Author of

• 10743

  +

  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10787

    +

    P1.10-044 - nab-Paclitaxel in combination with carboplatin as first-line therapy in diabetic patients with advanced non-small cell lung cancer (NSCLC) (ID 2446)

    09:30 - 09:30  |  Author(s): S. Owen
    • Abstract

    Background
    Diabetes and other age-related comorbidities frequently occur together in patients with NSCLC and may affect treatment efficacy and tolerability. Several studies demonstrated that diabetic patients have worse outcomes than those without diabetes. Additionally, studies have suggested that metformin may enhance the effects of chemotherapy, leading to improved outcomes. In a phase III trial, nab-paclitaxel (nab-P, 130 nm albumin-bound paclitaxel particles) + carboplatin (C) significantly improved the primary endpoint of overall response rate (ORR) from 25% to 33% (P = 0.005), with a trend toward improved overall survival (OS) and progression-free survival (PFS) vs solvent-based paclitaxel (sb-P) + C in patients with advanced NSCLC. This exploratory analysis examined efficacy and safety outcomes in diabetic patients with advanced NSCLC.

    Methods
    Patients with untreated stage IIIB/IV NSCLC were randomized 1:1 to nab-P 100 mg/m[2] on d 1, 8, 15 or sb-P 200 mg/m[2] d 1 q21d; both arms received C AUC 6 d 1 q21d. ORR and PFS were determined by blinded, centralized review. P values for ORR were based on chi-square test, and those for OS and PFS were based on log-rank test. Multiple sensitivity analyses were performed to confirm treatment differences and to rule out confounding effects from other baseline covariates.

    Results
    31 patients in the nab-P/C and 30 patients in the sb-P/C arms were included in this analysis. Similar to the intent-to-treat (ITT) population, most diabetic patients were male (75%), white (62%), with ECOG PS 1 (79%), and stage IV disease (85%). In these patients, ORR for nab-P/C vs sb-P/C was 52% vs 27% (response rate ratio 1.935; P = 0.046), median PFS was 10.9 vs 4.9 months (HR 0.416; P = 0.016), and median OS was 17.5 vs 11.1 months (HR 0.553; P = 0.057). Treatment difference in PFS remained significant (P ≤ 0.026) after adjusting for baseline characteristics (including histology, region, stage, and age). For OS, region, stage, race, and age were not observed to be confounding factors on treatment effect. Metformin was concomitantly used in 29% and 37% of diabetic patients in the nab-P/C vs sb-P/C arms, respectively. The percentage of patients experiencing ≥ 1 adverse event (AE) was similar between the diabetic and ITT populations. Among diabetic patients, the most common grade 3/4 AEs in the nab-P/C vs sb-P/C arms were neutropenia (53% vs 55%), anemia (23% vs 10%), peripheral neuropathy (PN, 7% vs 23%), thrombocytopenia (20% vs 7%), and fatigue (7% vs 10%); differences were not statistically significant. Safety findings were similar to those observed in the ITT population; however, the incidence of grade 3/4 PN was slightly higher for both arms in the diabetic population compared with the ITT population (for nab-P/C vs sb-P/C, 3% vs 12%; P < 0.001).

    Conclusion
    In this analysis, nab-P/C demonstrated improved efficacy and was well tolerated in diabetic patients with advanced NSCLC. These findings warrant further study in a larger diabetic patient population. The relationship between the efficacy of nab-P and glucose level/metformin use also merits additional study.