Pembrolizumab Active in PD-L1–Positive Advanced Gastric and Metastatic Triple-Negative Breast Cancers

Key Points

  • Pembrolizumab showed activity in both PD-L1–positive advanced gastric cancer and metastatic triple-negative breast cancer.
  • Further study of pembrolizumab in both patient populations is warranted.

As reported by Muro et al in The Lancet Oncology and Nanda et al in the Journal of Clinical Oncology, single-agent pembrolizumab (Keytruda) showed activity in programmed cell death ligand 1 (PD-L1)–positive advanced gastric cancer and metastatic triple-negative breast cancer in the KEYNOTE-012 phase Ib trial.

Study Details

The trial was performed at 13 sites in the United States, Israel, Japan, South Korea, and Taiwan. Patients with PD-L1–positive disease, defined as expression in stroma or ≥ 1% of tumor cells by immunohistochemistry, received intravenous pembrolizumab at 10 mg/kg every 2 weeks for 24 months or until progression or unacceptable toxicity. The study included 39 patients with PD-L1–positive recurrent or metastatic adenocarcinoma of the stomach or gastroesophageal junction and 32 women with metastatic PD-L1–positive triple-negative breast cancer.

Outcome in Gastric Cancer

Of 39 patients enrolled and evaluable for safety, 36 were evaluable for response on central assessment. Most patients were heavily pretreated. Median follow-up was 10.8 months.

Response was observed in eight patients (22%, 95% confidence interval [CI] = 10%–39%); all responses were partial responses. Stable disease was observed in 14%. A decrease in target lesion size was observed in 17 (53%) of 32 patients with at least one post-baseline tumor assessment.

Median time to response was 8 weeks, and median duration of response was 40 weeks (interquartile range = 40 weeks to not reached). Of eight responders, four were alive at last analysis without disease progression and with no additional anticancer therapy.

Grade 3 or 4 treatment-related adverse events were reported in five patients (13%), consisting of grade 3 fatigue in two, grade 3 pemphigoid in one, grade 3 hypothyroidism in one, grade 3 peripheral sensory neuropathy in one, and grade 4 pneumonitis in one. No treatment-related deaths were observed.

The investigators concluded: “In this population of patients with recurrent or metastatic PD-L1-positive gastric cancer, pembrolizumab had a manageable toxicity profile and promising antitumour activity, warranting further study in phase 2 and 3 trials.”

Outcome in Metastatic Triple-Negative Breast Cancer

Among the 32 women enrolled, 27 were evaluable for response. Most patients were heavily pretreated. Median follow-up was 10.0 months.

Among evaluable patients, the overall response rate was 18.5% (95% CI = 6.3%–38.1%), including complete response in one patient and partial response in four patients. Stable disease was observed in seven patients (26%).

Median time to response was 17.9 weeks, and median duration of response was not reached (range = 15.0–47.3+ weeks). Three responders remain on study and have received pembrolizumab for at least 1 year, with response durations of 24.1, 24.7, and 47.3 weeks as of last analysis.

Grade ≥ 3 treatment-related adverse events occurred in 15.6% of patients, including grade 3 anemia, aseptic meningitis, lymphopenia, headache, and pyrexia. One patient died from disseminated intravascular coagulation accompanied by grade 4 decreased blood fibrinogen, both of which were considered related to study treatment.

The investigators concluded: “This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced triple-negative breast cancer. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing.”

The study was funded by Merck & Co.

Kei Muro, MD, of the Aichi Cancer Center Hospital, Nagoya, is the corresponding author of The Lancet Oncology article.

Rita Nanda, MD, of the University of Chicago, is the corresponding author of the Journal of Clinical Oncology article.

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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