Adjei_subbed 27/11/08 10:33 Page 33
First-line Treatment of Metastatic Lung Cancer—New Developments
survival was found with the gemcitabine combination in 473 patients levels (cislatin/docetaxel for patients with low ERCC1 levels; docetaxel/
with squamous cell carcinoma (10.8 versus 9.4 months). gemcitabine for patients with high ERCC1 levels).
34
Response rates were
statistically higher in the genotypic arm. However, no differences were seen
Pemetrexed also took center stage in another placebo-controlled phase III in survival outcomes due to technical and design issues. This study
study that evaluated its role as maintenance treatment after first-line represents a pioneering effort in the establishment of ‘molecularly tailored’
chemotherapy compared with placebo. Median PFS showed statistically individualized therapy.
significant improvement (4.04 versus 1.97 months, HR 0.599; p<0.00001)
with a preliminary analysis showing a trend toward improvement in OS as Conclusions
well with the pemetrexed arm (13.01 versus 10.18 months, HR 0.798; While platinum-based doublets constitute the backbone of first-line
p=0.06). Similar to the results reported by Scagliotti et al., differential efficacy treatment for metastatic NSCLC, recent clinical findings with molecular
was demonstrated when results were stratified according to histology. therapies targeting various signaling pathways have bolstered enthusiasm in
Outcomes with pemetrexed were significantly improved among patients with this rapidly evolving field. The combination with bevacizumab in
non-squamous NSCLC, but not in patients with squamous histology.
31
appropriately selected patients is the standard in the first-line treatment of
patients with advanced NSCLC. Data are also emerging on the clinical utility
Such histological correlations are most likely a crude manifestation of the of combining cetuximab with front-line chemotherapy. In addition, the
underlying molecular heterogeity of NSCLC. Higher expression level of correlation between treatment efficacy and toxicity of novel molecular
thymidylate synthase, a pemetrexed target, in squamous histology has been targeted therapies and certain cytotoxic agents with histological subtypes of
demonstrated and is a plausible mechanism of relative resistance to NSCLC represents a simple approach toward therapy tailored to the
pemetrexed.
32
Similarly, data are emerging showing an direct correlation of molecular heterogeneity of NSCLC. Research is ongoing to validate markers
ERCC1 gene expression levels with platinum resistance.
33
A Spanish trial of tumor resistance or sensitivity specific to each drug, such as ERCC1 with
prospectively randomized over 400 patients to a control arm receiving cisplatin-based regimens. The use of maintenance chemotherapy in the
docetaxel plus cisplatin or an experimental genotype-based therapy arm front-line setting has found renewed potential with the availability of
wherein treatment was assigned based on ERCC1 messenger RNA [mRNA] effective and well-tolerated agents. ■
1. Chemotherapy in non-small cell lung cancer: a meta-analysis 12. IMCLONE Press Release, 2008. Available at: www.istockanalyst. 24. Camirand A, Lu Y, Pollak M, Co-targeting HER2/ErbB2 and
using updated data on individual patients from 52 randomized com/article/viewiStockNews+articleid_2562688.html insulin-like growth factor-1 receptors causes synergistic inhibition
clinical trials, Non-small Cell Lung Cancer Collaborative Group, 13. Johnson DH, Fehrenbacher L, Novotny WF, et al., Randomized of growth in HER2-overexpressing breast cancer cells, Med Sci
BMJ, 1995;311(7010):899–909. phase II trial comparing bevacizumab plus carboplatin and Monit, 2002;8:BR521–6.
2. Delbaldo C, Michiels S, Syz N, et al., Benefits of adding a drug to paclitaxel with carboplatin and paclitaxel alone in previously 25. Camirand A, Lu Y, Pollak M, Co-targeting HER2/ErbB2 and
a single-agent or a two-agent chemotherapy regimen in advanced untreated locally advanced or metastatic non-small-cell lung insulin-like growth factor-1 receptors causes synergistic inhibition
non-small cell lung cancer: a meta-analysis, JAMA, cancer, J Clin Oncol, 2004;22:2184–91. of growth in HER2-overexpressing breast cancer cells, Med Sci
2004;292(4):470–84. 14. Sandler A, Gray R, Perry MC, et al., Paclitaxel – carboplatin alone Monit, 2002;8:BR521–6.
3. Scagliotti GV, De Marinis F, Rinaldi M, et al., Phase III randomized or with bevacizumab for non-small-cell lung cancer, N Engl J Med, 26. Wiseman LR, Johnson MD, Wakeling AE, et al., Type I IGF receptor
trial comparing three platinum-based doublets in advanced 2006;355:2542–50. and acquired tamoxifen resistance in oestrogen-responsive human
non-small-cell lung cancer, J Clin Oncol, 2002;20:4285–4289. 15. Ramalingam SS, Dahlberg SE, Langer CJ, et al., Outcomes for breast cancer cells, Eur J Cancer, 1993;29A:2256–64.
4. Schiller JH, Harrington D, Belani CP, et al. Comparison of four elderly, advanced-stage non small-cell lung cancer patients treated 27. Gooch JL, Van Den Berg CL, Yee D, Insulin-like growth factor
chemotherapy regimens for advanced non-small-cell lung cancer, with bevacizumab in combination with carboplatin and paclitaxel: (IGF)-I rescues breast cancer cells from chemotherapy-induced cell
N Engl J Med, 2002;346:92–98. analysis of Eastern Cooperative Oncology Group Trial 4599, death – proliferative and anti-apoptotic effects, Breast Cancer Res
5. Cerny T, Barnes DM, Hasleton P, et al., Expression of epidermal J Clin Oncol, 2008;26(1):60–65. Treat, 1999;56(1):1–10.
growth factor receptor (EGF-R) in human lung tumours, Br J 16. Manegold C, von Pawel J, Zatloukal P, et al., Randomised, 28. Karp DD, Paz-Ares LG, Novello S, et al., High activity of the
Cancer, 1986;54(2):265–9. double-blind multicentre phase III study of bevacizumab in anti-IGF-1R antibody CP-751,871 in combination with paclitaxel
6. Giaccone G, Herbst RS, Manegold C, et al., Gefitinib in combination with cisplatin and gemcitabine in and carboplatin in squamous NSCLC, J Clin Oncol,
combination with gemcitabine and cisplatin in advanced chemotherapy-naïve patients with advanced or recurrent 2008;26:8015a.
non–small-cell lung cancer: A phase III trial – INTACT 1, non-squamous non-small cell lung cancer (NSCLC): BO17704, 29. Allerton JP, Hagenstad CT, Webb RT, et al., A phase II evaluation of
J Clin Oncol, 2004;22:777–84. Proc Am Soc Clin Oncol, 2007;25:LBA7514. the combination of paclitaxel protein-bound and carboplatin in
7. Herbst RS, Giaccone G, Schiller JH, et al., Gefitinib in combination 17. Genentech press release, 2008. Available at: www.gene.com/ the first-line treatment of advanced non-small cell lung cancer
with paclitaxel and carboplatin in advanced non-small-cell lung gene/news/press-releases/display.do?method=detail & id=11207 (NSCLC), Proc Am Soc Clin Oncol, 2006;24(18S):7127.
cancer: a phase III trial–INTACT 2, J Clin Oncol, 2004;22:785–94. 18. Bayer and Onyx press release, 2008. Available at: 30. Scagliotti GV, Parikh P, von Pawel J, et al., Phase III study
8. Herbst RS, Prager D, Hermann R, et al., TRIBUTE: a phase III trial www.medicalnewstoday.com/articles/105387.php comparing cisplatin plus gemcitabine with cisplatin plus
of erlotinib hydrochloride (OSI-774) combined with carboplatin 19. AstraZeneca press release, 2008. Available at: www.astrazeneca- pemetrexed in chemotherapy-naive patients with advanced-stage
and paclitaxel chemotherapy in advanced non-small-cell lung us.com/search/?itemId=2289031 non–small-cell lung cancer, J Clin Oncol, 26:3543–51.
cancer, J Clin Oncol, 2005;23:5892–9. 20. Heymach J, Paz-Ares L, De Braud F, et al., Randomized phase II 31. Ciuleanu TE, Brodowicz T, Belani CP, et al., Maintenance
9. Gatzemeier U, Pluzanska A, Szczesna A, et al., Results of a phase study of vandetanib (VAN) alone or in combination with pemetrexed plus best supportive care (BSC) versus placebo plus
III trial of erlotinib (OSI-774) combined with cisplatin and carboplatin and paclitaxel (CP) as first-line treatment for advanced BSC: A phase III study, J Clin Oncol, 2008;27(Suppl. 15):426s.
gemcitabine (GC) chemotherapy in advanced non-small cell lung non-small cell lung cancer (NSCLC), Proc Am Soc Clin Oncol, 32. Ceppi P, Volante M, Saviozzi S, et al., Squamous cell carcinoma of
cancer (NSCLC), J Clin Oncol, 2004;22:7010. 2007;25:7544. the lung compared with other isotopes shows higher messenger
10. Pirker R, Szczesna A, von Pawel J, et al., FLEX: A randomized, 21. Heymach JV, Johnson BE, Prager D, et al., Randomized, RNA and protein levels for thymidylate synthase, Cancer,
multicenter, phase III study of cetuximab in combination with placebo-controlled phase II study of vandetanib plus docetaxel in 2006;107:1589–96.
cisplatin/vinorelbine(CV) versus CV alone in the first-line treatment previously treated non-small cell lung cancer, J Clin Oncol, 33. Altaha R, Liang X, Yu JJ, et al., Excision repair
of patients with advanced non-small cell lung cancer (NSCLC), 2007;25(27):4270–77. cross-complementing-group 1: gene expression and platinum
J Clin Oncol, 2008;26: abstract 3. 22. Chang YS, Kong G, Sun S, et al., Clinical significance of insulin-like resistance, Int J Mol Med, 2004;14(6):959–70.
11. Lynch TJ, Patel T, Dreisbach L, et al., A randomized multicenter growth factor-binding protein-3 expression in stage I non-small 34. Cobo M, Isla D, Massuti B, et al., Customizing cisplatin based on
phase III study of cetuximab (Erbitux) in combination with cell lung cancer, Clin Cancer Res, 2002;8:3796–3802. quantitative excision repair cross-complementing 1 mRNA
Taxane/Carboplatin versus Taxane/carboplatin alone as first line 23. Allen GW, Saba C, Armstrong EA, et al., Insulin-like growth factor-I expression: A phase III trial in non–small-cell lung cancer, J Clin
treatment for patients with advanced /metastatic non-small cell receptor signaling blockade combined with radiation, Cancer Res, Oncol, 2007;25:2747–54.
lung cancer, J Thoracic Oncol, 2007;2(Suppl. 4):B3–30. 2007;67:1155–62.
US ONCOLOGY 33
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84