Table 1.
ORR and Severe Treatment-Related AEs in Metastatic Melanoma Patients Treated with FDA-Approved Immunotherapies
| Drug | Phase | Drug and Schedule | Number of Patientsa | Objective Response Rate (%) | Treatment-Related Toxicitiesb | Reference | ||
|---|---|---|---|---|---|---|---|---|
| Any Grade (%) | Grades 3–4 (%) | |||||||
| IL-2 | ||||||||
| II | high dose IL-2 | 46 | 10 (24) | >32 (>68) | >17 (>35) | Parkinson et al. (1990) | ||
| II | high dose IL-2 | 134 | 23 (17) | 134 (100) | >78 (>37) | Rosenberg et al. (1994) | ||
| IIc | high dose IL-2 | 270 | 43 (16) | >64 (>24) | >45 (>17) | Atkins et al. (1999) | ||
| II | high dose IL-2 | 26 | 5 (19) | 26 (100) | 13 (50) | Tarhini et al. (2007) | ||
| III | low dose IL-2 | 153 | 5 (3) | N/A | 59 (39) | Agarwala et al. (2002) | ||
| III | high dose IL-2 | 93 | 6 (6) | >36 (>39) | 74 (80) | Schwartzentruber et al. (2011) | ||
| Average | (14) | (>43) | ||||||
| Anti-CTLA-4 mAbs | ||||||||
| II | ipilimumab | 57 | 9 (16) | 54 (95) | 27 (47) | Weber et al. (2009) | ||
| III | ipilimumab | 137 | 15 (11) | 105 (80) | 30 (23) | Hodi et al. (2010) | ||
| III | ipilimumab | 278 | 33 (12) | 187 (73) | 51 (20) | Robert et al. (2015a) | ||
| III | ipilimumab | 315 | 60 (19) | 268 (85) | 85 (27) | Larkin et al. (2015) | ||
| II | ipilimumab | 47 | 5 (11) | 34 (74) | 9 (19) | Hodi et al. (2016) | ||
| III | ipilimumab | 727 | 100 (14) | 324 (45) | 190 (26) | Ascierto et al. (2017) | ||
| Average | (14) | (27) | ||||||
| Anti-PD-1 mAbs | ||||||||
| I | pembrolizumab | 135 | 44 (38) | 107 (79) | 17 (13) | Hamid et al. (2013) | ||
| II | nivolumab | 107 | 33 (31) | 90 (84) | 24 (22) | Topalian et al. (2014) | ||
| I | pembrolizumab | 173 | 41 (26) | 142 (82) | 20 (12) | Robert et al. (2014) | ||
| III | nivolumab | 316 | 138 (44) | 257 (82) | 51 (16) | Larkin et al. (2015) | ||
| III | pembrolizumab | 556 | 185 (33) | 423 (76) | 65 (12) | Robert et al. (2015a) | ||
| III | nivolumab | 210 | 84 (40) | 153 (74) | 24 (12) | Robert et al. (2015b) | ||
| II | pembrolizumab | 357 | 84 (23) | 252 (76) | 45 (13) | Ribas et al. (2015) | ||
| III | nivolumab | 227 | 74 (27) | 206 (77) | 37 (14) | Larkin et al. (2018) | ||
| Average | (33) | (14) | ||||||
N/A, not available.
a
Number of patients available for ORR or treatment-related AE assessment vary across tde studies.
b
Indicated as “>” when frequency per toxicity grade was not available, and it was estimated based on tde most common treatment-related adverse event reported.
c
Data combination of eight phase II clinical trials.