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

  • 10776

    +

    P1.10-033 - Safety and Resource Use in PRONOUNCE: A randomized, phase 3, open-label study of Pemetrexed plus Carboplatin with maintenance Pemetrexed (PemC) and Paclitaxel plus Carboplatin plus Bevacizumab with maintenance Bevacizumab (PCB) in patients with advanced non-squamous (NS) non-small-cell lung cancer (NSCLC) (ID 1680)

    09:30 - 09:30  |  Author(s): W.I. Ortuzar
    • Abstract

    Background
    Two combination chemotherapy regimens were compared in a Phase 3, randomized, open-label United States only study. The two-drug regimen of pemetrexed/carboplatin followed by maintenance pemetrexed (PemC) was compared to the three-drug regimen of paclitaxel/carboplatin/bevacizumab followed by maintenance bevacizumab (PCB). The primary endpoint of improved progress-free survival (PFS) without Grade 4 toxicity (G4PFS) for PemC over PCB was not met in PRONOUNCE, as reported by Zinner et al. (ASCO, 2013). No difference in PFS or overall survival (OS) for PemC vs. PCB was observed. Both regimens demonstrated tolerability, but toxicity profiles differed.

    Methods
    Patients 18+ years of age with Stage IV chemonaïve non-squamous non-small-cell lung cancer (NS-NSCLC) were randomized to PemC (n=182) or PCB (n=179). Safety data were compared for patients who received ≥1 dose of study treatment (PemC:171; PCB:166), and resource use including concomitant medications, transfusions, and hospitalizations was recorded. Measures were compared between arms using Fisher’s exact test, if not otherwise specified. Protocol-defined chemotherapy infusion time was 0.7 hours for PemC and 4-5 hours for PCB. For the primary endpoint of G4PFS, the G4 events were reported regardless of drug causality.

    Results
    Of 152 G4PFS events for PemC, 37 (24.3%) resulted from first occurrence of a G4 event. Of 144 G4PFS events for PCB, 64 (44.4%) resulted from first occurrence of a G4 event. The safety profile for the entire study demonstrated that patients on PemC experienced significantly more drug-related Grade 3/4 anemia (18.7% vs. 5.4%; p<0.001), Grade 3/4 thrombocytopenia (24.0% vs. 9.6%; p<0.001), and Grade 1/2 nausea (46.8% vs. 28.9%; p<0.001). Patients on PCB experienced significantly more drug-related Grade 3/4 neutropenia (24.6% vs. 48.8%; p<0.001) and Grade 1/2 alopecia (8.2% vs. 28.3%; p<0.001). There was a significantly higher rate of drug-related Grade 1/2 sensory neuropathy (8.2% vs. 30.1%; p<0.001), Grade 1/2 hypertension (0.0% vs. 9.6%; p<0.001), Grade 1/2 hemorrhage in pulmonary/upper respiratory (1.8% vs. 13.3%; p< 0.001) and Grade 1/2 joint pain (1.8% vs. 13.9%; p<0.001) with PCB. Patients on PemC required more red blood cell (RBC) transfusions (34.5% vs. 11.4%; p<0.001), but there was no difference in platelet transfusions (p=0.621). Erythropoietic stimulating agents (ESAs) were used more frequently (19.9% vs. 7.2%; p<0.001) in PemC, and granulocyte colony-stimulating factor (G-CSF) use was significantly higher with PCB (17.0% vs. 30.1%; p=0.005). Requirement for antibiotics (p=0.323) and antiemetics (p=0.574) did not differ between PemC and PCB. There were no differences between PemC and PCB in the number of patients with at least one hospitalization (34.5% vs. 31.9%; p=0.645), and the mean length of stay between PemC (8.2d +/- 6.79) and PCB (8.8d +/- 7.33) did not differ (p=0.682;Wilcoxon rank sum test).

    Conclusion
    The toxicity profiles of PemC and PCB were consistent with previous reports. Toxicities documented as important to patients were split, with mild-to-moderate nausea more common for PemC and alopecia, infection and neuropathy more frequent for PCB. Resource intense toxicities were also divided. Hospitalizations did not differ between treatments. ESAs and RBC transfusions were more common with PemC, and G-CSF use was more common with PCB. ClinicalTrials.gov identifier:NCT00948675