Gastric Cancer: Pembrolizumab as Potential New First-Line Standard Therapy

KEYNOTE-062 Trial Results

• July 8, 2019
• Reading time: 2 minutes

Between May 31 and June 4, 2019, the ASCO 2019 Annual Meeting in Chicago presented results from the KEYNOTE-062 Phase III clinical trial evaluating the safety and efficacy of pembrolizumab monotherapy as first-line treatment for gastric and gastroesophageal junction cancer.

Trial Design and Treatment Arms

KEYNOTE-062 was a Phase III randomized controlled trial with three parallel treatment arms:

Arm 1 - Pembrolizumab Monotherapy:

• Pembrolizumab 200 mg IV on Day 1
• Every 3 weeks

Arm 2 - Pembrolizumab Plus Chemotherapy:

• Pembrolizumab 200 mg IV on Day 1
• Plus Cisplatin 80 mg/m² on Day 1
• Plus 5-Fluorouracil 800 mg/m²/day on Days 1-5, or Capecitabine 1,000 mg/m² twice daily on Days 1-14
• Every 3 weeks

Arm 3 - Placebo Plus Chemotherapy (Control):

• Placebo on Day 1
• Plus Cisplatin 80 mg/m² on Day 1
• Plus 5-Fluorouracil 800 mg/m²/day on Days 1-5, or Capecitabine 1,000 mg/m² twice daily on Days 1-14
• Every 3 weeks

Primary endpoints: progression-free survival and overall survival

Patient Demographics

• Median Age: 62 years
• Tumor Location: Gastric cancer 69%, gastroesophageal junction cancer 30%
• PD-L1 Expression: Combined Positive Score (CPS) ≥1 in 100% of patients; CPS ≥10 in 37% (N=281 patients)

Clinical Trial Results

CPS ≥1 Subgroup (All Enrolled Patients)

Overall Survival (Primary Endpoint):

• Pembrolizumab monotherapy: 10.6 months
• Chemotherapy: 11.1 months
• Hazard Ratio: 0.91

Pembrolizumab monotherapy demonstrated non-inferior overall survival compared to chemotherapy control, meeting trial criteria for equivalence.

CPS ≥10 Subgroup (PD-L1 High-Expressing Tumors)

Overall Survival:

• Pembrolizumab monotherapy: 17.4 months
• Chemotherapy: 10.8 months
• Hazard Ratio: 0.69

2-Year Overall Survival Rate:

• Pembrolizumab: 39%
• Chemotherapy: 22%

Safety Profile

Grade 3+ Adverse Event Incidence:

• Pembrolizumab monotherapy: 17%
• Pembrolizumab plus chemotherapy: 73%
• Chemotherapy alone: 69%

Pembrolizumab monotherapy demonstrated the lowest adverse event rate. Most common treatment-related events included nausea and fatigue. No novel, unexpected adverse events were identified; safety profile was consistent with prior immunotherapy trials.

Clinical Conclusions

Principal investigator Josep Tabernero concluded that in PD-L1 positive, HER2-negative gastric and gastroesophageal junction cancer patients, first-line pembrolizumab monotherapy demonstrates overall survival outcomes comparable to or superior to chemotherapy, potentially establishing a new first-line standard treatment approach.

Related Gastric Cancer Treatment

• Immunotherapy
• Clinical Trial Therapeutics
  • (Lung Cancer) Topotecan and Topotecan Plus Berzosertib Phase II Trial Results
  • (Lung Cancer) HER2-Mutant Non-Small Cell Lung Cancer Treatment with Enhertu
  • (Lung Cancer) Anti-B7-H3 Antibody DS-7300 Clinical Efficacy

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