CLINICAL STUDIES
Combination Use with Cisplatin
The safety and efficacy of NAVELBINE in combination with cisplatin was evaluated in two randomized, multicenter trials.
Cisplatin 100mg/m
2
Study 1 was a randomized, multicenter, open-label trial of NAVELBINE plus cisplatin and cisplatin alone for the treatment of stage IV or stage IIIb NSCLC patients with malignant pleural effusion or multiple lesions in more than one lobe of the ipsilateral lung who had not received prior chemotherapy. A total of 432 patients were randomized 1:1 to receive either NAVELBINE 25 mg/m2 on Day 1 then every week of each 28-day cycle with cisplatin 100 mg/m2 administered on Day 1 of each 28-day cycle (N=214) or cisplatin 100 mg/m2 on Day 1 of each 28-day cycle (N=218).
Patient demographics and disease characteristics were similar between arms. Of the overall study population, the median age was 64 (range 33-84), 66% were male, 80% were Caucasian, 92% had stage IV disease and 8% stage IIIB, 53% had adenocarcinoma, 21% squamous cell, 14% large cell histology. The major efficacy outcome measure was overall survival. The efficacy results are presented in Table 7 and Figure 1.
Table 7. Efficacy Results (Study 1)
|
NAVELBINE plus Cisplatin |
Cisplatin Alone |
|
(N=214) |
(N=218) |
Overall Survival |
|
|
Median Survival in months (95% CI) |
7.8 (6.9, 9.6) |
6.2 (5.4, 7.7) |
Unstratified log-rank p-value |
0.01 |
|
|
Overall Response rate (ORR) Evaluable patients ORR (95% CI) |
N = 206 19% (14%, 25%) |
N=209 8% (5%, 13%) |
Chi-square test p-value |
<0.001 |
Cisplatin 120mg/m
2
Study 2 was a randomized, 3-arm, open-label, multicenter trial of NAVELBINE plus cisplatin, vindesine plus cisplatin and NAVELBINE alone for the treatment of patients with stage III or IV NSCLC who had not received prior chemotherapy. The study was conducted in Europe. A total of 612 patients were randomized 1:1:1 to receive NAVELBINE 30 mg/m2 every week of a 6-week cycle plus cisplatin 120 mg/m2 on Day 1 and Day 29, then every 6 weeks thereafter (N=206); and vindesine 3 mg/m2 for 6 weeks, then every other week thereafter plus cisplatin 120 mg/m2 on Days 1 and Day 29, then every 6 weeks thereafter (N=200) or NAVELBINE 30mg/m2 every week of a 6-week cycle (N=206). The main efficacy outcome measure was to compare overall survival between NAVELBINE plus cisplatin and vindesine plus cisplatin. The other efficacy outcome measure was to compare overall survival in the better of the two combination regimens to that of NAVELBINE alone.
Patient demographics were in general similar between arms: the median age of the overall population was 60 years (range 30 to 75), 90% were male, 78% had WHO performance status of 0 or 1. Tumor characteristics were in general similar with the exception of histologic subtype of NSCLC. Adenocarcinoma was the histologic subtype in 32% of patients in the NAVELBINE plus cisplatin arm, 40% of patients in vindesine plus cisplatin arm and 28% of patients on the NAVELBINE alone arm. Ten percent of the patients had stage IIIA disease, 28% stage IIIB and 50% stage IV. Twelve percent of the patients had received prior surgery or radiotherapy.
The efficacy results of Study 2 are presented in Table 8.
Table 8. Efficacy Results (Study 2)
|
NAVELBINE Alone |
NAVELBINE plus |
Vindesine plus |
|
(N=206) |
cisplatin (N=206) |
cisplatin (N=200) |
Median survival in
|
7.2 (5.4-9.1) |
9.2 (7.4-11.1) |
7.4 (6.1-9.1) |
months (99.5% CI)
|
|
|
|
Unstratified log-rank |
n/a1
|
0.087 |
p-value |
0.05 |
n/a |
|
Overall Response (ORR) |
|
|
|
Evaluable Patients |
N=205 |
N=203 |
N=198 |
ORR (95% CI) |
14% (10%, 20%) |
28% (22%, 35%) |
19% (14%, 25%) |
| |
|
|
Chi-square test p-value |
n/a |
0.03 |
< 0.001 |
n/a |
1n/a = not applicable
Single Agent
The safety and efficacy of NAVELBINE as a single agent was evaluated in one randomized multi-center trial.
Study 3 was a randomized, open-label clinical trial of NAVELBINE or 5-Fluorouracil (5-FU) plus leucovorin (LV) in patients with Stage IV NSCLC who had not received prior chemotherapy A total of 211 patients were randomized 2:1 to receive NAVELBINE 30 mg/m2 weekly of a 8-week cycle (N=143) or 5-FU 425 mg/m2 bolus intravenously plus LV 20 mg/m2 bolus intravenously daily for 5 days of a 4-weeks cycle (N=68).
Patient demographics and disease characteristics were in general similar between arms. In the overall population, the median age was 61 years (range 32 - 83), 74% were male, 88% were Caucasian, 46% had adenocarcinoma histology. Fifty percent of the patients had Karnofsky performance status ≥ 90 in the NAVELBINE arm compared to 38% in the 5-FU and LV arm.
The primary efficacy outcome of the study was overall survival. The median survival time was 30 weeks versus 22 weeks for patients receiving NAVELBINE versus 5-FU/LV, respectively (P=0.06). Partial objective responses were observed in 11.1% (95% CI=6.2%, 17.9%) and 3.5% (95% CI=0.4%, 11.9%) of patients who received NAVELBINE and 5-FU/LV, respectively.
|