A Phase II Study of Erlotinib in Patients with Previously Treated Non-Small Cell Lung Cancer

Abstract Full-Text HTML Download Download as PDF (Size:924KB) PP. 10-20
DOI: 10.4236/alc.2014.31002    3,927 Downloads   6,708 Views   Citations

ABSTRACT

Background: Erlotinib has been reported to be effective for the treatment of non-small cell lung cancer (NSCLC). To evaluate the efficacy and safety of erlotinib under conditions similar to daily clinical practice, a phase II trial was conducted in Japanese patients with previously treated NSCLC. Methods: The eligibility criteria were stage IIIB/IV NSCLC, a performance status (PS) of 0 - 2, and previous treatment with 1 - 2 non-EGFR-TKI regimens. Patients received erlotinib (150 mg/day) orally until disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR). In addition, the disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and EGFR gene mutation status were evaluated. Results: Thirty-eight patients were enrolled, and 37 patients were evaluated. The median age was 69 years (range, 50 - 80 years). Patient characteristics were as follows: 26 were male and 11 were female; 12 had a PS of 0, 20 had a PS of 1, and 5 had a PS of 2; and 26 had adenocarcinoma, and 11 had non-adenocarcinoma histology. The ORR and DCR were 21.6% (95% confidence interval [CI], 11.4% - 37.2%) and 54.1% (95% CI, 35.9% - 66.6%), respectively. Twenty-seven patients could be evaluated for EGFR gene status (12, mutated; 15, wild-type). The ORR for EGFR-mutated patients was 41.7%, while that for patients with wild-type EGFR was 13.3%. The median PFS was evaluated as 4.4 months (95% CI, 2.2 - 10.7 months). The median OS was 14.9 months (95% CI, 9.2 months - not reached). Common adverse events were tolerable skin toxicities, diarrhea, and stomatitis. In addition, interstitial lung disease occurred in 8.1% of patients. Conclusion: As efficacy and safety were similar to previous studies, erlotinib was found to be effective for Japanese patients with previously treated NSCLC in clinical practice.

Cite this paper

Kubota, T. , Okano, Y. , Sakai, M. , Yamane, T. , Shiota, N. , Ohnishi, H. , Machida, H. , Hatakeyama, N. , Takeuchi, E. , Urata, T. , Ogushi, F. and Yokoyama, A. (2014) A Phase II Study of Erlotinib in Patients with Previously Treated Non-Small Cell Lung Cancer. Advances in Lung Cancer, 3, 10-20. doi: 10.4236/alc.2014.31002.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Matsuda, T., Marugane, T., Kamo, K., Katanoda, K., Ajiki, W., Sobue, T. and Japan Cancer Surveilance Research Group (2012) Cancer Incidence and Incidence Rates in Japan in 2006: Based on Data from 15 Population-Based Cancer Registries in the Monitoring of Cancer Incidence in Japan (MCIJ) Project. Japanese Journal of Clinical Oncology, 42, 139-147. http://dx.doi.org/10.1093/jjco/hyr184
[2] Siegel, R., Naishadham, D. and Jemal, A. (2013) Cancer Statistics, 2013. CA: A Cancer Journal for Clinitians, 63, 11-30. http://dx.doi.org/10.3322/caac.21166
[3] Herbst, R.S., Heymach, J.V. and Lippman, S.M. (2008) Lung Cancer. New England Journal of Medicine, 359, 1367-1380. http://dx.doi.org/10.1056/NEJMra0802714
[4] Schiller, J.H., Harrington, D., Belani, C.P., Langer, C., Sandler, A., Krook, J., Zhu, J., Johnson, D.H. and Eastern Cooperative Oncology Group (2002) Comparison of Four Chemotherapy Regimens for Advanced Non-Small-Cell Lung Cancer. New England Journal of Medicine, 346, 92-98.
http://dx.doi.org/10.1056/NEJMoa011954
[5] Ciardiello, F. and Tortora, G. (2008) EGFR Antagonists in Cancer Treatment. New England Journal of Medicine, 358, 1160-1174. http://dx.doi.org/10.1056/NEJMra0707704
[6] Shepherd, F.A., Rodrigues Pereira, J.R., Ciuleanu, T., Tan, E.H., Hirsh, V., Thongprasert, S., Campos, D., Maoleekoonpiroj, S., Smylie, M., Martins, R., Van Kooten, M., Dediu, M., Findlay, B., Tu, D., Johnston, D., Bezjak, A., Clark, G., Santabárbara, P., Seymour, L. and National Cancer Institute of Canada Clinical Trials Group (2005) Erlotinib in Previously Treated Non-Small-Cell Lung Cancer. New England Journal of Medicine, 353, 123-132. http://dx.doi.org/10.1056/NEJMoa050753
[7] Johnson, J.R., Cohen, M., Sridhara, R., Chen, Y.F., Williams, G.M., Duan, J., Gobburu, J., Booth, B., Benson, K., Leighton, J., Hsieh, L.S., Chidambaram, N., Zimmerman, P. and Pazdur, R. (2005) Approval Summary for Erlotinib for Treatment of Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer after Failure of at Least One Prior Chemotherapy Regimen. Clinical Cancer Research, 11, 6414-6421. http://dx.doi.org/10.1158/1078-0432.CCR-05-0790
[8] Cataldo, V.D., Gibbons, D.L., Pérez-Soler, R. and Quintás-Cardama, A. (2011) Treatment of Non-Small-Cell Lung Cancer with Erlotinib or Gefitinib. New England Journal of Medicine, 364, 947-955. http://dx.doi.org/10.1056/NEJMct0807960
[9] Maemondo, M., Inoue, A., Kobayashi, K., Sugawara, S., Oizumi, S., Isobe, H., Gemma, A., Harada, M., Yoshizawa, H., Kinoshita, I., Fujita, Y., Okinaga, S., Hirano, H., Yoshimori, K., Harada, T., Ogura, T., Ando, M., Miyazawa, H., Tanaka, T., Saijo, Y., Hagiwara, K., Morita, S., Nukiwa, T. and North-East Japan Study Group (2010) Gefitinib or Chemotherapy for Non-Small-Cell Lung Cancer with Mutated EGFR. New England Journal of Medicine, 362, 2380-2388. http://dx.doi.org/10.1056/NEJMoa0909530
[10] Mok, T.S., Wu, Y.L., Thongprasert, S., Yang, C.H., Chu, D.T., Saijo, N., Sunpaweravong, P., Han, B., Margono, B., Ichinose, Y., Nishiwaki, Y., Ohe, Y., Yang, J.J., Chewaskulyong, B., Jiang, H., Duffield, E.L., Watkins, C.L., Armour, A.A. and Fukuoka, M. (2009) Gefitinib or Carboplatin-Paclitaxel in Pulmonary Adenocarcinoma. New England Journal of Medicine, 361, 947-957. http://dx.doi.org/10.1056/ NEJMoa0810699
[11] Mitsudomi, T., Morita, S., Yatabe, Y., Negoro, S., Okamoto, I., Tsurutani, J., Seto, T., Satouchi, M., Tada, H., Hirashima, T., Asami, K., Katakami, N., Takada, M., Yoshioka, H., Shibata, K., Kudoh, S., Shimizu, E., Saito, H., Toyooka, S., Nakagawa, K., Fukuoka, M. and West Japan Oncology Group (2010) Gefitinib versus Cisplatin plus Docetaxel in Patients with Non-Small-Cell Lung Cancer Harbouring Mutations of the Epidermal Growth Factor Receptor (WJTOG3405): An Open Label, Randomized Phase 3 Trial. Lancet Oncology, 11, 121-128. http://dx.doi.org/10.1016/S1470-2045 (09)70364-X
[12] Yoshioka, H., Hotta, K., Kiura, K., Takigawa, N., Hayashi, H., Harita, S., Kuyama, S., Segawa, Y., Kamei, H., Umemura, S., Bessho, A., Tabata, M., Tanimoto, M. and Okayama Lung Cancer Study Group (2010) A Phase II Trial of Erlotinib Monotherapy in Pretreated Patients with Advanced Non-Small Cell Lung Cancer Who Do Not Possess Active EGFR Mutations. Journal of Thoracic Oncology, 5, 99-104. http://dx.doi.org/10.1097/JTO.0b013e3181c20063
[13] Kobayashi, T., Koizumi, T., Agatsuma, T., Yasuo, M., Tsushima, K., Kubo, K., Eda, S., Kuraishi, H., Koyama, S., Hachiya, T. and Ohura, N. (2012) A Phase II Trial of Erlotinib in Patients with EGFR Wild-Type Advanced NonSmall-Cell Lung Cancer. Cancer Chemotherapy and Pharmacology, 69, 1241-1246. http://dx.doi.org/10.1007/s00280-012-1831-0
[14] Kubota, K., Nishiwaki, Y., Tamura, T., Nakagawa, K., Matsui, K., Watanabe, K., Hida, T., Kawahara, M., Katakami, N., Takeda, K., Yokoyama, A., Noda, K., Fukuoka, M. and Saijo, N. (2008) Efficacy and Safety of Erlotinib Monotherapy for Japanese Patients with Advanced Non-Small Cell Lung Cancer. A phase II Study. Journal of Thoracic Oncology, 3, 1439-1445. http://dx.doi.org/10.1097/JTO. 0b013e31818d6702
[15] Takahashi, T., Yamamoto, N., Nukiwa, T., Mori, K., Tsuboi, M., Horai, T., Masuda, N., Eguchi, K., Mitsudomi, T., Yokota, S., Segawa, Y., Ichinose, Y., Fukuoka, M. and Saijo, N. (2010) Phase II Study of Erlotinib in Japanese Patients with Advanced Non-Small Cell Lung Cancer. Anticancer Research, 30, 557-563.
[16] Yamada, K., Takayama, K., Kawakami, S., Saruwatari, K., Morinaga, R., Harada, T., Aragane, N., Nagata, S., Kishimoto, J., Nakanishi, Y. and Ichinose, Y. (2013) Phase II Trial of Erlotinib for Japanese Patients with Previously Treated Non-Small-Cell Lung Cancer Harboring EGFR Mutations: Results of Lung Oncology Group in Kyusyu (LOGiK0803). Japanese Journal of Clinical Oncology, 43, 629-635. http://dx.doi.org/10.1093/jjco/hyt056
[17] Yoshida, K., Yatabe, Y., Park, J.Y., Shimizu, J., Horio, Y., Matsuo, K., Kosaka, T., Mitsudomi, T. and Hida, T. (2007) Prospective Validation for Prediction of Gefitinib Sensitivity by Epidermal Growth Factor Receptor Gene Mutation in Patients with Non-Small Cell Lung Cancer. Journal of Thoracic Oncology, 2, 22-28. http://dx.doi.org/10.1097/01243894-200701000-00006
[18] Nagai, Y., Miyazawa, H., Huqun, Tanaka, T., Udagawa, K., Kato, M., Fukuyama, S., Yokote, A., Kobayashi, K., Kanazawa, M. and Hagiwara, K. (2005) Genetic Heterogeneity of the Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer Cell Lines Revealed by a Rapid and Sensitive Detection System, the Peptide Nucleic Acid-Locked Nucleic Acid PCR Clamp. Cancer Research, 65, 7276-7282. http://dx.doi.org/10.1158/0008-5472.CAN-05-0331
[19] Lynch, T.J., Bell, D.W., Sordella, R., Gurubhagavatula, S., Okimoto, R.A., Brannigan, B.W., Harris, P.L., Haserlat, S.M., Supko, J.G., Haluska, F.G., Louis, D.N., Christiani, D.C., Settleman, J. and Haber, D.A. (2004) Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib. New England Journal of Medicine, 350, 2129-2139. http://dx.doi.org/10.1056/NEJMoa040938
[20] Engleman, J.A. and Janne, P.A. (2005) Factors Predicting Response to EGFR Tyrosine Kinase Inhibitors. Seminars in Respiratory and Critical Care Medicine, 26, 314-322.
http://dx.doi.org/10.1055/s-2005-871990
[21] Zhou, C., Wu, Y.L., Chen, G., Feng, J., Liu, X.Q., Wang, C., Zhang, S., Wang, J., Zhou, S., Ren, S., Lu, S., Zhang, L., Hu, C., Hu, C., Luo, Y., Chen, L., Ye, M., Huang, J., Zhi, X., Zhang, Y., Xiu, Q., Ma, J., Zhang, L. and You, C. (2011) Erlotinib versus Chemotherapy as First-Line Treatment for Patients with Advanced EGFR Mutation-Positive NonSmall-Cell Lung Cancer (OPTIMAL, CTONG-0802): A Multicenter, Open-Label, Randomized, Phase 3 Study. Lancet Oncology, 12, 735-742. http://dx.doi.org/10.1016/ S1470-2045(11)70184-X
[22] Rosell, R., Carcereny, E., Gervais, R., Vergnenegre, A., Massuti, B., Felip, E., Palmero, R., Garcia-Gomez, R., Pallares, C., Sanchez, J.M., Porta, R., Cobo, M., Garrido, P., Longo, F., Moran, T., Insa, A., De Marinis, F., Corre, R., Bover, I., Illiano, A., Dansin, E., De Castro, J., Milella, M., Reguart, N., Altavilla, G., Jimenez, U., Provencio, M., Moreno, M.A., Terrasa, J., Munoz-Langa, J., Valdivia, J., Isla, D., Domine, M., Molinier, O., Mazieres, J., Baize, N., Garcia-Campelo, R., Robinet, G., Rodriguez-Abreu, D., Lopez-Vivanco, G., Gebbia, V., Ferrera-Delgado, L., Bombaron, P., Bernabe, R., Bearz, A., Artal, A., Cortesi, E., Rolfo, C., Sanchez-Ronco, M., Drozdowskyj, A., Queralt, C., De Aguirre, I., Ramirez, J.L., Sanchez, J.J., Molina, M.A., Taron, M., Paz-Ares, L. and Spanish Lung Cancer Group in Collaboration with Groupe Francais de Pneumo-Cancérologie and Associazione Italian Oncologia Toracica (2012) Erlotinib versus Standard Chemotherapy as First-Line Treatment for European Patients with Advanced EGFR Mutation-Positive NonSmall-Cell Lung Cancer (EURTAC): A Multicenter, Open-Label, Randomized Phase 3 Trial. Lancet Oncology, 13, 239-246. http://dx.doi.org/10.1016/S1470-2045 (11)70393-X
[23] Smith, J. (2005) Erlotinib: Small-Molecule Targeted Therapy in the Treatment of Non-Small-Cell Lung Cancer. Clinical Therapeutics, 27, 1513-1534. http://dx.doi.org/10.1016/j.clinthera.2005.10.014
[24] Lee, S.M., Khan, I., Upadhyay, S., Lewanski, C., Falk, S., Skailes, G., Marshall, E., Woll, P.J., Hatton, M., Lal, R., Jones, R., Toy, E., Chao, D., Middleton, G., Bulley, S., Ngai, Y., Rudd, R., Hackshaw, A. and Boshoff, C. (2012) First-Line Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer Unsuitable for Chemotherapy (TOPICAL): A Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet Oncology, 13, 1161-1170. http://dx.doi.org/10.1016/S1470-2045(12)70412-6
[25] Garassino, M.C., Martelli, O., Broggini, M., Farina, G., Veronese, S., Rulli, E., Bianchi, F., Bettini, A., Longo, F., Moscetti, L., Tomirotti, M., Marabese, M., Ganzinelli, M., Lauricella, C., Labianca, R., Floriani, I., Giaccone, G., Torri, V., Scanni, A., Marsoni, S. and TAILOR Trialists (2013) Erlotinib versus Docetaxel as Second-Line Treatment of Patients with Advanced Non-Small-Cell Lung Cancer and Wild-Type EGFR Tumors (TAILOR): A Randomized Control Trial. Lancet Oncology, 14, 981-988.
http://dx.doi.org/10.1016/S1470-2045(13)70310-3
[26] Pérez-Soler, R., Chachoua, A., Hammond, L.A., Rowinsky, E.K., Huberman, M., Karp, D., Rigas, J., Clark, G.M., Santabárbara, P. and Bonomi, P. (2004) Determinants of Tumor Response and Survival with Erlotinib in Patients with Non-Small-Cell Lung Cancer. Journal of Clinical Oncology, 22, 3238-3247. http://dx.doi.org/10.1200/JCO.2004.11.057

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.