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CHICAGO -- First-line pembrolizumab (Keytruda) offered non-inferior overall survival (OS) versus standard chemotherapy in patients with advanced gastric cancer, a researcher reported here.

In the phase III KEYNOTE-062 trial, the median OS with pembrolizumab monotherapy was 10.6 months versus 11.1 months for chemotherapy (P=0.162 for superiority), according to Josep Tabernero, MD, PhD, of Vall d'Hebron Barcelona Hospital University Hospital and Institute of Oncology.

At 1 year, 47% of patients on pembrolizumab were alive compared with 46% of patients who received chemotherapy, a non-significant difference that fulfilled the pre-specified non-inferiority criteria, he said at a press conference at the American Society of Clinical Oncology (ASCO) annual meeting.

Tabernero also noted that at 24 months, 27% of the patients with PD-L1-positive, HER2-negative, advanced gastric or gastroesophageal junction cancer assigned to pembrolizumab monotherapy were alive versus 19% of patients who were treated with chemotherapy.

However, a combination of pembrolizumab and chemotherapy did not offer patients a benefit over chemotherapy alone. In patients with a PD-L1 combined positive score (CPS) of ≥10, 51% were alive at 1 year on the pembrolizumab-chemo combination versus 47% on chemotherapy alone. The median OS was 12.3 months versus 10.8 months (P=0.158), respectively. At 24 months, 28% of patients with a high CPS taking the combination therapy were alive versus 22% on chemotherapy.

KEYNOTE-062 had 763 patients (median age 62) with a PD-L1 CPS ≥1 who were randomized 1:1:1 to receive one of the following treatment protocols:

• 256 patients: 200 mg pembrolizumab every 3 weeks for up to 2 years
• 257 patients: The same regimen as above plus chemotherapy (80 mg/m² cisplatin plus 800 mg/m²/day fluorouracil on days 1 through 5 every 3 weeks or 1,000 mg/m² capecitabine twice daily on days 1 through 14 every 3 weeks per local guidelines)
• 250 patients: placebo every 3 weeks plus chemotherapy

Patients were in treatment until unacceptable toxicity, disease progression, or patient/physician withdrawal decision. Primary endpoints included OS in CPS ≥1 and CPS ≥10 patients for the study regimen versus chemotherapy, and for pembrolizumab versus chemotherapy. Secondary endpoints were overall response rate (ORR) per RECIST central review in CPS ≥1 patients for the combination therapy regimen versus chemotherapy, and safety.

The authors reported that the median OS was superior in the pembrolizumab arm at 17.4 months (95% CI 9.1-23.1) for those with CPS ≥10 versus standard chemotherapy at 10.8 months (95% CI 8.5-13.8, HR 0.69, 95% CI 0.49-0.97).

Also, the ORR was higher among those who received pembrolizumab in addition to chemotherapy, they stated.

Patients on pembrolizumab alone had the lowest rates of serious adverse events (AEs) at 16.9%, followed by chemotherapy alone (69.3%), and pembrolizumab plus chemotherapy (73.2%). The most common AEs included nausea and fatigue.

Overall, 22% of patients experienced immune-related toxicities, Tabernero said, but he pointed out that the safety profile of pembrolizumab was consistent with previous reports of the agent.

He noted that background therapy, age, sex, performance status, tumor location, histological subtypes of disease, number of metastatic sites, tumor size, and prior gastrectomy status had little influence on the outcomes.

ASCO press conference moderator Richard Schilsky, MD, ASCO chief medical officer, said, "This is a tough disease to treat. The patients are often older, they are frail and, until recently, the only available treatment had been platinum-based cytotoxic chemotherapy, which is difficult to tolerate. This has been a disease for which we have been desperate for new approaches. This study which demonstrates the promise of immunotherapy is important."

"It is certainly reasonable from the results of the study that pembrolizumab is not inferior to chemotherapy in treatment of gastric cancer patients," Schilsky said. "Does that mean it is better than chemotherapy? No. It does mean that it is not worse than chemotherapy. Along with the better side affect profile, it would appear to me that pembrolizumab is the preferred way to treat these patients."

He added that "What I take away from this study is for patients with advanced gastric/gastroesophageal cancer, pembrolizumab should really, in many cases, replace chemotherapy in the first-line treatment of this population."

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