Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers Journal Article

Authors: Chaft, J. E.; Rusch, V.; Ginsberg, M. S.; Paik, P. K.; Finley, D. J.; Kris, M. G.; Price, K. A. R.; Azzoli, C. G.; Fury, M. G.; Riely, G. J.; Krug, L. M.; Downey, R. J.; Bains, M. S.; Sima, C. S.; Rizk, N.; Travis, W. D.; Rizvi, N. A.
Article Title: Phase II trial of neoadjuvant bevacizumab plus chemotherapy and adjuvant bevacizumab in patients with resectable nonsquamous non-small-cell lung cancers
Abstract: INTRODUCTION: Bevacizumab improves survival in patients with advanced non-small-cell lung cancer (NSCLC). This phase II clinical trial assessed the effects of the addition of bevacizumab to neoadjuvant chemotherapy in resectable nonsquamous NSCLC. METHODS: Patients with resectable stage IB-IIIA nonsquamous NSCLC were treated with bevacizumab followed by imaging 2 weeks later to assess single-agent effect. After this they received two cycles of bevacizumab with four cycles of cisplatin and docetaxel followed by surgical resection. Resected patients were eligible for adjuvant bevacizumab. The primary endpoint was the rate of pathological downstaging (decrease from pretreatment clinical stage to post-treatment pathological stage). Secondary endpoints included overall survival, safety, and radiologic response. RESULTS: Fifty patients were enrolled. Thirty-four (68%) were clinical stage IIIA. All three doses of neoadjuvant bevacizumab were delivered to 40 of 50 patients. Six patients (12%) discontinued because of bevacizumab-related adverse events. The rate of downstaging (38%), response to chemotherapy (45%), and perioperative complications (12%) were comparable with historical data. No partial responses were observed to single-agent bevacizumab, but 18% of the patients developed new intratumoral cavitation, with a trend toward improved pathologic response (57% versus 21%; p = 0.07). A major pathologic response (≥90% treatment effect) was associated with survival at 3 years (100% versus 49%; p = 0.01). No patients with KRAS-mutant NSCLC (0 of 10) had a pathologic response as compared with 11 of 31 with wild-type KRAS. CONCLUSION: Although preoperative bevacizumab plus chemotherapy was feasible, it did not improve downstaging in unselected patients. New cavitation after single-agent bevacizumab is a potential biomarker. Alternative strategies are needed for KRAS-mutant tumors. © 2013 by the International Association for the Study of Lung Cancer.
Keywords: adult; cancer survival; clinical article; human tissue; treatment response; aged; cancer surgery; gene mutation; overall survival; bevacizumab; cisplatin; advanced cancer; drug safety; drug withdrawal; monotherapy; cancer adjuvant therapy; cancer patient; cancer staging; multiple cycle treatment; phase 2 clinical trial; lung non small cell cancer; drug effect; wild type; docetaxel; adjuvant chemotherapy; surgery; neoadjuvant chemotherapy; recombinant granulocyte colony stimulating factor; k ras protein; premedication; peroperative complication; lung cavitation; pathologic response; non?small-cell lung cancer
Journal Title: Journal of Thoracic Oncology
Volume: 8
Issue: 8
ISSN: 1556-0864
Publisher: Elsevier Inc.  
Date Published: 2013-08-01
Start Page: 1084
End Page: 1090
Language: English
DOI: 10.1097/JTO.0b013e31829923ec
PROVIDER: scopus
PUBMED: 23857398
PMCID: PMC4191830
Notes: --- - Cited By (since 1996):1 - "Export Date: 4 September 2013" - "Source: Scopus"
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MSK Authors
  1. Camelia S Sima
    204 Sima
  2. Valerie W Rusch
    655 Rusch
  3. Michelle S Ginsberg
    158 Ginsberg
  4. Lee M Krug
    211 Krug
  5. Nabil Rizk
    134 Rizk
  6. Christopher G Azzoli
    105 Azzoli
  7. Katharine A R Price
    10 Price
  8. Naiyer A Rizvi
    157 Rizvi
  9. David John Finley
    39 Finley
  10. Jamie Erin Chaft
    127 Chaft
  11. Matthew G Fury
    93 Fury
  12. William D Travis
    548 Travis
  13. Gregory J Riely
    346 Riely
  14. Paul K Paik
    88 Paik
  15. Robert J Downey
    203 Downey
  16. Manjit S Bains
    229 Bains
  17. Mark Kris
    603 Kris