Combination of Angiogenesis Inhibitor (Endostar) and EGFR-TKIs in Patients with
PUBLISHED: 2015-11-26  283 total views, 1 today

Ruifen Tian1, Yi Guo2, Rong Wang2, Xia Zhang2Wei Guo2, Haibo Zhu2

1Pulmonary Oncology,Shanxi Cancer Hospital, Shanxi Medical University Cancer Hospital, 2Department of PulmonaryOncfology, Shanxi Cancer Hospital


Objective:To evaluate the clinical activity ofangiogenesis inhibitor Endostar (rh-endostatin) in combination with continued EGFR-TKIs(including erlotinib, gefitinib and IcotinibO) for advanced NSCLC patients whohave developed acquired resistance to prior EGFR-TKIs treatment. Method: AdvancedNSCLC patients with disease progression who had partial or complete response toprior EGFR-TKIs treatment received 2-8 cycles of Endostar plus EGFR-TKIs.Endostar was administered at a dose of 15mg q.d intravenously for 14 days, eachat 3-week intervals; combined with continued EGFR-TKIs (erlotinib 150mg POdaily, or gefitinib 250mg PO daily or Icotinib 125mg PO t.i.d); untilunacceptable toxicity or disease progression. The response was assessed usingSouthwest Oncology Group (SWOG) criteria after 6 weeks. Result: A totalof 17 NSCLC evaluable patients were enrolled, including 9 women and 8 men. Thepresence of EGFR status were exon 21 L858R point mutation in 7 cases, exon 19deletion in 5 cases, wild type in 2 cases and unknown in 3 cases. Median numberof treatment cycles was four. It showed a 76.47% (13/17) disease control rateand had a prolonged stabilization of disease (>6months). Median PFS was 6.9Months. Treatment benefit and overall survival was noted both in activatingEGFR mutation patients, EGFR stated unknown patients and even in wild typepatients. One stage VI patient with EGFR wild type, developed resistance after6 months 2nd line erlotinib treatment, received 8 cycles of Endstarand erlotinib combination, and had 46 months overall survival time. Endostar incombination with EGFR-TKIs were generally well tolerated.  The most commonadverse events were rash 35.29% (6/17), decreased appetite 29.41% (5/17), dryskin 29.41% (5/17). No grade 3 or greater adverse events were seen in thisstudy. Conclusion: Endostar with the addition of continuation ofEGFR-TKIs has demonstrated promising clinical activity in NSCLC patientsselected for acquired resistance to previous use of EGFR-TKIs. Treatment withthis combination exhibited a good safety profile. Our results strengthen theevidence that angiogenesis inhibitor may be a valid option for NSCLC patientswho have progressed on EGFR-TKIs. The optimal clinical combination and activitywarrants further investigation.


Key Words: Endostar  EGFR-TKIs Non-small cell lung cancer

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