Keytruda (pembrolizumab) is safe and has shown promising anti-tumor activity in patients with advanced gastric or gastroesophageal junction (GEJ) cancer, according to data presented at the European Society for Medical Oncology (ESMO) 2017 Congress.
The drug alone was effective in treating patients who had failed at least two prior chemotherapy regimens and in newly-diagnosed patients. And 60 percent of patients treated with a combination of Keytruda and chemotherapy saw their tumors shrink.
The study, “KEYNOTE-059 Update: Efficacy and Safety of Pembrolizumab Alone or in Combination With Chemotherapy in Patients With Advanced Gastric or Gastroesophageal (G/GEJ) cancer,” was presented by Zev A. Wainberg, from Medicine Hematology and Oncology at UCLA’s David Geffen School of Medicine in Los Angeles. It was based on updated data from the Phase 2 KEYNOTE-059 study (NCT02335411).
The KEYNOTE-059 study was designed to test Keytruda as a stand-alone agent and in combination with chemotherapy as a treatment for recurrent or metastatic gastric/GEJ adenocarcinoma.
Participants were included in one of three cohorts (groups). Cohort 1 is testing Keytruda alone in 259 patients whose disease progressed despite two prior chemotherapy regimens. Cohort 2 recruited 25 newly diagnosed patients and administered a combination of Keytruda and the chemotherapy Platinol (cisplatin) plus 5-fluorouracil, or Xeloda (capecitabine).
In Cohort 3, 31 newly diagnosed patients with PD-L1-positive tumors were given Keytruda alone. A positive PD-L1 tumor was determined as a positive score of 1 percent or more in the PD-L1 IHC 22C3 pharmDx assay.
Keytruda was administered in a 200 mg dose every three weeks for up to two years in all cohorts. The study primarily aimed to assess safety in all three cohorts and to determine the objective response rate (ORR) in cohorts 1 and 3. Secondary measures included ORR, duration of response, progression-free survival, and overall survival in cohort 2.
During the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, researchers presented data from Cohorts 1 and 2 showing that Keytruda had a manageable safety profile and promising antitumor activity.
Now, after a median follow-up of six, 14, and 18 months for cohorts 1, 2, and 3, respectively, researchers provided new efficacy data.
In cohort 1, 12 percent of patients achieved either a partial or a complete response to Keytruda. More patients with PD-L1-positive tumors responded — 16 percent versus 6 percent of PD-L1-negative tumors. Patients were alive without disease progression for a median of two months and survived for a median of six months.
Among those who received Keytruda plus chemotherapy as their first therapy (cohort 2), 60 percent responded. As in cohort 1, ORR was higher in patients with PD-L1-positive tumors — 73 percent vs. 38 percent. Patients who responded took a median of seven months before seeing their cancer progress and lived for a median of 14 months.
First-line therapy with Keytruda induced tumor shrinkage in 26 percent of patients in cohort 3. The disease progressed within a median of three months, but after 18 months of follow-up, more than half of patients were still alive.
The incidence of treatment-related adverse events (TRAEs) was 18 percent, 76 percent, and 23 percent of patients for cohorts 1, 2, and 3, respectively. Three percent and 12 percent of patients in cohort 1 and 2 discontinued treatment due to severe TRAEs.
Overall, the team believes their findings support Keytruda’s manageable safety and therapeutic efficacy in patients with advanced gastric/GEJ cancer.
Based on KEYNOTE-059 data, a supplemental biologics license application was submitted to the U.S. Food and Drug Administration (FDA) proposing Keytruda as a treatment for patients following at least two lines of therapy for recurrent or advanced gastric or GEJ adenocarcinoma. The application is under review and a decision is expected by Sept. 22, 2017.