In a phase II clinical trial, investigators found that 42% of patients with brain metastases benefited from treatment with the immune checkpoint inhibitor pembrolizumab, with 7 of the 57 patients in the trial surviving for longer than 2 years. The study authors cautioned that these benefits must be weighed against risk of toxicity, but, overall, the results may warrant larger studies and efforts to identify patients most likely to benefit from this treatment. These findings were presented by Priscilla K. Brastianos, MD, and colleagues at the 2023 ASCO Annual Meeting (Abstract 2006) and were simultaneously published in Nature Medicine.
“There are very few effective treatments for patients with brain metastases. Our overarching objective is to find improved therapies for this patient population,” said Dr. Brastianos, of the Mass General Cancer Center. “With this trial, we investigated pembrolizumab, which is an immunotherapy for patients with brain metastases. Pembrolizumab was tolerated and showed clinical benefit in the brain in 42% of patients, which is promising for this patient population.”
Priscilla K. Brastianos, MD
Trial Details
The single-arm, open-label, phase II trial included 9 previously untreated, asymptomatic patients with brain metastases (cohort A) and 48 patients with recurrent and progressive disease after receipt of prior therapy (cohort B). Participants were enrolled in the trial between October 2016 and October 2018. The primary endpoint of the study was response rate, including complete response, partial response, or stable disease. Patients in the trial had primary tumor diagnoses that included breast, skin, non–small cell lung, small cell lung, pituitary, and other cancers.
Key Results
The research team found that 24 of the 57 patients enrolled in the trial experienced intracranial benefit with pembrolizumab, with 5 patients experiencing a complete or partial response to treatment. This included 3 patients in cohort A and 21 in cohort B—meaning the study achieved its primary endpoint.
The team also reported that median overall survival for participants was 8 months. Although the study did not have a control arm, previous studies have estimated overall survival for patients with brain metastases to be between 4 and 6 months. Seven patients in the study experienced prolonged overall survival of 2 or more years, including five patients with primary breast cancer, one patient with primary melanoma, and one patient with primary sarcoma.
The team also examined safety and tolerability of this treatment. Five patients discontinued treatment because of toxicity, and 50 of the 57 patients had one adverse event. The most frequent adverse events in patients receiving pembrolizumab were fatigue, nausea, headache, vomiting, and transaminitis (elevated levels of liver enzymes in the blood).
In terms of next steps, the research team recommends investigating biomarkers of response—especially among the study’s “exceptional responders”—that may help to predict which patients are most likely to respond to pembrolizumab. The authors noted that additional studies will be needed to identify specific facets to those patients’ tumors or tumor microenvironments that led to such a favorable response.
“Our study illustrates the promise of checkpoint inhibitors for future therapeutic strategies for brain metastases,” said Dr. Brastianos. “And our work suggests that the decision to give a checkpoint inhibitor should not be based solely on the primary tumor’s origin—it is likely there are yet-to-be determined factors that may predict response. Future studies to identify these factors may help guide, inform, and personalize treatment for patients with brain metastases.”
Disclosure: Funding for this trial was provided by Merck Sharp & Dohme, a subsidiary of Merck & Co.; the Damon Runyon Cancer Research Foundation; and the Ben and Catherine Ivy Foundation. Additional support came from the American Brain Tumor Association Basic Research Fellowship in Honor of P. Fabbri; the William G. Kaelin, Jr, Physician-Scientist Award of the Damon Runyon Cancer Research Foundation; the American Association for Cancer Research Breast Cancer Research Fellowship; the ASCO Young Investigator Award; and the National Cancer Institute. For full disclosures of the study authors, visit coi.asco.org.
