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Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab
Suzanne L Topalian1, Mario Sznol1, David F McDermott1
1Suzanne L. Topalian, William H. Sharfman, Julie R. Brahmer, Evan J. Lipson, Janis M. Taube, and Drew M. Pardoll, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Mario Sznol and Harriet M. Kluger, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT; David F. McDermott, Beth Israel Deaconess Medical Center; Donald P. Lawrence, Massachusetts General Hospital Cancer Center; F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA; Richard D. Carvajal, Memorial Sloan-Kettering Cancer Center, New York, NY; Michael B. Atkins, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; John D. Powderly, Carolina BioOncology Institute, Huntersville, NC; Philip D. Leming, The Christ Hospital Cancer Center, Cincinnati, OH; Igor Puzanov and Jeffrey A. Sosman, Vanderbilt University Medical Center, Nashville, TN; David C. Smith, University of Michigan, Ann Arbor, MI; and Jon M. Wigginton, Georgia D. Kollia, and Ashok Gupta, Bristol-Myers Squibb, Princeton, NJ.
Purpose:
Programmed cell death 1 (PD-1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued.
Patients And Methods:
Patients with advanced melanoma (N = 107) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival, long-term safety, and response duration after treatment discontinuation.
Results:
Median overall survival in nivolumab-treated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1- and 2-year survival rates were 62% and 43%, respectively. Among 33 patients with objective tumor regressions (31%), the Kaplan-Meier estimated median response duration was 2 years. Seventeen patients discontinued therapy for reasons other than disease progression, and 12 (71%) of 17 maintained responses off-therapy for at least 16 weeks (range, 16 to 56+ weeks). Objective response and toxicity rates were similar to those reported previously; in an extended analysis of all 306 patients treated on this trial (including those with other cancer types), exposure-adjusted toxicity rates were not cumulative.
Conclusion:
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.
Insights
Nivolumab treatment for advanced melanoma shows favorable overall survival and durable responses that persist after treatment discontinuation. Long-term safety was acceptable, with responses maintained off-therapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Programmed cell death 1 (PD-1) is an inhibitory receptor on T cells.
- PD-1 blockade can induce tumor regression in melanoma.
- The long-term impact of PD-1 blockade on survival and response durability is not fully understood.
Purpose of the Study:
- To evaluate overall survival, long-term safety, and response duration after nivolumab discontinuation in advanced melanoma patients.
- To assess the durability of responses in patients who stopped nivolumab therapy.
Main Methods:
- 107 patients with advanced melanoma received intravenous nivolumab every 2 weeks for up to 96 weeks.
- Overall survival, safety, and response duration were monitored.
- Response maintenance after treatment discontinuation was assessed.
Main Results:
- Median overall survival was 16.8 months; 1- and 2-year survival rates were 62% and 43%.
- Objective tumor regressions occurred in 31% of patients, with a median response duration of 2 years.
- Of 17 patients discontinuing therapy, 12 maintained responses off-treatment for at least 16 weeks.
Conclusions:
- Nivolumab treatment offers favorable overall survival for advanced, treatment-refractory melanoma compared to literature data.
- Responses to nivolumab are durable and can be maintained after treatment cessation.
- Nivolumab demonstrates acceptable long-term safety in advanced melanoma patients.
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