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Pembrolizumab in Microsatellite Instability–High Advanced Gastric or Gastroesophageal Junction Cancer


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In an analysis reported in JAMA Oncology, Joseph Chao, MD, and colleagues found improved outcomes with pembrolizumab treatment in patients with microsatellite instability–high (MSI-H) advanced gastric or gastroesophageal junction cancer, irrespective of line of treatment. The findings suggest that MSI-H status may be a biomarker for pembrolizumab benefit in these malignancies.

Joseph Chao, MD

Joseph Chao, MD

Study Details

The study involved identification of MSI-H status and assessment of prognosis among patients with advanced gastric or gastroesophageal junction cancer cancer receiving pembrolizumab as:

  • Third-line treatment or higher in the phase II single-arm KEYNOTE-059 trial
  • Second-line treatment in the phase III KEYNOTE-061 trial (vs paclitaxel)
  • First line-treatment with or without chemotherapy (cisplatin and fluorouracil or capecitabine vs chemotherapy alone).

MSI-H status was determined centrally by polymerase chain reaction testing.

Key Findings

At data cutoff, median follow-up durations were 5.6 months (range = 0.5­­­–37.6 months) in KEYNOTE-059, 7.9 months (range = 0.2–27.7 months) in KEYNOTE-061, and 11.3 months (range = 0.2–41.2 months) in KEYNOTE-062.

In KEYNOTE-059 (third-line treatment or higher), 7 (4.0%) of 174 patients had MSI-H tumors. Among these patients, median overall survival was not reached (95% confidence interval [CI] = 1.1 months–not reached), median progression-free survival was not reached (95% CI = 1.1 months–not reached), and objective response rate was 57.1%.

In KEYNOTE-061 (second-line treatment), 27 (5.3%) of 514 patients had MSI-H tumors, including 15 patients in the pembrolizumab group and 12 in the chemotherapy group. Median overall survival was not reached with pembrolizumab (95% CI = 5.6 months–not reached) vs 8.1 months (95% CI = 2.0–16.7 months) with chemotherapy alone. Median progression-free survival was 17.8 months (95% CI = 2.7 months–not reached) vs 3.5 months (95% CI = 2.0–9.8 months). Objective response rates were 46.7% vs 16.7%.

In KEYNOTE-062 (first-line treatment), 50 (7.3%) of 682 patients had MSI-H tumors, including 14 in the pembrolizumab group, 17 in the pembrolizumab/chemotherapy group, and 19 in the chemotherapy group. Median overall survival was not reached with pembrolizumab monotherapy (95% CI = 10.7 months–not reached) or with pembrolizumab/chemotherapy (95% CI = 3.6 months–not reached) compared with 8.5 months (95% CI = 5.3–20.8 months) with chemotherapy alone. Median progression-free survival was 11.2 months (95% CI = 1.5 months–not reached) for pembrolizumab and not reached (95% CI = 3.6 months–not reached) for pembrolizumab/chemotherapy, compared with 6.6 months (95% CI = 4.4–8.3 months) for chemotherapy alone. Objective response rates were 57.1% for pembrolizumab, 64.7% for pembrolizumab/chemotherapy, and 36.8% for chemotherapy alone.

Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced gastric or gastroesophageal junction cancer, regardless of the line of therapy in which it was received.
— Joseph Chao, MD, and colleagues

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The investigators concluded, “Findings from this study indicate that MSI-H status may be a biomarker for pembrolizumab therapy among patients with advanced gastric or gastroesophageal junction cancer, regardless of the line of therapy in which it was received.”

Dr. Chao, of the Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, is the corresponding author for the JAMA Oncology article.

Disclosure: The study was funded by Merck Sharp & Dohme, a subsidiary of Merck, and supported by a grant from the National Institutes of Health. For full disclosures of the study authors, visit jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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