Table 3.
Grade 3 or Greater TRAEs in Phase 2 Studies of Neoadjuvant Immunotherapy
| Study ID Trial Name |
No. of Pts | Neoadjuvant Therapy | TRAEs Grade ≥3 | irAEsa |
|---|---|---|---|---|
| Immunotherapy as mono therapy or dual therapy | ||||
|
NCT02927301 LCMC321,32 |
101 | Atezolizumab | 6/101 (6%) Pneumonitis: 3/101 (3%), nasal congestion: 1/101 (1%), neutropenia: 1/101 (1%), anemia: 1/101 (1%) |
All-grade preoperative immune-related TRAEs: 30/101 (30%) Rash: 12/101 (12%), infusion-related reaction: 11/101 (11%), hepatitis: 5/101 (5%), hyperthyroidism: 3/101 (3%), hypothyroidism: 1/101 (1%), pneumonitis: 1/101 (1% [the only grade 3 event]) |
|
NCT02259621 CheckMate 15914 |
22 | Nivolumab | 1/21 (5%; pneumonia) | NR |
|
NCT03158129 NEOSTAR13 |
44 | Nivolumab (N) vs. ipilimumab (I) + N | 6/44 (14%) grade 3–5 N: grade 3 pneumonia, hypoxia hypermagnesemia (each 1/23 [4%]); grade 5 pneumonitis (1/23 [4%]) NI: grade 3 diarrhea (1/21 [5%]), hyponatremia (1/21 [5%]) |
NR |
|
NCT02938624 MK3475-22324 |
15 | Pembrolizumab | 2/15 (13%) treatment-related SAEs Grade 3 myositis: 7%; grade 3 fatigue: 7% |
NR |
| ChiCTR-OIC-1701372623 | 40 | Sintilimab | 4/40 (10%) Pneumonitis: 2/40 (5%), γ-glutamyltransferase increased: 1/40 (2.5%), blood creatinine phosphokinase increased: 1/40 (2.5%), lung infection: 1/40 (2.5%) |
NR |
| Combination immunotherapy plus chemotherapy | ||||
|
NCT02716038 Columbia7 |
30 | Atezolizumab + carboplatin + nab-paclitaxel | 28/30 (93%) Increased ALT: 2/30 (7%), increased AST: 2/30 (7%), diarrhea: 1/30 (3%), anemia: 1/30 (3%), fatigue: 1/30 (3%), febrile neutropenia: 1/30 (3%), hyperglycemia: 1/30 (3%), hyponatremia: 1/30 (3%), neutropenia: 15/30 (50%), thrombocytopenia: 2/30 (7%), weight loss: 1/30 (3%) |
Possible irAEs were arthralgia or myalgia (grade 1/2; 5/30 [17%]), diarrhea (grade 1/2; 8/30 [30%]; grade 3; 1/30 [3%]), increased ALT (grade 1/2; 4/30 [13%]; grade 3; 2/30 [7%]), increased AST (grade 1/2; 3/30 [10%]; grade 3; 2/30 [7%]), hypothyroidism (grade 1/2; 3/30 [10%]), hyperglycemia (grade 4; 1/30 [3%]) |
|
NCT02572843 SAKK 16/1450 |
67 | Durvalumab + cisplatin/docetaxel | Grade ≥3 all-cause AEs during neoadjuvant treatment: Chemotherapy: 45/67 (67%) Durvalumab: 8/62 (13%) |
NR |
|
NCT01820754 TOP120122 |
13 | Ipilimumab + chemotherapy | Grade 3/4: 46% | Grade 2 pneumonitis: 1/24 (4%); grade 3 adrenal insufficiency: 4/24 (17%); diarrhea/colitis (grade 1 or 2; 6/24 [25%]; grade 3; 3/24 [13%]) |
|
NCT03081689 NADIM51 |
46 | Nivolumab + paclitaxel + carboplatin | Grade 3–5: 11/46 (24%) Neutropenia: 3/46 (7%), febrile neutropenia: 2/46 (2%), peripheral sensory neuropathy: 2/46 (4%), anorexia: 1/46 (2%), fatigue: 1/46 (2%), alopecia: 1/46 (2%), nephritis: 1/46 (2%) |
NR |
| NCT0336676652 | 13 | Nivolumab + cisplatin + pemetrexed or gemcitabine | Grade 3: 2/13 (15%) Neutropenia: 2/13 (15%), anemia: 1/13 (8%), renal dysfunction: 1/13 (8%) |
NR |
AE, adverse event; AESI, adverse event of special interest; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ID, identifier; irAE, immune-related adverse event; N, nivolumab, NI, nivolumab + ipilimumab; NR, not reported; Pt, patient; SAE, serious adverse event; TRAE, treatment-related adverse event.
a
Also termed “AESIs.”