Table 1.
Author, year |
Trial phase |
Indication | Number exposed |
Drug/s | Dose | Arthralgia | Arthritis | Dry eyes | Dry mouth |
Myalgia | Muscle weakness |
Vasculitis | Other |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Anti-CTLA-4 | |||||||||||||
Bashey 2009 |
1 | Relapse after hematopoetic stem cell transplant |
29 | Ipilimumab | Dose escalation |
NR | 2 (7%) | NR | NR | NR | NR | NR | “bone pain”: 1 (3%); “muscle cramps”: 1 (3%) |
Downey 2007 |
2 | Metasatic melanoma |
139 | Ipilimumab (+/− peptide vaccine) |
3 mg/kg in one group, dose escalation in other |
10/73 (13.7%) with peptide; 4/66 (without peptide |
NR | NR | NR | NR | NR | NR | NR |
Hersh 2014 |
2 | Advanced melanoma |
72 | Ipilimumab +/− dacarbazine |
3 mg/kg | NR | NR | NR | NR | NR | NR | 1/35 (3%) in ipi + dacarbazine |
NR |
Hodi 2014 (1) Cancer Immunol Res |
1 | Metasatic melanoma |
46 | Ipilimumab +/− bevacizumab |
3 mg/kg or 10 mg/kg |
13 (28%) “joint pain” |
NR | 2 (4%) | NR | 6
(13%) “muscle pain” |
NR | 1 (2%) with GCA |
“joint function” problems: 1 (2%) |
Hodi 2014 (2) JAMA* |
2 | Metasatic melanoma |
245 | Ipilimumab +/− sargramostim |
10 mg/kg | 3/118 (3%) in combination; 1/120 (1%) in ipi alone |
1/118 (1%) in combination |
NR | NR | 2/118
(2%) combinatio n; 4/120 (3%) ipi alone |
1/118 (1%) combinati on; 1/120 (1%) ipi alone |
NR | “autoimmune disease”: 4/120 (3%) in Ipi alone |
Kwon 2014 |
3 | Metastatic prostate cancer |
399 | Ipilimumab + radiation |
10 mg/kg | 44/393 (11%) | NR | NR | NR | NR | NR | NR | MSK pain: 32 (8%) |
Le 2013 |
1 | Pancreatic cancer | 30 | Ipilimumab +/− GVAX |
10 mg/kg | Ipi + GVAX: 1/15 (75) |
NR | Ipi: 1/15 (7%) |
NR | NR | NR | NR | NR |
Lynch 2012 |
3 | NSCLC | 138 | Ipilimumab
+ carboplatin, paclitaxel (concurrent or phased) |
10 mg/kg | Concurrent: 16/71, (22.5%) phased: 12/67 (18%) |
NR | NR | NR | NR | NR | NR | NR |
Merchant 2015 |
1 | Advanced solid tumors (pediatric) |
33 | Ipilimumab | Dose escalation |
NR | NR | NR | NR | 1/33 (3%) | NR | NR | NR |
Prieto 2012* |
1/2 | Metastatic melanoma |
177 | Ipi + peptide vaccine; Ipi + IL- 2, Ipi dose escalation + peptide vaccine |
various | NR | 1/36 (3%) in Ipi + IL-2; 1/85 (1%) in Ipi DE + peptide vaccine |
NR | NR | NR | NR | NR | NR |
Reck 2013 | 2 | Extensive disease small cell lung CA |
85 | Ipilimumab + chemotherapy, concurrent or phased |
10 mg/kg | 24% in concurrent; 46% in phased |
NR | NR | NR | NR | NR | NR | NR |
Robert 2011 |
Metastatic melanoma |
247 | Ipilimumab + dacarbazine |
NR | NR | NR | NR | NR | NR | NR | NR | Back pain 28/247 (11.3%) |
|
Sarnaik 2010 |
2 | Stage III/IV melanoma |
75 | Ipilimumab + peptide vaccine |
3 mg/kg, 10 mg/kg |
Arthritis/arthralgia 17/75 (23%) |
2/75 (3%) |
NR | Myositis/ myalgia 16/75 (21%) |
NR | NR | NR | |
Weber 2008* |
1/2 | Metastatic melanoma |
88 | Ipilimumab | Various | 1/88 (1%) | NR | NR | NR | NR | NR | NR | Pain in extremity: 1/88 (1%) |
Yamazaki 2015 |
2 | Previously untreated advanced melanoma |
15 | Ipilimumab + dacarbazine |
10 mg/kg | NR | NR | NR | NR | NR | NR | NR | Back pain: 4/15 (27%) |
Yang 2007 | 2 | Metastatic RCC | 47 | Ipilimumab | Various | 1/47 (2%) | NR | NR | NR | NR | NR | NR | NR |
Calabro 2014 |
2 | Malignant mesothelioma |
29 | Tremelimumab | Dose escalation |
4 (14%) | NR | NR | NR | NR | NR | NR | NR |
Ralph 2010 |
2 | Advanced gastric and esophageal adenocarcinoma |
18 | Tremelimumab | 15 mg/kg | 3/18 (17%) | NR | NR | NR | NR | NR | NR | NR |
Sangro 2013 |
2 | HCC and hepatitis C |
21 | Tremelimumab | 15 mg/kg | NR | 1/21 (5%) | NR | NR | NR | NR | NR | NR |
Anti-CTLA-4 vs. Anti-PD-1 | |||||||||||||
Robert 2015 (2) Pembro |
3 | Advanced melanoma |
811 | Ipilimumab vs. Pembrolizumab |
Pembro: 10 mg.kg Ipi: 3 mg/kg |
26/278 (9%) in q2week Pembro, 32/277 (12%) in q3week Pembro, 13/256 (5%) in Ipi |
5/278 (2%) in q2week, 1/277 (.450 in q2week |
MR | 20/278 (8%) in q2week pembro, 11/277 (4%) in q3week pembro, 1/2576 (.4%) in ipi |
19/278 (7%) in q2week, 6/277 (2%) in q3week, 2/256 (2%) in ipi |
NR | NR | Myositis: 2/277 (1%) in q3week, 1/256 (0.5%) in Ipi MSK stiffness: 3/278 (1%) in q2week, 2/277 (1%) in q3week |
Anti-PD-1 | |||||||||||||
Borghaei 2015 |
3 | NSLC | 287 | Nivolumab | 3 mg/kg | 46 (16%) | NR | NR | NR | 18 (6%) | NR | NR | MSK pain: 39 (14%) |
Brahmer 2010 |
1 | Refractory solid tumors |
39 | Nivolumab | Dose escalation |
2 (5%) | NR | NR | NR | NR | NR | NR | MSK “events”: 6 (15%) |
Brahmer 2015 |
3 | Squamous cell lung CA |
135 | Nivolumab | 3 mg/kg | 7 (5%) | NR | NR | NR | 2 (2%) | NR | NR | NR |
Gibney 2014 |
1 | Resected metastatic melanoma |
33 | Nivolumab + peptide vaccine |
Dose escalation |
14 (43%) | NR | NR | 8 (24%) | 6 (18%) | 4 (12%) | NR | “eye disorders” (e.g. dry eyes) 8 (24%) |
Motzer 2015 |
2 | Metastatic renal cell carcinoma |
168 | Nivolumab | 3 doses: 0.3 mg/kg, 2 mg/kg, 10 mg/kg |
1/60 (2%) in 0.3 mg/kg; 4/54 (7%) in 2 mg/kg; 8/54 (15%) in 10 mg/kg |
NR | NR | 0.3mg/kg : 2/60 (3%) in, 2 mg/kg 3/54 (6%), 10 mg/kg 6/54 (11%) |
NR | NR | NR | NR |
Rizvi 2015 | 2 | Squamous NSCLC | 117 | Nivolumab | 3 mg/kg | NR | NR | NR | 7/117 (6%) |
6/117 (5%) | NR | NR | NR |
Robert 2015 (1) Nivo |
3 | Previously untreated stage III or IV melanoma |
206 | Nivolumab | 3 mg/kg | 12/206 (6%) | NR | NR | NR | 9/206 (4%) | NR | NR | Pain in extremity: 6/206 (3%) |
Weber 2015 |
3 | Advanced melanoma progressed after anti-CTLA-4 |
268 | Nivolumab | 3 mg/kg | 14/268 (5%) | NR | NR | NR | NR | NR | NR | NR |
Ribas 2015 |
2 | Ipilimumab refractory melanoma |
357 | Pembrolizumab | 2 mg/kg, 10 mg/kg |
13/178 (7%) in lower; 11/179 (6%) in higher |
NR | NR | NR | 9/178 (5%) in lower, 7/179 (4%) in higher |
NR | NR | NR |
Robert 2014* |
1 | Metastatic melnaoma |
173 | Pembrolizumab | 2 mg/kg, 10 mg/kg |
NR | NR | NR | NR | NR | 1/89 (1%) in 2 mg/kg group |
NR | MSK pain: 1/84 (1%) in 10 mg/kg group |
Anti-PD-L1 | |||||||||||||
Brahmer 2012 |
1 | Advanced cancers |
207 | MDX-1105 | Dose escalation |
15 (7%) | NR | NR | NR | NR | NR | NR | Sarcoid: 1 (0.5%) |
Combination Anti-CTLA-4 and Anti-PD-1 | |||||||||||||
Larkin 2015 |
3 | State III or IV melanoma |
945 | Ipilimumab, Nivolumab or combination |
3 mg/kg ipi, 3 mg/kg nivo, 3 mg/kg ipi + 1 mg/kg nvo |
Nivo: 24/313 (7.7%), Ipi 19/311 (6.1%), both 33/313 (10.5%) |
NR | NR | NR | NR | NR | NR | NR |
Postow 2015 |
1 | Metastatic melanoma |
142 | Ipilimumab +/− Nivoluamb |
Dose escalation |
10/94 (10%) in combined, 4/46 (9%) in Ipi |
NR | NR | NR | 9/94 (10%) combined; 6/46 (13%) in Ipi |
NR | NR | NR |
NR: Not reported, Ipi: Ipilimumab, DE: dose escalation, Pembro: Pembrolizumab, Nivo: Nivolumab
: Only reported grade 3 or higher adverse events.