Table 1.
Adverse events in selected single-agent studies with ant-PD-1/PD-L1 antibodies
| Agent | First author (year) | Phase | Tumor type | No. of patients receiving anti-PD-1/PD-L1 agent (N) | Therapy schedule | Treatment-related toxicities (grade 1–5) | Treatment-related grade 3–4 toxicities |
|---|---|---|---|---|---|---|---|
| Anti-PD-1 agent | |||||||
| Nivolumab | Topalian (2012) [22] | I | NSCLC; RCC; CRC; CRPC; melanoma | 296 | 0.1–10 mg/kg every 2 weeks for up to 2 years | Total: 70% (n = 207) Fatigue (24%, n = 72) Rash (12%, n = 36) Pruritus (10%, n = 28) Pneumonitis (9%, n = 3) Infusion reaction (9%, n = 3) Hypothyroidism (2%, n = 7) |
Total: 7% (n = 22) Hypothyroidism (<1%, n = 1) Pneumonitis (1%, n = 3) Diarrhea (1%, n = 3) AST elevation (1%, n = 2) ALT elevation (1%, n = 2) Rash (1%, n = 2) Infusion reaction (<1%, n = 1) |
| Ansell (2015) [7] | I | Hodgkin's lymphoma | 23 | 3 mg/kg every 2 weeks | Total: 78% (n = 18) Rash (22%, n = 5) Thrombocytopenia (17%, n = 4) Fatigue (13%, n = 3) Pyrexia (13%, n = 3) |
Total: 22% (n = 5) Lipase elevation (4%, n = 1) Lymphopenia (4%, n = 1) MDSa (4%, n = 1) Pancreatitis (4%, n = 1) |
|
| Motzer (2014) [5] | II | RCC | 168 | 0.3, 2, or 10 mg/kg every 2 weeks | Total: 73% (n = 122) Fatigue (27%, n = 45) Rash (10%, n = 17) Pruritus (10%, n = 16) Hypothyroidism (12%, n = 10) AST elevation (5%, n = 8) ALT elevation (4%, n = 7) Pneumonitis (3%, n = 5) |
Total: 11% (n = 19) AST elevation (2%, n = 3) ALT elevation (2%, n = 3) Nausea (1%, n = 2) Hypothyroidism (<1%, n = 1) Pruritus (<1%, n = 1) Arthralgia (<1%, n = 1) |
|
| Sampson (2014) [23] | I | GBM | 20 (n = 10 single- agent arm) | Single-agent arm: 3 mg/kg every 2 weeks | Total: 60% (n = 6) Fatigue (30%, n = 3) Nausea (30%, n = 3) |
Total: 0% | |
| El-Khoueiry (2015) [8] | I/II | HCC | 47 | 0.1–10 mg/kg every 2 weeks | Total = 68% (n = 32) AST elevation (19%, n = 9) Lipase elevation (17%, n = 8) Rash (17%, n = 8) Amylase elevation (15%, n = 7) ALT elevation (15%, n = 7) |
Total = 19% (n = 9) AST elevation (11%, n = 5) ALT elevation (9%, n = 4) Lipase elevation (9%, n = 4) Fatigue (2%, n = 1) Anemia (2%, n = 1) |
|
| Gettinger (2015) [24] | I | NSCLC | 129 | 1, 3, or 10 mg/kg every 2 weeks | Total = 71% (n = 91) Fatigue (24%, n = 31) Decreased appetite (12%, n = 16) Diarrhea (10%, n = 13) Pyrexia (6%, n = 8) Pruritus (9%, n = 11) Pneumonitis (6%, n = 8) |
Total = 14% (n = 18) Fatigue (3%, n = 4) Pneumonitis (2%, n = 3) Low CD-4 cells (2%, n = 3) Diarrhea (<1%, n = 1) |
|
| Rizvi (2015) [25] | II | NSCLC (squamous) | 117 | 3 mg/kg every 2 weeks | Total = 74% (n = 87) Fatigue (33%, n = 38) Diarrhea (10%, n = 12) Rash (11%, n = 13) Pneumonitis (5%, n = 6) |
Total = 17% (n = 20) Fatigue (4%, n = 5) Diarrhea (3%, n = 3) Rash (1%, n = 1) Pneumonitis (3%, n = 4) |
|
| Weber (2015) [1] | III | Ipilimumab-refractory melanoma | 272 | 3 mg/kg every 2 weeks versus chemotherapy | Total = 67% (n = 181) Fatigue (25%, n = 67) Pruritus (16%, n = 43) Diarrhea (11%, n = 30) Nausea (9%, n = 25) |
Total = 9% (n = 24) Lipase elevation (1%, n = 3) ALT elevation (1%, n = 2) Anemia (1%, n = 2) Fatigue (1%, n = 2) |
|
| Brahmer [3] | III | NSCLC (squamous) | 131 | 3 mg/kg every 2 weeks versus docetaxel | Total = 58% (n = 76) Fatigue (16%, n = 21) Low appetite (14%, n = 11) Asthenia (10%, n = 13) Diarrhea (8% n = 10) Pneumonitis (5%, n = 6) Hypothyroidism (4%, n = 5) |
Total = 7% (n = 9) Fatigue (<1%, n = 1) Low appetite (<1%, n = 1) Leucopenia (<1%, n = 1) Pneumonitis (<1%, n = 1) Colitis (<1%, n = 1) Interstitial nephritis (<1%, n = 1) |
|
| BMS-39886 | Brahmer [26] | I | NSCLC; RCC; CRC; melanoma | 207 | 0.3–10 mg/kg every 2 weeks | Total = 61% (n = 126)b Fatigue (16%, n = 33) Infusion reaction (10%, n = 21) Diarrhea (9%, n = 19) Rash (9%, n = 14) Hypothyroidism (3%, n = 6) Adrenal insufficiency (2%, n = 3) |
Total = 5% (n = 11) Endocrine (1%, n = 2) Fatigue (<1%, n = 1) Pyrexia = 1 (<1%, n = 1) Diarrhea = 1 (<1%, n = 1) Myocarditis = 1 (<1%, n = 1) Sarcoidoisis = 1 (<1%, n = 1) |
| Pembrolizumab | Hamid (2012) [27] | I | Melanoma | 135 | 2 mg/kg every 3 weeks, or 10 mg/kg every 2 or 3 weeks | Total = 79% (n = 107) Fatigue (30%, n = 41) Rash (21%, n = 28) Pruritus (21%, n = 28) Diarrhea (20%, n = 27) |
Total = 13% (n = 17) Rash (2%, n = 3) Acute renal failure (1%, n = 2) AST elevation (1%, n = 2) Fatigue (1%, n = 2) |
| Le (2015) [10] | I | Metastatic carcinoma with or without mismatch repair deficiency | 41 | 10 mg/kg every 2 weeks | Total = 98% (n = 40) Fatigue (32%, n = 13) Diarrhea (24%, n = 10) Rash/pruritus (24%, n = 10) Hypophysitis/thyroiditis/ hypothyroidism (10%, n = 6) Pancreatitis (15%, n = 4) |
Total = 41% (n = 17) Lymphopenia (20%, n = 8) Hypoalbuminemia (10%, n = 4) Anemia (17%, n = 7) |
|
| Robert (2014) [28] | I | Ipilimumab-refractory melanoma | 173 | 2 or 10 mg/kg every 3 weeks | Total = 82% (n = 142) Fatigue (35%, n = 60) Pruritus (23%, n = 39) Rash (18%, n = 31) Diarrhea (13%, n = 22) Pneumonitis (2%, n = 3) Autoimmune hepatitis (<1%, n = 1) Hypothyroidism (4%, n = 7) |
Total = 12% (n = 20) Fatigue (3%, n = 5) Diarrhea (<1%, n = 1) Pneumonitis (<1%, n = 1) Hypophysitis (<1%, n = 1) Autoimmune hepatitis (<1%, n = 1) |
|
| Ribas (2015) [29] | II | Melanoma | 357 | 2 or 10 mg/kg every 3 weeks versus standard chemotherapy | Total = 71% (n = 252) Fatigue (26%, n = 92) Pruritus (22%, n = 79) Rash (8%, n = 29) Hypothyroidism (6% n = 22) Pneumonitis (1%, n = 3) |
Total = 13% (n = 45) Fatigue (<1%, n = 2) Myalgia (<1%, n = 2) Edema (<1%, n = 2) Colitis (<1%, n = 2) Hypophysitis (<1%, n = 2) Pneumonitis (<1%, n = 2) |
|
| Robert (2015) [2] | III | Untreated melanoma | 556 | 10 mg/kg every 2 or 3 weeks versus ipilimumab | Total = 76% (n = 423) Fatigue (20%, n = 111) Pruritus (14%, n = 79) Rash (14%, n = 77) Hypothyroidism (9%, n = 52) Hyperthyroidism (5%, n = 27) Colitis (3%, n = 15) Hepatitis (1%, n = 8) Pneumonitis (1%, n = 6) Uveitis (<0.1%, n = 4) |
Total = 12% (n = 65) Colitis (2%, n = 11) Diarrhea (n = 10) Hepatitis (n = 8) Hypophysitis (n = 2) Pneumonitis (n = 1) Type 1 diabetes (n = 1) |
|
| Garon (2015) [4] | I | NSCLC | 495 | 2 or 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks | Total = 71% (n = 351) Fatigue (19%, n = 96) Pruritus (11%, n = 53) Low appetite (11%, n = 52) Rash (10%, n = 48) Infusion reaction (3%, n = 15) Hypothyroidism (7%, n = 34) Pneumonitis (4%, n = 18) |
Total = 10% (n = 47) Dyspnea (4%, n = 19) Pneumonitis (2%, n = 9) Low appetite (1%, n = 5) Fatigue (<1%, n = 4) Infusion reaction (<1%, n = 1) |
|
| Pidilizumab | Armand (2013) [30] | II | Lymphomac | 72 | 1.5 mg/kg every 42 days × 3 doses | Total = 96% (n = 69) Neutropenia (26%, n = 19) Fatigue (25%, n = 18) Respiratory infection (19%, n = 14) Diarrhea (17%, n = 12) Thrombocytopenia (14%, n = 10) |
Total = 54% (n = 39) Neutropenia (19%, n = 14) Thrombocytopenia (8%, n = 6) |
| Anti-PD-L1 agent | |||||||
| Durvalumab | Segal [31] | I | Multiple solid tumorsa | 346 | 10 mg/kg every 2 weeks × 1 year | Total = 39% (n = 135) Fatigue (13%, n = 45) Rash (9%, n = 30) Pneumonitis (1%, n = 5) AST/ALT elevation (4%, n = 13) Hypothyroidism (2%, n = 8) |
Total = 6% (n = 20) Fatigue (1%, n = 2) Rash (<1%, n = 1) AST/ALT elevation (1%, n = 3) Hypothyroidism (<1%, n = 1) |
| Rizvi (2015) [32] | I | NSCLC | 228 | 10 mg/kg every 2 weeks × 1 year | Total = 93% (n = 213) Fatigue = 18% Low appetite = 9% Nausea = 8% Hyperthyroidism (4%, n = 9) Diarrhea (7%, n = 15) Rash (8%, n = 17) Pneumonitis (1%, n = 3) |
Total = 53% (n = 121) Diarrhea (<1%, n = 1) Rash (0%, n = 0) Hyperthyroidism (<1%, n = 1) |
|
| Atezolizumab | Herbst (2014) [33] | I | Multiple solid tumors + hematologic malignancies | 277 | 0.01–20 mg/kg every 3 weeks | Total = 70% (n = 194) Fatigue (24%, n = 67) Low appetite (12%, n = 33) Rash (11%, n = 29) Influenza-like illness (6%, n = 16) AST/ALT elevation (4%, n = 10) Tumor lysis syndrome (<1%, n = 2) |
Total = 13% (n = 35) Fatigue (2%, n = 5) Low appetite (0%, n = 0) Rash (0%, n = 0) Influenza-like illness (<1%, n = 1) AST/ALT elevation (2%, n = 6) Tumor lysis syndrome (<1%, n = 2) |
| Powles (2014) [6] | I | Urothelial carcinoma | 68 | 15 mg/kg every 3 weeks × 1 year | Total = 57% (n = 39) Low appetite (12%, n = 8) Fatigue (12%, n = 8) Pyrexia (12%, n = 8) Influenza-like illness (4%, n = 3) Thrombocytopenia (3%, n = 2) |
Total = 4% (n = 3) Asthenia (1.5%, n = 1) Thrombocytopenia (1.5%, n = 1) Phosphorus elevation (1.5%, n = 1) |
|
aMDS, myelodysplastic syndrome.
bInvestigator-reported adverse events.
cIncluded patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed indolent B-cell lymphoma
NSCLC, nonsmall-cell lung cancer; RCC, renal cell carcinoma; CRC, colorectal carcinoma; CRPC, castration-resistant prostate cancer; HCC, hepatocellular carcinoma; GBM, glioblastoma multiforme.