Safety and Efficacy of Racotumomab-Alum Vaccine as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer

Eduardo Santiesteban, Leslie Perez, Sailyn Alfonso, Elia Neninger, Soraida Acosta, Yoana Flores, Maurenis Hernandez, Carmen Viada, Robin García, Meylán Cepeda, Daymys Estevez, Yoisbel Moreno, Amparo Macías

Celestino Hernández Robau Hospital, Villa Clara, Cuba.
Center of Molecular Immunology, Havana, Cuba.
Hermanos Ameijeiras Hospital, Havana, Cuba.
José Ramón López Tabranes Hospital, Matanzas, Cuba.
National Institute of Oncology and Radiobiology, Havana, Cuba.
Saturnino Lora Hospital, Santiago de Cuba, Cuba.

DOI: 10.4236/ijcm.2014.514113                

Abstract

Despite extensive clinical research in non-small cell lung cancer (NSCLC), overall survival is still poor. Racotumomab-alum is an anti-idiotypic cancer vaccine that targets NeuGcGM3 tumor associated ganglioside. The aim of this study was to evaluate safety and efficacy of racotumomab-alum in advanced NSCLC patients with progressive disease. This expanded access program included 86 histologically confirmed NSCLC patients, 18 years or older age, with advanced disease and without therapeutic option, with ECOG performance status ≤3, adequate organ functions and signed informed consent. The primary endpoint was overall survival and toxicity was measure assessed treatment-related toxicity according CTCAEv3. The study was approved by ethical review boards of participant institutions. Racotumomab-alum treatment consisted in 5 biweekly intradermal doses (1 mg/mL) during the induction phase of treatment (2 months). The maintenance phase consisted in monthly re-immunizations until unacceptable toxicity or PS worsening. The median overall survival time of all patients treated with racotumomab-alum was 8.96 months. The survival rates at 12 and 24 months were 42.8% and 28.0%, respectively. Patients that completed the induction phase of treatment (five doses or more) reached a median OS of 12.1 months. The most common adverse events were injection site reaction, bone pain, cough and asthenia. Racotumomab-alum cancer vaccine could be considered an effective and safe treatment option as second-line therapy for advanced NSCLC. Further clinical studies should be conducted to confirm this result.

Keywords

Non-Small Cell Lung Cancer, Cancer Vaccine, Second-Line Treatment

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	American Cancer Society (2013) Cancer Facts & Figures 2013. American Cancer Society, Atlanta.
[2]	Public Health Ministry and National Medical Records (2013) Health Statistics Yearbook 2012. MINSAP, La Habana.
[3]	Finkelstein, D.M., Ettinger, D.S. and Ruckdeschel, J.C. (1986) Long-Term Survivors in Metastatic Non-Small-Cell Lung Cancer: An Eastern Cooperative Oncology Group Study. Journal of Clinical Oncology, 4, 702-709.
[4]	Howlader, N., Noone, A., Krapcho, M., et al. (2012) SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations) Based on November 2011 SEER Data Submission. National Cancer Institute, Bethesda.
[5]	Grossi, F., Gridelli, C., Aita, M. and De Marinis, F. (2008) Identifying an Optimum Treatment Strategy for Patients with Advanced Non-Small Cell Lung Cancer. Critical Reviews in Oncology/Hematology, 67, 16-26. http://dx.doi.org/10.1016/j.critrevonc.2007.12.002
[6]	Shepherd, F.A., Dancey, J., Ram Lau, R., Mattson, K., Gralla, R., O’Rouke, M., et al. (2000) Prospective Randomized Trial of Docetaxel versus Best Supportive Care in Patients with Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy. Journal of Clinical Oncology, 18, 2095-2103.
[7]	Hanna, N., Shepherd, F.A., Fossella, F.V., Pereira, J.R., De Marinis, F., von Pawel, J., et al. (2004) Randomized Phase III Trial of Pemetrexed versus Docetaxel in Patients with Non-Small Cell Lung Cancer Previously Treated with Chemotherapy. Journal of Clinical Oncology, 22, 1589-1597. http://dx.doi.org/10.1200/JCO.2004.08.163
[8]	Shepherd, F.A., Rodriguez Pereira, J., Ciuleanu, T., Tan, E.H., Hirsh, V., Thongprasert, S., et al. (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
[9]	Gridelli, C., de Marinis, F., Di Maio, M., Ardizzoni, A., Belani, C., Cappuzzo, F., et al. (2012) Maintenance Treatment of Advanced Non-Small Cell Lung Cancer: Results of an International Expert Panel Meeting of the Italian Association of Thoracic Oncology. Lung Cancer, 76, 269-279. http://dx.doi.org/10.1016/j.lungcan.2011.12.011
[10]	Irie, A. and Suzuki, A. (1998) CMP-Neu-Acetylneuraminic Acis Hydroxilase Is Exclusively Inactive in Humans. Biochemical and Biophysical Research Communications, 248, 330-333. http://dx.doi.org/10.1006/bbrc.1998.8946
[11]	Chou, H.H., Takematsu, H., Díaz, S., Iber, J., Nickerson, E., Wright, K.L., et al. (1998) A Mutation in Human CMP-Sialic Acid Hydroxylase Occurred after the Homo-Pan Divergence. Proceedings of the National Academy of Sciences of the United States of America, 95, 11751-11756. http://dx.doi.org/10.1073/pnas.95.20.11751
[12]	Hayashi, N., Chiba, H., Kuronuma, S., Go, S., Hasegawa, Y., Takahashi, M., et al. (2013) Detection of N-Glycolyated Gangliosides in Non-Small-Cell Lung Cancer Using GMR8 Monoclonal Antibody. Cancer Science, 104, 43-47. http://dx.doi.org/10.1111/cas.12027
[13]	Hernández, A.M., Rodríguez, M., López-Requena, A., Beausoleil, I., Pérez, R. and Vázquez, A.M. (2005) Generation of Anti-Neu-Glycolyl-Ganglioside Antibodies by Immunization with an Anti-Idiotype Monoclonal Antibody: A Self-versus Non-Self-Matter. Immunobiology, 210, 11-21. http://dx.doi.org/10.1016/j.imbio.2005.02.002
[14]	Alfonso, M., Diaz, A., Hernández, A.M., Pérez, A., Rodríguez, E., Bitton, R.J., et al. (2002) An Anti-Diotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients. Journal of Immunology, 168, 2523-2529. http://dx.doi.org/10.4049/jimmunol.168.5.2523
[15]	Díaz, A., Alfonso, M., Alonso, R., Saúrez, G., Troce, M., Catalá, M., et al. (2003) Immune Responses in Breast Cancer Patients Immunized with an Anti-Idiotype Antibody Mimicking NeuGc-Containing Gangliosides. Clinical Immunology, 107, 80-89. http://dx.doi.org/10.1016/S1521-6616(03)00036-6
[16]	Guthmann, M.D., Castro, M.A., Cinat, G., Venier, C., Koliren, L., Bitton, R.J., et al. (2006) Cellular and Humoral Immune Response to N-Glycolyl-GM3 Elicited by Prolonged Immunotherapy with an Anti-Idiotypic Vaccine in High Risk and Metastatic Breast Cancer Patients. Journal of Immunotherapy, 29, 215-223. http://dx.doi.org/10.1097/01.cji.0000188502.11348.34
[17]	Neninger, E., Diaz, R., de la Torre, A., Rives, R., Díaz, A. and Saúrez, G. (2007) Active Immunotherapy with 1E10 MAb Anti-Idiotype Vaccine in Patients with Small Cell Lung Cancer. Report of a Phase I Trial. Cancer Biology & Therapy, 6, e1-e6. http://dx.doi.org/10.4161/cbt.6.2.3574
[18]	Alfonso, S., Díaz, R., De la Torre, A., Santiesteban, E., Aguirre, F., Pérez, K., et al. (2007) 1E10 MAb Anti-Idiotypic Vaccine in Non-Small Cell Lung Cancer: Experience in Stage IIIB and IV Patients. Cancer Biology & Therapy, 6, 1-6. http://dx.doi.org/10.4161/cbt.6.12.5000
[19]	Alfonso, S., Valdés-Zayas, A., Santiesteban, E., Flores, I., Areces, F., Hernández, M., et al. (2014) A Randomized, Multicenter, Placebo-Controlled Clinical Trial of Racotumomab-Alum Vaccine as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer. Clinical Cancer Research, in Press. http://dx.doi.org/10.1158/1078-0432.CCR-13-1674
[20]	Giaccone, B.L., Nemunaitis, N., Juhasz, E., Ram Lau, R., van den Heuvel, M.M., et al. (2013) A Phase III Study of Belagenpumatucel-L Therapeutic Tumor Cell Vaccine for Non-Small Cell Lung Cancer (NSCLC). 17 European Cancer Congress 2013 Presidential Session I: Best and Late Breaking Abstracts, Abs 2.
[21]	Butts, C.A., Socinski, M.A., Mitchell, P., Thatcher, N., Havel, L., Krzakowski, M.J., et al. (2013) START: A Phase III Study of L-BLP25 Cancer Immunotherapy for Unresectable Stage III Non-Small Cell Lung Cancer. Journal of Clinical Oncology, 31, Abstract No. 7500).
[22]	Crombet, T., Acosta, S., Amador, R., Mendoza, S., Santiesteban, E., Rodriguez, C., et al. (2012) EGF-Based Cancer Vaccine for Advanced NSCLC: Results from a Phase III Trial. Journal of Clinical Oncology, 30, Abstract No. 2527.