TABLE 1.
Demographic and baseline characteristics of 96 patients treated with docetaxel plus nintedanib
| Variable | N = 96 |
|---|---|
| Age, mean (years) | 59.5 (39–75) |
| Sex | |
| Male | 55 (57.3%) |
| Female | 41 (42.7%) |
| ECOG performance status | |
| 0 | 35 (36.4%) |
| 1 | 57 (59.4%) |
| 2 | 4 (4.2%) |
| Smoking status | |
| Current smokers | 56 (58.3%) |
| Never smokers | 18 (18.8%) |
| Former smokers | 18 (18.8%) |
| Unknown | 4 (4.2%) |
| Clinical stage at diagnosis | |
| Stage ≤ IIIB | 9 (9.4%) |
| Stage IIIC | 1 (1.0%) |
| Stage IV | 86 (89.6%) |
| Brain metastases | |
| Yes | 18 (18.7%) |
| No | 78 (81.3%) |
| PD-L1 expression | |
| 0% | 35 (36.5%) |
| 1–49% | 34 (35.4%) |
| ≥ 50% | 16 (16.7%) |
| Unknown | 11 (11.5%) |
| Biomarker testing | |
| EGFR mutation positive | 5 (5.2%) |
| ALK re arrangement present | 0 (0.0%) |
| ROS1 rearrangement present | 0 (0.0%) |
| KRAS mutation present | 7 (7.3%) |
| MET rearrangement present | 1 (1.0%) |
| RET rearrangement present | 3 (3.1%) |
| FGFR rearrangement present | 1 (1.0%) |
| Docetaxel plus nintedanib line | |
| Second-line therapy after first line combination ChT-ICI | 24 (25%) |
| Second-line therapy after first-line platinum-based ChT | 7 (7.3%) |
| Third-line therapy after first-line ChT and second-line ICI | 47 (49.0%) |
| Third-line therapy after first-line ICI and second-line ChT | 13 (13.5%) |
| Fourth or later-lines | 3 (3.1%) |
| Other¶ | 2 (2.1%) |
[i] ALK = anaplastic lymphoma kinase; ChT = chemotherapy; ECOG = Eastern Cooperative Oncology Group; EGFR = epidermal growth factor receptor; FGFR = fibroblast growth factor receptors; ICI = immune checkpoint inhibitor; KRAS = Kirsten ras oncogene homolog; MET = tyrosine-protein kinase Met; PD-L1 = programmed death-ligand 1; RET = Ret Proto-Oncogene; ROS1 = ROS Proto-Oncogene 1
[ii] Two patients received third-line docetaxel plus nintedanib after first-line combination ChT-ICI and second line targeted therapy (capmatinib or pralsetinib)
FIGURE 1.
Swimmer plot of treatment duration and best treatment response in EGFR-positive patients. Different colours of the horizontal bars represent different treatment lines, while the symbols at the end of each bar represent the relevant responses.
AF = Afatinib; DTX = Docetaxel; DTX_NIN = Docetaxel plus nintedanib; EGFR = epidermal growth factor receptor; ER = Erlotinib; GEM = Gemcitabine; OSM = Osimertinib; PC_CB = Paclitaxel and carboplatin; PD = progressive disease; PR = partial response; PTD_CIS = Pemetrexed and cisplatin; PTD = Pemetrexed; PTD_CB = Pemetrexed and carboplatin; SD = stable disease
TABLE 2.
Response to treatment with docetaxel plus nintedanib in all patients
| Tumor response according to RECIST version 1.1 criteria10 | All patients N = 96 |
|---|---|
| CR | 0 (0.0) |
| PR | 18 (18.8) |
| SD | 37 (38.5) |
| PD | 31 (32.3) |
| ORR (CR+PR) | 18 (18.8) |
| DCR (CR+PR+SD) | 55 (57.3) |
| Non-evaluable | 10 (10.4) |
| Median PFS, months | 3.0 (95% CI: 3–5) |
| Median OS, months | 8.0 (95% CI: 7–10) |
[i] CI = confidence interval; CR = complete response; DCR = disease control rate; ORR = objective response rate; OS = overall survival; PD = progressive disease; PFS = progression-free survival; PR = partial response; RECIST = response evaluation criteria in solid tumors; SD = stable disease
TABLE 3.
Response to treatment with docetaxel plus nintedanib in different treatment patterns
| Tumor response according to RECIST version 1.1 criteria7 | Second-line after a first-line combination ChT-ICI regimen (n = 24) | Second-line after a first-line platinum-based ChT (n = 7) | Third-line therapy following first-line ChT and second-line ICI (n = 47) | Third-line after first-line ICI and second-line ChT (n = 13) | Fourth or later-line treatment (n = 3) |
|---|---|---|---|---|---|
| CR, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| PR, n (%) | 7 (29.2) | 1 (14.3) | 9 (19.1) | 1 (7.7) | 0 (0.0) |
| SD, n (%) | 9 (37.5) | 2 (28.6) | 18 (38.3) | 7 (53.8) | 1(33.3) |
| PD, n (%) | 3 (12.5) | 3 (42.9) | 18 (38.3) | 5 (38.5) | 2(66.7) |
| ORR, n (%) | 7 (29.2) | 1 (14.3) | 9 (19.1) | 1 (7.7) | 0 (0.0) |
| DCR, n (%) | 16 (66.7) | 3 (42.9) | 27 (57.4) | 8 (61.5) | 1(33.3) |
| Non-evaluable, n (%) | 5 (20.8) | 1 (14.3) | 2 (4.3) | 0 (0.0) | 0 (0.0) |
[i] ChT = chemotherapy; CR = complete response; DCR = disease control rate; ICI = immune checkpoint inhibitor; ORR = objective response rate; PD = progressive disease; PR = partial reasponse; RECIST = response evaluation criteria in solid tumors; SD = stable disease
FIGURE 2.
(A) Progression-free survival of all patients(PFS) (n = 96) treated with nintedanib and docetaxel combination therapy. (B) Overall survival (OS) of all patients treated with nintedanib and docetaxel combination therapy. (C) Progression-free survival (PFS) of patients with and without brain metastases. (D) Median progression-free survival of patients with and without adverse events.
FIGURE 3.
Outcomes with docetaxel and nintedanib across different treatment lines. Progression-free survival (PFS) of patients receiving docetaxel plus nintedanib as second-line treatment after first-line combination chemotherapy-checkpoint inhibitors (ChT-ICI) therapy (A), third-line treatment after first-line platinum-based ChT and second-line ICI monotherapy (B), third-line treatment after first-line ICI monotherapy and second-line platinum-based ChT (C), and second-line treatment after first-line platinum-based ChT (D).
TABLE 4.
Differences in progression-free survival (PFS) and overall survival (OS) for each subset of patients according to the treatment line of docetaxel plus nintedanib
| All patients (n = 96) | Second-line after a first-line combination ChT-ICI regimen (n = 24) | Second-line after a first-line platinum-based ChT (n = 7) | Third-line therapy after first-line ChT and second-line ICI (n = 47) | Third-line after first-line ICI and (n = 13) second-line ChT | Fourth- or later-lines treatment (n = 3) | |
|---|---|---|---|---|---|---|
| Median progression-free survival, months (95% CI) | 3 (3–5) | 4 (3–8) | 2 (1–inf) | 4 (3–8) | 4 (3–inf) | 3 (0–inf) |
| Median overall survival, months (95% CI) | 8 (7–10) | 9 (6–inf) | 10 (4–inf) | 10 (8–14) | 7 (3–inf) | 8 (2–inf) |
[i] Fewer than half of a group have experienced the event
[ii] ChT-ICI = chemotherapy-checkpoint inhibitors therapy; CI = confidence interval; inf = infinity
TABLE 5.
Overview of adverse events with docetaxel plus nintedanib treatment
| Adverse Event* | All grades n (%) | Grade 3 n (%) |
|---|---|---|
| Total | 53 (55.2) | 8 (8.3) |
| Diarrhea | 29(30.2) | 1 (1.0) |
| Elevated liver enzymes | 17(17.7) | 6 (6.3) |
| Rash | 6 (6.2) | |
| Neutropenia | 4 (4.2) | |
| Peripheral neuropathy | 3 (3.1) | |
| Stomatitis | 2 (2.1) | |
| Nausea | 2 (2.1) | |
| Hypertension | 2 (2.1) | 1 (1.0) |