Introduction
Materials and methods
Study design and patients
Procedures
Evaluation of appropriate starting dose
Outcomes
Criteria |
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CTCAE grade ≥ 3 non-hematologic toxicity (except transient electrolyte abnormality and isolated increase of GGT) Gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, abdominal pain) despite adequate supportive care |
CTCAE grade 4 hematological toxicity Decreased neutrophil count (not associated with fever ≥ 38.5 °C) for > 7 days, despite adequate supportive treatment (e.g., G-CSF) Decreased WBC count for > 7 days, despite adequate supportive treatment (e.g., G-CSF) |
CTCAE grade 4 febrile neutropenia associated with fever ≥ 38.5 °C |
CTCAE grade ≥ 2 ALT and/or increased AST in conjunction with CTCAE grade ≥ 2 increase of total bilirubin |
Inability to resume nintedanib dosing within 14 days after stopping because of toxicity |
Statistical analysis
Results
Patient demographics
Nintedanib 200 mg with docetaxel 75 mg/m2 | |
---|---|
Number of patients, N (%) | 10 (100.0) |
Gender, n (%) | |
Male | 2 (20.0) |
Female | 8 (80.0) |
Age (years) | |
Median (min–max) | 69 (55–75) |
BSA (m2) | |
Median (min–max) | 1.45 (1.41–1.48) |
Body weight (kg) | |
Median (min–max) | 48.40 (40.8–51.9) |
Height (cm) | |
Median (min–max) | 155.5 (151–165) |
Smoking status, n (%) | |
Never smoked | 8 (80.0) |
Ex-smoker | 2 (20.0) |
Currently smokes | 0 (0.0) |
ECOG PS, n (%) | |
0 | 4 (40.0) |
1 | 6 (60.0) |
Metastatic disease at screening, n (%) | |
No | 0 (0.0) |
Yes | 10 (100.0) |
Number of metastatic sites | |
Median (min–max) | 1.00 (1.0–3.0) |
Best response to first-line, platinum-based chemotherapy, n (%) | |
CR/PR/SD | 7 (70.0) |
PD | 1 (10.0) |
Not applicable/unknown | 2 (20.0) |
EGFR mutation status, n (%) | |
Negative | 6 (60.0) |
Positive | 4 (40.0) |
ALK mutation status, n (%) | |
Positive | 0 (0.0) |
Negative | 7 (70.0) |
Unknown | 3 (30.0) |
Exposure to study drug
DLTs
Patient | Nintedanib dose at onset of AE (mg) | Grade and preferred term | Cycle |
---|---|---|---|
Patients who experienced DLTs in cycle 1 (with or without DLTs after cycle 1) | |||
1 | 200 bid | Grade 3 increase in ALT, grade 3 increase in AST and grade 2 hyperbilirubinemia | Cycle 1 |
150 bid | Grade 3 increase in ALT, grade 3 increase in AST and grade 2 hyperbilirubinemia | After cycle 1 | |
2 | 200 bid | Grade 3 increase in ALT and AST | Cycle 1 |
Patients who experienced DLTs only after cycle 1 | |||
3 | 200 bid | Grade 3 increase in AST | After cycle 1 |
4 | 200 bid | Grade 3 increase in ALT | After cycle 1 |
Safety
System organ class/preferred term | Nintedanib 200 mg with docetaxel 75 mg/m2 | |
---|---|---|
All grades
N (%) | Grade 3/4
N (%) | |
Number of patients | 10 (100.0) | 10 (100.0) |
Total with any AEs | 10 (100.0) | 10 (100.0) |
Blood and lymphatic system disorders | 2 (20.0) | 2 (20.0) |
Febrile neutropenia | 2 (20.0) | 2 (20.0) |
Eye disorders | 5 (50.0) | 0 (0.0) |
Lacrimation increased | 2 (20.0) | 0 (0.0) |
Gastrointestinal disorders | 9 (90.0) | 0 (0.0) |
Constipation | 5 (50.0) | 0 (0.0) |
Diarrhea | 5 (50.0) | 0 (0.0) |
Nausea | 5 (50.0) | 0 (0.0) |
Vomiting | 2 (20.0) | 0 (0.0) |
General disorders and administration-site conditions | 8 (80.0) | 0 (0.0) |
Fatigue | 4 (40.0) | 0 (0.0) |
Edema peripheral | 3 (30.0) | 0 (0.0) |
Pyrexia | 3 (30.0) | 0 (0.0) |
Malaise | 2 (20.0) | 0 (0.0) |
Infections and infestations | 6 (60.0) | 0 (0.0) |
Cystitis | 2 (20.0) | 0 (0.0) |
Upper respiratory tract infection | 2 (20.0) | 0 (0.0) |
Investigations | 10 (100.0) | 10 (100.0) |
Neutrophil count decreased | 10 (100.0) | 10 (100.0) |
WBC count decreased | 10 (100.0) | 10 (100.0) |
ALT increased | 8 (80.0) | 3 (30.0) |
AST increased | 7 (70.0) | 3 (30.0) |
GGT increased | 4 (40.0) | 2 (20.0) |
Blood alkaline phosphatase increased | 2 (20.0) | 0 (0.0) |
Hemoglobin decreased | 2 (20.0) | 0 (0.0) |
Lymphocyte count decreased | 2 (20.0) | 2 (20.0) |
Metabolism and nutrition disorders | 4 (40.0) | 1 (10.0) |
Decreased appetite | 4 (40.0) | 0 (0.0) |
Musculoskeletal and connective tissue disorders | 2 (20.0) | 0 (0.0) |
Myalgia | 2 (20.0) | 0 (0.0) |
Nervous system disorders | 5 (50.0) | 0 (0.0) |
Peripheral sensory neuropathy | 4 (40.0) | 0 (0.0) |
Dysgeusia | 3 (30.0) | 0 (0.0) |
Headache | 2 (20.0) | 0 (0.0) |
Psychiatric disorders | 3 (30.0) | 0 (0.0) |
Insomnia | 3 (30.0) | 0 (0.0) |
Skin and subcutaneous tissue disorders | 9 (90.0) | 0 (0.0) |
Alopecia | 9 (90.0) | 0 (0.0) |
Palmar–Plantar erythrodysesthesia syndrome | 2 (20.0) | 0 (0.0) |
Pruritus | 2 (20.0) | 0 (0.0) |
Rash | 2 (20.0) | 0 (0.0) |
Vascular disorders | 4 (40.0) | 1 (10.0) |
Flushing | 2 (20.0) | 0 (0.0) |