PEMBROLIZUMAB EFFECTVE IN GASTRIC AND TRIPLE NEGATIVE BREAST CANCER

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.”