The efficacy and safety of DOCIVYX has been evaluated in patients with unresectable, locally advanced or metastatic non-small cell lung cancer whose disease has failed prior platinum-based chemotherapy or in patients who are chemotherapy naive.

Monotherapy with DOCIVYX for NSCLC Previously Treated with Platinum-Based Chemotherapy

Two randomized, controlled trials established that a DOCIVYX dose of 75 mg/m2 was tolerable and yielded a favorable outcome in patients previously treated with platinum-based chemotherapy (see below). DOCIVYX at a dose of 100 mg/m2, however, was associated with unacceptable hematologic toxicity, infections, and treatment-related mortality and this dose should not be used [see Boxed Warning, Dosage and Administration (2.7), Warnings and Precautions (5.3)].

One trial (TAX317), randomized patients with locally advanced or metastatic non-small cell lung cancer, a history of prior platinum-based chemotherapy, no history of taxane exposure, and an ECOG performance status ≤2 to DOCIVYX or best supportive care. The primary endpoint of the study was survival. Patients were initially randomized to DOCIVYX 100 mg/m2 or best supportive care, but early toxic deaths at this dose led to a dose reduction to DOCIVYX 75 mg/m2. A total of 104 patients were randomized in this amended study to either DOCIVYX 75 mg/m2 or best supportive care.

In a second randomized trial (TAX320), 373 patients with locally advanced or metastatic non-small cell lung cancer, a history of prior platinum-based chemotherapy, and an ECOG performance status ≤2 were randomized to DOCIVYX 75 mg/m2, DOCIVYX 100 mg/m2 and a treatment in which the investigator chose either vinorelbine 30 mg/m2 days 1, 8, and 15 repeated every 3 weeks or ifosfamide 2 g/m2 days 1–3 repeated every 3 weeks. Forty percent of the patients in this study had a history of prior paclitaxel exposure. The primary endpoint was survival in both trials. The efficacy data for the DOCIVYX 75 mg/m2 arm and the comparator arms are summarized in Table 15 and Figures 3 and 4 showing the survival curves for the two studies.

Only one of the two trials (TAX317) showed a clear effect on survival, the primary endpoint; that trial also showed an increased rate of survival to one year. In the second study (TAX320) the rate of survival at one year favored DOCIVYX 75 mg/m2.

Figure 3: TAX317 Survival K-M Curves - DOCIVYX 75 mg/m2 Versus Best Supportive Care

Figure 4: TAX320 Survival K-M Curves - DOCIVYX 75 mg/m2 Versus Vinorelbine or Ifosfamide Control

Patients treated with DOCIVYX at a dose of 75 mg/m2 experienced no deterioration in performance status and body weight relative to the comparator arms used in these trials.

Combination Therapy with DOCIVYX for Chemotherapy-Naive NSCLC

In a randomized controlled trial (TAX326), 1218 patients with unresectable stage IIIB or IV NSCLC and no prior chemotherapy were randomized to receive one of three treatments: DOCIVYX 75 mg/m2 as a 1-hour infusion immediately followed by cisplatin 75 mg/m2 over 30 to 60 minutes every 3 weeks; vinorelbine 25 mg/m2 administered over 6–10 minutes on days 1, 8, 15, 22 followed by cisplatin 100 mg/m2 administered on day 1 of cycles repeated every 4 weeks; or a combination of DOCIVYX and carboplatin.

The primary efficacy endpoint was overall survival. Treatment with DOCIVYX+cisplatin did not result in a statistically significantly superior survival compared to vinorelbine+cisplatin (see table below). The 95% confidence interval of the hazard ratio (adjusted for interim analysis and multiple comparisons) shows that the addition of DOCIVYX to cisplatin results in an outcome ranging from a 6% inferior to a 26% superior survival compared to the addition of vinorelbine to cisplatin. The results of a further statistical analysis showed that at least (the lower bound of the 95% confidence interval) 62% of the known survival effect of vinorelbine when added to cisplatin (about a 2-month increase in median survival; Wozniak et al. JCO, 1998) was maintained. The efficacy data for the DOCIVYX+cisplatin arm and the comparator arm are summarized in Table 16.

The second comparison in the same three-arm study, vinorelbine+cisplatin versus DOCIVYX+carboplatin, did not demonstrate superior survival associated with the DOCIVYX arm (Kaplan-Meier estimate of median survival was 9.1 months for DOCIVYX+carboplatin compared to 10.0 months on the vinorelbine+cisplatin arm) and the DOCIVYX+carboplatin arm did not demonstrate preservation of at least 50% of the survival effect of vinorelbine added to cisplatin. Secondary endpoints evaluated in the trial included objective response and time to progression. There was no statistically significant difference between DOCIVYX+cisplatin and vinorelbine+cisplatin with respect to objective response and time to progression (see Table 17).