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ABSTRACT: Purpose
Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab.Patients and methods
We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma metastasis that would benefit from palliative RT and one metastasis that would not be irradiated. Nivolumab 1 mg/kg + ipilimumab 3 mg/kg and extracranial RT with a dose of 30 Gy in 10 fractions was administered in Cohort A, and then 27 Gy in 3 fractions was administered in Cohort B. The primary outcome was safety.Results
Twenty patients were treated (10 in each cohort). The rates of treatment-related grade 3-4 adverse events in Cohort A and B were 40% and 30%, respectively. There were no grade ?3 adverse events attributed to RT. Patients responded to treatment outside of the irradiated volume (Cohort A 5/10; Cohort B 1/9). No evaluable patients had progression of irradiated metastases. Immunologic changes were seen in the peripheral blood with increases in T-cell receptor diversity in some responding patients.Conclusions
RT with nivolumab and ipilimumab was safe compared with historical data of nivolumab and ipilimumab alone. Immunologic effects were observed in the peripheral blood. Randomized studies are ongoing to assess whether RT increases the efficacy of nivolumab and ipilimumab.
SUBMITTER: Postow MA
PROVIDER: S-EPMC7959513 | biostudies-literature | 2020 Jul
REPOSITORIES: biostudies-literature
Postow Michael A MA Knox Susan J SJ Goldman Debra A DA Elhanati Yuval Y Mavinkurve Vikram V Wong Phillip P Halpenny Darragh D Reddy Sunil K SK Vado Kenya K McCabe Danielle D Ramirez Kristen Aufiero KA Macri Mary M Schwarzenberger Paul P Ricciardi Toni T Ryan Aileen A Venhaus Ralph R Momtaz Parisa P Shoushtari Alexander N AN Callahan Margaret K MK Chapman Paul B PB Wolchok Jedd D JD Subrahmanyam Priyanka B PB Maecker Holden T HT Panageas Katherine S KS Barker Christopher A CA
Clinical cancer research : an official journal of the American Association for Cancer Research 20200323 13
<h4>Purpose</h4>Preclinical data suggest that radiotherapy (RT) is beneficial in combination with immune checkpoint blockade. Clinical trials have explored RT with single-agent immune checkpoint blockade, but no trials have reported RT with the combination of nivolumab and ipilimumab.<h4>Patients and methods</h4>We conducted a phase 1 study of patients with stage IV melanoma receiving nivolumab and ipilimumab with two different dose-fractionation schemes of RT. Patients had at least one melanoma ...[more]