Author of

• 10743

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

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10747

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    P1.10-004 - Exploratory Subset Analysis in African Americans from the PointBreak Study (Randomized Phase 3 Pemetrexed + Carboplatin + Bevacizumab Followed by Maintenance Pemetrexed + Bevacizumab Versus Paclitaxel + Carboplatin + Bevacizumab followed by Maintenance Bevacizumab in Patients with Stage IIIB/ IV   Nonsquamous Non-Small Cell Lung Cancer) (ID 249)

    09:30 - 09:30  |  Author(s): C. Obasaju
    • Abstract

    Background
    African Americans (AA) have a higher rate of lung cancer than Caucasians per 100,000 population (74.7 versus 64.4) but are underrepresented in randomized clinical trials. In the PointBreak study, AAs were enrolled at the same rate as the US incidence of non-small cell lung cancer (NSCLC) for AAs in 2011 (13%; now 15% in 2013). Post-hoc analyses of the AA subgroup were conducted from this study to evaluate efficacy and safety, as well as these outcomes by treatment center.

    Methods
    All patients (N=939) were chemonaive with an ECOG performance status (PS) of 0/1. AAs were analyzed against Caucasians for efficacy/safety in the pemetrexed (Pem) arm only. Subgroup analyses of AAs alone were conducted for efficacy/safety (between arm comparisons) as well as academic versus community settings (pooled two treatment arms). Hazard ratios and p-values were derived from a multivariate Cox-PH model, adjusting for disease stage, gender, PS and measurable/nonmeasurable disease. Response rates and adverse events (AEs) were compared using the exact test.

    Results
    Patients had stage IIIb (with pleural effusion)/IV nonsquamous NSCLC, according to AJCC edition 6. There were 94 AAs (42 = Pem arm; 52 = Paclitaxel [Pac] arm) and 805 Caucasians in the treated population. Demographics were statistically comparable between AAs and Caucasians in the Pem Arm, respectively: 62%/53% male, 71%/53% ≤65 years, 98%/89% ever smokers, 81%/90% Stage IV disease, with ECOG PS of 0/1, 33%/67%, versus 44%/56%. Median OS was similar between AAs and Caucasians in the Pem arm at 12.4 versus 12.3 months. Median PFS for AAs and Caucasians was 4.6 months versus 6.0 months (HR 1.229 (0.864 – 1.749; p=0.251). Overall response rate (ORR) for AAs was higher, though not statistically, at 38.1% versus 33.3% (p=0.607). Efficacy among AAs was fairly similar with median OS for Pem arm at 12.4 versus 13.7 months for Pac arm (p=0.1208). Median PFS by arm was 4.6 versus 5.1 months (p=0.6699). ORR among AAs was 38% in both arms. AAs showed a heavy trend (80%) for enrollment in community centers (n=74) versus academic center (n=20). Efficacy among AAs by setting showed a higher median OS at academic sites at 16.5 months versus 11.4 months, p=0.1906 (HR=0.6605; 95% CI: 0.355 – 1.229). Median PFS was also higher at academic sites at 6.9 months versus 4.6 months, p=0.9149 (HR =0.9690; 95% CI: 0.544 – 1.726). Drug-related grade 3/4 AEs in the Pem arm showed higher percentages for Caucasians with the exception of neutropenia, as follows: anemia (7.3%/15.9%), thrombocytopenia (9.8%/25.5%), fatigue (4.9%/11.5%), neutropenia (31.7%/25.3%), febrile neutropenia (0%/1.6%). Among AAs in the Pem/Pac Arm respectively, drug-related grade 3/4 AEs were: anemia (7.3%/0%), thrombocytopenia (9.8%/4.0%), fatigue (4.9%/4.0%), neutropenia (31.7%/44.0%), and febrile neutropenia (0%/4.0%).

    Conclusion
    There were no significant differences between AAs and Caucasians for OS, PFS, and ORR. Among AAs, median OS was not superior for either arm. PFS and OS were similar for academic and community settings among AAs. Caucasians had a significantly higher incidence of Grade 3/4 thrombocytopenia (p=0.0217), but this should be interpreted with caution due to the sample size for the AAs.

  • 10776

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    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): C. Obasaju
    • 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