Author of

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

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

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    P3.11-027 - A randomised, open-label phase II trial of volasertib as monotherapy and in combination with standard dose pemetrexed compared with pemetrexed monotherapy in second-line non-small cell lung cancer (NSCLC) (ID 2307)

    09:30 - 09:30  |  Author(s): B. Sadrolhefazi
    • Abstract

    Background
    Polo-like kinases (Plks) are overexpressed in many cancers including NSCLC. Volasertib (BI 6727; an investigational drug) is a selective and potent Plk inhibitor, which induces mitotic arrest and apoptosis. This 3-arm trial compared the efficacy, safety and pharmacokinetics of volasertib monotherapy, volasertib combined with pemetrexed and single-agent pemetrexed as second-line therapy in patients with advanced/metastatic NSCLC (NCT00824408).

    Methods
    An initial run-in phase was conducted to determine the tolerability and dose of volasertib combined with pemetrexed 500mg/m[2]. Subsequent patients were randomised to one of three arms: (A) volasertib 300mg, (B) volasertib 300mg plus pemetrexed 500mg/m[2], or (C) pemetrexed 500mg/m[2]. Both drugs were administered on Day 1 every 21 days. Eligible patients had advanced/metastatic NSCLC, ECOG PS 0–2, adequate organ function and prior platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS) evaluated using a stratified one-sided log-rank test (Arms B versus C); an exploratory analysis was performed for Arms A versus C. Secondary endpoints included objective response rate (ORR), overall survival (OS), safety and pharmacokinetics.

    Results
    Twelve patients were included in the run-in phase; the volasertib dose selected for the randomised phase was 300mg. 131 patients were then randomised to the three arms (A: n=37, B: n=47, C: n=47). Arm A recruitment was stopped early due to an increased rate of early progression. Demographic data were balanced between the arms. One patient per arm did not receive treatment. The median number (range) of treatment cycles in Arms A, B and C was 2 (1–49), 4 (1–36) and 5.5 (1–38), respectively. Median PFS (Arms A/B/C) was 1.4/3.3/5.3 months (HR B versus C =1.141 [95% CI: 0.735–1.771; p=0.2804]; HR A versus C =2.045 [95% CI: 1.271–3.292; two-sided p=0.0030]). ORR (Arms A/B/C) was 8%/21%/9%; no complete responses were observed. Disease control rates (Arms A/B/C) were 27%/66%/68%. Median OS (Arms A/B/C) was 22.9/17.1/17.4 months. Median relative dose intensity was 100% for both volasertib and pemetrexed in all arms with a range of 80.6–111.1% in Arm A and 83.3–100.0% in Arm B for volasertib, and 87.5–100% in Arm B and 81.3–100% in Arm C for pemetrexed. The most common all-grade adverse events (AEs) were (Arms A/B/C): fatigue (56%/74%/70%), nausea (14%/48%/54%), decreased appetite (8%/44%/41%), constipation (17%/37%/22%), dyspnoea (17%/28%/30%) and vomiting (19%/33%/24%). Most common grade 3/4 AEs (>5%) were (Arms A/B/C): fatigue (8%/13%/17%), neutropenia (14%/11%/4%) and dyspnoea (3%/9% /13%). Grade 3/4 febrile neutropenia was seen in 2 (4%) patients in Arm B and 1 (2%) patient in Arm C. One fatal AE of septic shock (Arm B) was considered drug-related; 22%/22%/26% of patients experienced a serious AE. Pharmacokinetic analysis of volasertib in Arms A and B, together with historical pharmacokinetic data for pemetrexed, did not reveal any evidence of pharmacokinetic interactions between volasertib and pemetrexed.

    Conclusion
    Volasertib and pemetrexed could be combined at full single-agent doses, with generally acceptable toxicities, and demonstrated modest antitumour activity. However, the addition of volasertib did not improve PFS compared to single-agent pemetrexed in patients with relapsed or refractory NSCLC after platinum-based first-line therapy.