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K. Hagan



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    P2.11 - Poster Session 2 - NSCLC Novel Therapies (ID 209)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.11-005 - Randomized Phase II Study of Pemetrexed v. Pemetrexed/Bevacizumab v. Carboplatin/Pemetrexed/Bevacizumab in Patients with Previously Untreated Advanced Non-Squamous Non-Small-Cell Lung Cancer and Poor Performance Status (ID 894)

      09:30 - 09:30  |  Author(s): K. Hagan

      • Abstract

      Background
      Pemetrexed (Pem) and bevacizumab (Bev) have each been shown to improve survival in patients (pts) with advanced non-squamous non-small-cell lung cancer (NSCLC) (Scagliotti JCO 2008, Sandler NEJM 2006). Recent evidence suggests these agents can be safely combined and given with carboplatin (Cb) in the first-line setting with encouraging activity (Patel, ASTRO 2012). However, the efficacy and safety of these agents in pts with poor performance status (PS) are unknown. Herein, we report a prospective randomized phase II study of first-line pem v. pem/bev v. cb/pem/bev in pts with advanced NSCLC and poor PS.

      Methods
      Key eligibility included: pts with newly diagnosed advanced non-squamous NSCLC (IIIB or IV), an Eastern Cooperative Oncology Group (ECOG) PS of 2, and measurable disease per RECIST v.1.1. Pts were randomized 1:1:1 to receive either Pem 500mg/m[2] IV (Arm 1), Pem 500mg/m[2] IV and Bev 15mg/kg IV (Arm 2), or Pem 500mg/m[2] IV, Bev 15mg/kg IV, and Cb AUC=5 IV (Arm 3). Cycles were 21 days, with reimaging every 2 cycles. Pts on Arm 3 received a maximum of 4 cycles (12 weeks) of Cb. All pts continued Pem or Pem/Bev until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety.

      Results
      Between June 2009 and May 2013, 155 pts were randomized. Summary demographic data are available for 142 pts (median age: 72 years, adenocarcinoma, 80%, males, 59%) in Arms 1, 2, and 3; 97%, 98%, and 88% of pts were current or former smokers, respectively. The most common treatment-related grade 3/4 toxicities are presented below. ORRs for Arms 1, 2, and 3 were 15%, 24%, and 40%, respectively. While modest efficacy was observed in Arm 1, recent data (Lilenbaum, et al. 2012) suggesting a significant OS advantage in pts receiving Pem in combination with Cb vs. Pem alone led to closure of this arm in early 2013. A subset analysis examining pts older or younger than 70 years found that the younger population treated on Arm 1 had inferior ORRs to older pts treated on Arm 3 (7% v. 26%, respectively).

      Grade 3/4 Toxicity Arm 1 (N=48) Arm 2 (N=49) Arm 3 (N=45)
      Hematologic
      Hemoglobin 5 (10%) 1 (2%) 5 (11%)
      Leukocytes 0 1 (2%) 4 (9%)
      Neutrophils 3 (6%) 4 (8%) 8 (18%)
      Platelets 0 2 (4%) 10 (22%)
      Non-hematologic
      Anorexia 1 (2%) 0 0
      Cardiac ischemia/infarction 0 1 (2%) 0
      CNS ischemia 0 1 (2%) 1 (2%)
      Deep vein thrombosis 0 1 (2%) 1 (2%)
      Dehydration 2 (4%) 2 (4%) 0
      Diarrhea 0 2 (4%) 1 (2%)
      Dyspnea 0 2 (4%) 2 (4%)
      Fatigue 10 (21%) 9 (18%) 9 (20%)
      Epistaxis 0 1 (2%) 0
      Hypertension 0 2 (4%) 2 (4%)
      Muscle weakness 4 (8%) 3 (6%) 4 (9%)
      Nausea 0 0 2 (4%)
      Proteinuria 0 0 1 (2%)
      Pulmonary embolism 1 (2%) 1 (2%) 2 (4%)
      Vomiting 0 2 (4%) 1 (2%)

      Conclusion
      This is the largest prospective trial of bevacizumab in poor PS pts with advanced NSCLC. All three regimens were safe and well-tolerated. ORRs with Pem/Bev +/- Cb were encouraging and comparable to historical outcomes in patients with better PS. PFS and OS data will be presented.