Yonsei Med J.  2010 Jan;51(1):1-8. 10.3349/ymj.2010.51.1.1.

The Role of Monoclonal Antibody in Combination with First-Line Chemotherapy in Asian Patients with Advanced Non-Small Cell Lung Cancer

• Cho BC
• Kim JH
• Soo RA
• Yang CH

• KMID: 1779599
• DOI: http://doi.org/10.3349/ymj.2010.51.1.1

Abstract

The strategies of incorporating monoclonal antibodies (MoABs) have now proved efficacy in the first-line treatment of advanced non-small cell lung cancer (NSCLC). These include targeting the vascular endothelial growth factor (VEGF) or epidermal growth factor receptor (EGFR). Bevacizumab is a MoAB targeting the vascular endothelial growth factor (VEGF), an important mediator of new blood vessel formation. Cetuximab is a MoAB directed at EGFR. Binding cetuximab to EGFR blocks signal transduction and promotes receptor internalization and degradation. In this review, we present current data of bevacizumab and cetuximab for the first line treatment of advanced NSCLC. We also refer to their potential for Asian patients with advanced NSCLC in the first-line setting.

Keyword

Non-small cell lung cancer; chemotherapy; monoclonal antibody; bevacizumab; cetuximab

MeSH Terms

Antibodies, Monoclonal/*therapeutic use
Antineoplastic Agents/*therapeutic use
Asian Continental Ancestry Group
Carcinoma, Non-Small-Cell Lung/*drug therapy
Humans

Reference

1. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, et al. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004. 22:2184–2191.

2. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006. 355:2542–2550.

3. Reck M, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009. 27:1227–1234.

4. Jänne PA, Engelman JA, Johnson BE. Epidermal growth factor receptor mutations in non-small cell lung cancer: implications for treatment and tumor biology. J Clin Oncol. 2005. 23:3227–3234.

5. Dowlati A, Gray R, Sandler AB, Schiller JH, Johnson DH. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab--an Eastern Cooperative Oncology Group Study. Clin Cancer Res. 2008. 14:1407–1412.

6. Manegold C, von Pawel J, Zatloukal P, Ramlau R, Gorbounova V, Hirsh V, et al. BO17704 (AVAiL): a phase III randomised study of first-line bevacizumab combined with cisplatin/gemcitabine in patients with advanced or recurrent non-squamous, non-small cell lung cancer (NSCLC). Ann Oncol. 2008. 19:9S. (abstr LBA1).

7. Pirker R, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Park K, et al. FLEX: a randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2008. 26:(May 20 Suppl; abstr 3).

8. Sandler AB, Schiller JH, Gray R, Dimery I, Brahmer J, Samant M, et al. Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with carboplatin and paclitaxel plus bevacizumab. J Clin Oncol. 2009. 27:1405–1412.

9. Gordon MS, Margolin K, Talpaz M, Sledge GW Jr, Holmgren E, Benjamin R, et al. Phase I safety and pharmacokinetic study of recombinant human anti-vascular endothelial growth factor in patients with advanced cancer. J Clin Oncol. 2001. 19:843–850.

10. Akerley WL, Langer CJ, Oh Y, Strickland DK, Joo Royer S, Xia Q, et al. Acceptable safety of bevacizumab therapy in patients with brain metastases due to non-small cell lung cancer. J Clin Oncol. 2008. 26:(May 20 Suppl; abstr 8043).

11. Archer V, Reck M, Sandler AB, Johnson DH, Kong G, Strickland DK, et al. Risk of symptomatic central nervous system (CNS) progression and secondary hemorrhage in patients with non-squamous non-small cell lung cancer (NSCLC) receiving bevacizumab (BV)-based first-line therapy. J Clin Oncol. 2008. 26:(May 20 Suppl; abstr 8114).

12. Dansin E, Mezger J, Isla D, Barlesi F, Bearz A, Garrido Lopez P, et al. Safety of bevacizumab-based therapy as first-line treatment of patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): MO19390 (SAiL). J Clin Oncol. 2008. 26:(May 20 Suppl; abstr 8085).

13. Griesinger F, Laskin JJ, Pavlakis N. on behalf of the MO19390 (SAiL) study group. Safety of first-line bevacizumab-based therapy with concomitant cardiovascular or anticoagulation medication in advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in MO19390 (SAiL). J Clin Oncol. 2008. 26:(May 20 Suppl; abstr 8049).

14. Vosseler S, Mirancea N, Bohlen P, Mueller MM, Fusenig NE. Angiogenesis inhibition by vascular endothelial growth factor receptor-2 blockade reduces stromal matrix metalloproteinase expression, normalizes stromal tissue, and reverts epithelial tumor phenotype in surface heterotransplants. Cancer Res. 2005. 65:1294–1305.

15. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004. 350:2335–2342.

16. Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, et al. Outcomes for elderly, advanced-stage non-small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008. 26:60–65.

17. Nishio M, Horai T, Kunitoh H, Ichinose Y, Nishiwaki Y, Hida T, et al. Randomized, open-label, multicenter phase II sutdy of bevacizumab in combination with carboplatin and paclitaxel in chemotherapy-naive Japanese patients with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC): JO19907. J Clin Oncol. 2009. 27:(Suppl; abstr 8036).

18. Dowlati A, Gray R, Sandler AB, Schiller JH, Johnson DH. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab--an Eastern Cooperative Oncology Group Study. Clin Cancer Res. 2008. 14:1407–1412.

19. Leighl N, Reck M, de Haas S, Evers S, Delmar P, Manegold C, et al. Analysis of biomarkers in the AVAiL phase III randomised study of first-line bevacizumab with cisplatin-gemcitabine in patients with non-small cell lung cancer. Eur J Cancer. 2009. 7:(abstr 9172).

20. Rosell R, Robinet G, Szczesna A, Ramlau R, Constenla M, Mennecier BC, et al. Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer. Ann Oncol. 2008. 19:362–369.

21. Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, et al. Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol. 2007. 25:5777–5784.

22. Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim W, Hermann RC, et al. Overall survival results from the phase III trial BMS 099: Cetuximab + taxane/carboplatin as 1st-line treatment for advanced NSCLC. J Thorac Oncol. 2008. 3:Suppl 4. S305.

23. Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer(FLEX): an open-label randomised phase III trial. Lancet. 2009. 373:1525–1531.

24. Nick T, Lynch TJ, Butts C, Rosell R, Shepherd F, Jean-Louis P, et al. Cetuximab plus platinum-based chemotherapy as 1st-line treatment in patients with non-small cell lung cancer (NSCLC): a meta-analysis of randomized phase II/III trials. J Thorac Oncol. 2009. 4:Suppl 1. S297.

25. Pirker R, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Park K, et al. FLEX: a randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2008. 26:(May 20 Suppl; abstr 3).

26. Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, et al. Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol. 2005. 23:1803–1810.

27. Cappuzzo F, Finocchiaro G, Rossi E, Jänne PA, Carnaghi C, Calandri C, et al. EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients. Ann Oncol. 2008. 19:717–723.

28. Hirsch FR, Herbst RS, Olsen C, Chansky K, Crowley J, Kelly K, et al. Increased EGFR gene copy number detected by fluorescent In situ hybridization predicts outcome in non-small-cell lung cancer patients treated with cetuximab and chemotherapy. J Clin Oncol. 2008. 26:3351–3357.

29. Khambata-Ford S, Garrett CR, Meropol NJ, Basik M, Harbison CT, Wu S, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007. 25:3230–3237.

30. Frattini M, Saletti P, Romagnani E, Martin V, Molinari F, Ghisletta M, et al. PTEN loss of expression predicts cetuximab efficacy in metastatic colorectal cancer patients. Br J Cancer. 2007. 97:1139–1145.

31. Peréz-Soler R, Saltz L. Cutaneous adverse effects with HER1/EGFR-targeted agents: is there a silver lining? J Clin Oncol. 2005. 23:5235–5246.

32. Gatzemeier U, Paz-Ares L, Rodrigues Pereira J, von Pawel J, Ramlau R, Roh JK, et al. Molecular and clinical biomarkers of cetuximab efficacy: data from the phase III FLEX study in non-small cell lung cancer (NSCLC). J Thorac Oncol. 2009. 4:Suppl 1. S324.