A Phase II trial of pembrolizumab for patients with melanoma or non-small cell lung cancer and untreated brain metastases
By S. Goldberg, S. Gettinger, A. Mahajan, A. Chiang, R. Herbst, M. Sznol, A. Tsiouris, J. Cohen, A. Vortmeyer, Lucia B. Jilaveanu and 11 more. The Lancet Oncology, 2016
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Background Immunotherapy targeting the PD-1 axis has activity in several tumor types. We aimed to determine the efficacy and safety of pembrolizumab in patients with untreated brain metastases. Here we present results from a Phase II trial of the PD-1 inhibitor pembrolizumab in patients with new or progressive brain metastases from melanoma or non-small cell lung cancer (NSCLC). Methods Thirty-six patients were enrolled, 18 with melanoma and 18 with NSCLC. Patients had at least one untreated or progressive brain metastasis between 5 and 20 mm in longest diameter without associated neurologic symptoms or the need for corticosteroids. NSCLC patients had tumor tissue demonstrating PD-L1 expression. Patients were treated with pembrolizumab 10 mg/kg every two weeks until progression, and brain metastasis response was assessed every eight weeks by modified RECIST. The primary endpoint was brain metastasis response rate and the analysis was performed on an intent-to-treat basis. The trial is ongoing and here we present an early analysis. The study is registered with clinicaltrials.gov, number NCT02085070. Findings Brain metastasis response rate was 22% and 33% among patients with melanoma and NSCLC, respectively. Responses were durable, with all but one patient who responded demonstrating an ongoing response at the time of data analysis. Treatment-related serious and grade 3–4 adverse events were rare and included transaminitis, colitis, pneumonitis, fatigue, endocrine abnormalities, and acute kidney injury (1 patient each). Serious neurological adverse events included cognitive dysfunction and seizures (1 and 3 patients, respectively), due to pembrolizumab, metastases or both. Interpretation Pembrolizumab demonstrates activity in brain metastases in patients with melanoma or NSCLC with an acceptable safety profile, indicating that there may be a role for systemic immunotherapy in patients with untreated or progressive brain metastases. Funding Merck and the Yale Cancer Center.
Subfields: Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/f6b62a147fe35334b70ef84b0522223a02171833
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Citations in the corpus
- The microenvironmental landscape of brain tumors (2017, background): “Whether this also applies to patients with non-small-cell lung cancer, the most frequent source of brain metastases, is now under active investigation, and early results have been promising (Dudnik et al., 2016; Goldberg et al., 2016).”
- Melanoma Staging: Evidence-Based Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual (2017, background): “as well as stratification and analysis, are often based on the presence/absence of CNS disease.(6-20,73,74) Therefore, this additional level of granularity in the M category “maps” bet-”
- Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “There is currently limited trial data demonstrating safety and efficacy of immunotherapy in patients with small-volume untreated CNS metastases [III, B] [283].”