.

Fuchs CS, Doi T, Jang RW-J, et al. KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. J Clin Oncol. 2017;35 (suppl; abstr 4003).

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