Author of

• 11001

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  P1.24 - Poster Session 1 - Clinical Care (ID 146)

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

  • 11003

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    P1.24-002 - Efficacy and safety of oral palonosetron compared with IV palonosetron administered with dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid tumors receiving cisplatin-based highly emetogenic chemotherapy (HEC) (ID 333)

    09:30 - 09:30  |  Author(s): G. Rizzi
    • Abstract

    Background
    Cisplatin is a cornerstone of lung cancer treatment and is associated with CINV, which impacts severely quality of life and may cause non-compliance. Palonosetron (PALO) is clinically superior and pharmacologically distinct from old-generation 5-HT3 receptor antagonists. Non-inferiority of 0.50 mg oral PALO (O-PALO) in preventing moderately emetogenic CINV when compared with 0.25 mg intravenous PALO (IV-PALO) has been demonstrated.

    Methods
    This multicenter, multinational, randomized, double-blind, parallel group study investigated the efficacy and safety of single doses of O-PALO and IV-PALO administered prior to HEC. Adult chemotherapy-naive patients with malignant solid tumors and adequate hepatic, renal and hematological function scheduled to receive cisplatin-based HEC were enrolled. Eligible patients received O-PALO (0.50 mg) or IV-PALO (0.25 mg) with oral dexamethasone (Dex) 20 mg (day 1) followed by Dex 8 mg bid (days 2–4). The primary study objective was to demonstrate the non-inferiority of O-PALO vs IV-PALO (O-vs-IV-PALO) as a percentage of patients with complete response (CR: no emesis and no rescue medication) within the acute phase (0–24 hours after chemotherapy administration). Secondary objectives included the assessment of safety and tolerability of O-vs-IV-PALO and CR in the delayed (25–120 hours) and overall (0–120 hours) phases.

    Results
    Of 743 patients randomized 1:1 to receive O-vs-IV-PALO, 739 received study medications and 738 were included in the full analysis set. The majority of patients were male (59.3%) and white (86.7%) with a median age of 59 years; 46.5% of patients had lung/respiratory tract cancer. The CR rate in the acute phase was high for both treatment groups (O-PALO 89.4%; IV-PALO 86.2%). The difference in proportions (stratum-adjusted Cochran-Mantel-Haenszel method) was 3.21% with two-sided 99% Confidence Interval (CI) from ‑2.74% to 9.17%. Non-inferiority of O-vs-IV-PALO was demonstrated since the lower limit of the 99% CI for the difference in proportions was closer to zero than the pre-defined non-inferiority margin of ‑15%. The same conclusion was obtained in the Per-Protocol population. Furthermore, results were similar with no statistically significant differences between treatment groups for delayed CR (O-PALO 76.2% vs. IV-PALO 74.8%, CMH odds ratio 1.09, 95% CI: 0.77–1.52, p=0.637) and for overall CR phases (O-PALO 73.7% vs. IV-PALO 70.2%, CMH odds ratio 1.20, 95% CI 0.87–1.67, p=0.269). Treatment-emergent adverse events (TEAEs) were reported for approximately half of all patients in each treatment arm. TEAEs related to the study drug were low (3.2% and 6.5% for O-PALO and IV-PALO respectively). Serious TEAEs related to the study drug occurred in 2 (0.5%) patients (O-PALO arm only); abdominal pain and constipation (one patient) and diarrhea and asthenia (one patient). No TEAEs related to study drug leading to discontinuation were reported.

    Conclusion
    Non-inferiority of O-PALO compared with IV-PALO was demonstrated. The results of the secondary efficacy endpoints supported the demonstration of non-inferiority based on the primary efficacy endpoint. For both O-PALO and IV-PALO the CR rate in the acute phase was >86% in patients undergoing HEC, nearly 50% of whom had lung/respiratory tract tumors. The safety profile of O-PALO and IV-PALO were comparable, with no concerns.