Table 2

Clinical studies on combining or sequencing RT and anti-PD-1 checkpoint inhibition in melanoma

Author(s) (year)ICI agentStudy designnRT targetRT typeCohorts/comparatorsRT timingOS (median)PFS (median)ResponseBenefit of combination/
sequencing
Anti-PD-1
Ahmed et al (2016)45 NivolumabRetrospective26BrainStereotactic (SRS)Single cohort (RT+ICI); no comparatorConcurrent or sequential (RT before/after ICI)12.0 monthsNRNRNA
Liniker et al (2016)46 Nivolumab or pembrolizumabRetrospective53Various, including brainVarious (stereotactic and conventional)Four cohorts: RT before ICI, n=11; RT concurrent to ICI, n=16; RT at progression to ICI, n=15; WBRT, n=11Concurrent, sequential, or at progression6.4 months (RT concurrent to ICI) vs 8.6 months (RT sequential to ICI), p=0.77NRBOR in irradiated lesions 64% (RT concurrent to ICI) vs 44% (RT sequential to ICI), p=0.45; BOR in non-irradiated lesions 46% (RT concurrent to ICI) vs 52% (RT sequential to ICI), p=0.88NA
Aboudaram et al (2017)47 Nivolumab or pembrolizumabRetrospective59Various, including brainVarious (stereotactic and conventional)Two cohorts: RT+ICI, n=17; ICI, n=42Concurrent or sequential (RT before ICI)12.1 months (RT+ICI) vs 8.3 months (ICI), p=0.427.8 months (RT+ICI) vs 5.9 months (ICI), p=0.32BOR 65% (RT+ICI) vs 33% (ICI), p=0.027Yes (RT+ICI superior to ICI; BOR)
Anderson et al (2017)48 PembrolizumabRetrospective21BrainVarious (stereotactic and conventional)Single cohort (RT+ICI); no comparatorConcurrent or sequential (RT after ICI)NRNRBOR in irradiated lesions 70%NA
Pike et al (2017)49 Nivolumab or pembrolizumabRetrospective48Various, including brainVarious (stereotactic and conventional)Two cohorts: RT before ICI, n=26; RT concurrent to ICI, n=22Concurrent or sequential14.1 monthsNRNRNA
Maity et al (2018)50 PembrolizumabProspective, phase 1 (NCT02303990)24 (various tumor entities, thereof n=4 melanoma)Various, including brainVarious (stereotactic and conventional)Two cohorts: RT at progression to ICI, n=12; RT concurrent to ICI, n=12ConcurrentNRNRBOR 16.7%NA
Nardin et al (2018)51 PembrolizumabRetrospective25BrainStereotactic (SRS)Single cohort (RT+ICI); no comparatorConcurrent or sequential (RT before, concurrent to, or after ICI)15.3 months4.0 months (intracranial PFS)Local tumor control (brain) 68%NA
Roger et al (2018)52 Nivolumab or pembrolizumabRetrospective25Various, including brainStereotactic body radiation; SRS (brain)Two cohorts: RT concurrent to ICI, n=15; RT at progression to ICI, n=10Concurrent or at progression9.9 months (RT concurrent to ICI), 18.9 months (RT at progression to ICI)3.0 months (RT concurrent to ICI), 16.2 months (RT at progression to ICI)BOR 36% (all patients)NA
Trommer-Nestler et al (2018)53 Nivolumab or pembrolizumabRetrospective26BrainStereotactic (SRS)Two cohorts: RT+ICI, n=13; RT, n=13ConcurrentNRNRBOR in irradiated lesions 43% (RT+ICI) vs 20% (RT), p=0.028NA
Minniti et al (2019)44 NivolumabRetrospective35BrainStereotactic (SRS)Single cohort (RT before ICI); no comparatorSequential (RT before ICI)22.0 months10.0 months (intracranial PFS)NRNA
Knispel et al*Nivolumab or pembrolizumabRetrospective239Various, including brainVarious (stereotactic and conventional)Two cohorts: RT+ICI, n=85; ICI, n=154Sequential (RT before ICI)10.8 months (RT before ICI) vs 17.5 months (ICI), p=0.26 (adjusted for confounders)4.0 months (RT before ICI) vs 4.2 months (ICI), p=0.41 (adjusted for confounders)BOR 17% (RT before ICI) vs 25% (ICI), p=0.86 (adjusted for confounders)No (BOR, PFS, OS)
  • Published clinical studies on RT and ICI are presented with their outcomes in terms of tumor response and patient survival. Only studies investigating a cohort >20 patients are shown.

  • *Data of the present study.

  • BOR, best overall response; ICI, immune checkpoint inhibition; NA, not applicable; NR, not reported; OS, overall survival; PFS, progression-free survival; RT, radiotherapy; SRS, stereotactic radiosurgery; WBRT, whole brain radiotherapy.