Durable Tumor Responses With Nivolumab in Long-Term Follow-up of Patients With Advanced Melanoma
In a dose-escalation, cohort expansion study reported in the Journal of Clinical Oncology, Topalian et al found that treatment with the PD-1 immune checkpoint inhibitor nivolumab produced durable responses in patients with advanced melanoma. Long-term follow-up also showed promising survival rates and acceptable toxicity.
Study Details
In the study, 107 patients with melanoma initiated treatment with nivolumab from November 2008 through January 2012. Nivolumab was given intravenously every 2 weeks in an outpatient setting in 8-week treatment cycles at 1, 3, or 10 mg/kg during dose escalation. After completion of dose escalation, each dose cohort was expanded and, after protocol amendment, additional patients were randomly assigned to receive doses of 0.1, 0.3, and 1.0 mg/kg.
Treatment continued for up to 96 weeks. Overall, 62% of patients had received at least two prior systemic treatments for melanoma, 78% had visceral metastases, and 36% had increased lactate dehydrogenase levels.
Response Duration and Survival
Patients were followed from 14 months to 4.3 years after the start of treatment. The objective response rate was 31% in all patients, including rates of 35%, 28%, 31%, 41%, and 20% at doses of 0.1 (n = 17), 0.3 (n = 18), 1.0 (n = 35), 3 (n = 17), and 10 mg/kg (n = 20).
Among the 33 patients with objective response, median duration of response was 104 weeks. Among 17 patients discontinuing therapy for reasons other than disease progression, 12 (71%) maintained responses off therapy for ≥ 16 weeks (range, 16–56+ weeks). Among all patients, median progression-free survival was 3.7 months and median overall survival was 16.8 months, with 1- and 2-year survival rates of 62% and 43%.
Toxicity
The maximum-tolerated dose of nivolumab was not reached. The most common adverse events of any grade were fatigue (32%), rash (23%), and diarrhea (18%). Grade 3 or 4 treatment-related adverse events occurred in 22% of patients, with the most common being lymphopenia (3%) and fatigue, diarrhea, and abdominal pain (2% each).
Treatment-related adverse events of any grade with potential immune-related causality occurred in 54% of patients, with the most common being skin disorders (36%), gastrointestinal events (18%), and endocrinopathies. Grade 3 or 4 adverse events in this category occurred in 5% of patients.
The investigators concluded, “Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Long-term safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma.”
Suzanne L. Topalian, MD, of Johns Hopkins University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Bristol-Myers Squibb and Ono Pharmaceutical Company. For full disclosures of the study authors, visit jco.ascopubs.org.
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®.
