Anti-Angiogenesis Antibody: Bevacizumab

Neha Vapiwala, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 27, 2005

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Review of Pivotal Bevacizumab Studies – Colorectal Cancer

  • Phase I clinical trials (Gordon et al., Margolin et al.) established a half-life of 21 days, lack of dose-limiting toxicity, and safety/tolerability when bevacizumab is given with chemotherapy.
  • Phase II clinical trial (Kabbinavar et al.) established an overall response rate (RR) of 32% with the addition of bevacizumab to standard chemotherapy (5-FU/Leucovorin) in previously untreated metastatic colorectal cancer (CRC) patients, compared to a 17% RR with chemotherapy alone. Specifically, the "low-dose" bevacizumab arm (5 mg/kg) demonstrated a 40% RR, compared to 24% with the "high-dose" arm (10 mg/kg). Median time-to-disease-progression (TTP, 9 vs. 5.2 months, p=0.005) and median progression-free survival (PFS, 9.2 vs. 5.5 mos, p=0.0002) were also statistically significantly better with the combination of low-dose bevacizumab and chemotherapy vs. chemotherapy alone.
  • Phase III clinical trial (Hurwitz et al.) established a statistically significant median overall survival (OS) benefit with low-dose bevacizumab and IFL (Irinotecan, 5-FU, Leucovorin) chemotherapy, compared to placebo and IFL chemotherapy (20.3 vs. 15.6 mos, p<0.001), in previously untreated CRC patients.

Review of Additional Bevacizumab Studies – Colorectal Cancer

  • Second-line therapy in previously treated metastatic CRC patients: The E3200 trial (Giantonio et al.) looked at high-dose bevacizumab in combination with FOLFOX-4 chemotherapy a combination of oxaliplatin, fluorouracil (5-FU), and leucovorin), compared to either treatment alone. RR (21.8% vs. 9.2%, p<0.0001), PFS (7.2 vs. 4.8 mos, p<0.0001), and OS (12.9 vs. 10.8 mos, p=0.0018) were all statistically significantly better with the combination compared to FOLFOX-4 alone.
  • Refractory disease in heavily treated metastatic CRC patients: RR of 1-4%, TTP of 3-4 months.
  • Irinotecan-refractory disease in metastatic CRC patients: The BOND trials found greater RR and TTP with the combination of irinotecan, bevacizumab, and cetuximab in patients no longer responding to irinotecan-based chemotherapy.
  • Trials underway:
    • CALGB/SWOG Phase III study of patients with metastatic CRC treated with FOLFOX or FOLFIRI chemotherapy, then randomized to either cetuximab, bevacizumab, or both.
    • NSABP C-08 Phase III study of stage II/III CRC patients after surgical resection treated with adjuvant FOLFOX with or without bevacizumab.

Review of Bevacizumab Studies – Gastric/ Gastroesophageal Junction Cancer

  • Phase I/II trial (Shah et al.) of 23 metastatic gastric and gastroesophageal cancer patients treated with irinotecan/cisplatin chemotherapy + bevacizumab 15 mg/kg found RR of 61%, with 95% of patients free of disease progression at 3 months.
  • MAGIC 2 trial (Cunningham et al.) underway in UK: preoperative chemotherapy x 3 cycles à surgery à postoperative chemotherapy x 3 cycles. Patients then randomized to bevacizumab or placebo. Chemotherapy regimen is ECX: epirubicin, cisplatin, capecitabine. RESULTS PENDING
  • Trials underway:
    • second-line therapy for GE junction cancer with bevacizumab and docetaxel (Dana Farber Cancer Institute)
    • first-line therapy for GE junction cancer with bevacizumab and preoperative irinotecan/cisplatin/radiation therapy (Dana Farber Cancer Institute)
    • first-line therapy for esophageal cancer with bevacizumab and preoperative irinotecan/cisplatin/radiation therapy (Memorial Sloan-Kettering Cancer)

Review of Bevacizumab Studies – Pancreatic Cancer

  • Phase II trial (Kindler et al.) of bevacizumab and gemcitabine chemotherapy showed RR of 19%, median OS of 8.7 mos, and 6-month survival rate of 75%
  • Trials underway:
    • CALGB: Phase III – gemcitabine with or without bevacizumab
    • RTOG: Unresectable disease – capecitabine + radiation therapy à bevacizumab à gemcitabine + bevacizumab
    • ECOG: Unresectable disease – gemcitabine + radiation therapy with either bevacizumab or cetuximab

Review of Bevacizumab Studies –Hepatocellular Cancer

  • Phase II study (Zhu et al.) of bevacizumab with gemcitabine and oxaliplatin produced 2 partial responses out of 27 patients treated.

Review of Bevacizumab Studies – Breast Cancer

  • Phase III study of 646 patients with metastatic breast cancer found prolonged PFS using first-line treatment regimen of bevacizumab (10 mg/kg) and paclitaxel: PFS of 10.7 months compared to 6.1 months with paclitaxel alone. (Clin Breast Cancer 2005 Jun;6:105-107)

Review of Bevacizumab Studies – Non-Small Cell Lung Cancer

  • Preliminary results of ECOG 4599 phase III study of over 700 patients with advanced non-small-cell lung cancer show prolonged OS using first-line treatment regimen of bevacizumab (15 mg/kg), paclitaxel, and carboplatin: OS of 12.5 months vs. 10.2 months with chemotherapy doublet alone (Clin Lung Cancer 2005 Mar;6(5):276-8)


News
Bevacizumab increases risk of fatal adverse events for patients on other cancer therapies

Feb 2, 2011 - The number of fatal adverse events in cancer patients treated with the angiogenesis inhibitor bevacizumab in combination with chemotherapy or biological therapy is higher than those treated with chemotherapy alone, according to a review published in the Feb. 2 issue of the Journal of the American Medical Association.



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