The incidence of lung cancer has risen dramatically. It is already projected that near two million new lung cancer cases will occur in the United States resulting in approximately half a million fatal outcomes in 2018 (1). According to the data provided by the Centers for Disease Control and Prevention (CDC) lung cancer has been assessed as a second leading type of cancer in both men and women. Screening modalities of contemporary medicine have not yet addressed the issue of diagnosing lung cancer in early stages, resulting in capturing this condition as a progressive disease in most of the patients. Conventional treatment of non-small cell lung cancer (NSCLC) including surgery, chemotherapy, and radiotherapy has very limited efficacy in advanced stages of NSCLC and has been associated with serious toxicities. Additional problem represents cancer recurrence after conventional treatment occurring in approximately 40 percent of patients after a period of one year (2).
Cuba has produced 33 new drugs for treating cancer by the year 2012 (3). The fastgrowing medical scientific research in Cuba continues to produce innovative medicinal products, aiming to significantly increase the quality of life in patients suffering from most complex and serious medical conditions.
Cuba’s Advancements in the Treatment of Non-Small Cell Lung Cancer
An interesting and novel therapeutic approach that includes programming of body’s own immune system to fight cancer cells was investigated in Cuba. The research prompted the development of immune therapies including therapeutic vaccines. Vaxira is a therapeutic vaccine developed to treat NSCLC. The medicinal product was registered in Latin American countries in 2013, after promising results shown in phase II/III study involving patients with advanced and progressive NSCLC (4). In this study, patients that received Vaxira showed a significant increase in overall survival comparing to patients who received placebo. Another study that involved 180 patients investigated the effects of Vaxira following conventional treatment for late-stage, recurrent NSCLC. The results clearly showed decrease in the progression of NSCLC which directly resulted in prolonged survival periods in patients who previously received the first-line treatment for NSCLC (5). Finally, a randomized, open-label clinical trial that involved 1082 patients with advanced NSCLC, who received standard first-line therapy, showed the response of stable disease after administering Vaxira (6).
The safety profile of Vaxira was also evaluated in clinical trials described above. In a phase I study of Vaxira for NSCLC that was focused on patient safety, no serious adverse events that were considered to be related to treatment have occurred. Related events included local reactions at the administration site including pain, redness, and induration. Reactions were mild and reversible in nature (7). Toxicity in more advanced clinical trials of Vaxira was similar to those in the phase I study described above. Cases of a headache, joint pain, and fever were also observed, however, all events were mild to moderate in nature.
Vaxira was initially developed in Cuba. The well-recognized efficacy of this medicinal product in the treatment of NSCLC prompted multiple investigations for a wide variety of conditions including melanoma, breast, and lung cancer at different locations worldwide (Spain, Brasil, Singapore).
It has been recognized that malignant cells express epidermal growth factor (EGF) receptor in higher amounts than non-malignant cells. This particular characteristic of tumor cells enables them to grow more rapidly and spread more aggressively (8). CIMAvax-EGF vaccine expresses anti-cancer activity by stimulating the production of anti-EGF antibodies, which inactivate the circulating EGF directly inhibiting the proliferative nature of malignant tumor (9).
The effectiveness of CIMAvax-EGF was demonstrated in Phase II clinical trial, conducted in 80 patients with NSCLC, who were previously treated with standard platinum-based chemotherapy. Patients treated with CIMAvax-EGF showed increased survival trends (10). A Phase III open-label efficacy study that was conducted on the sample of 405 patients that suffered from a late-stage NSCLC showed a significant increase of 5-year survival in those who received the vaccine. The 5-year survival rate for vaccinated patients was approximately 16% in comparison to control group, where 5-year survival was 6% (11). Interestingly, it has been noted that following vaccination, levels of EGF remained low in patients with long-term survival (more than 2 years). EGF level proved to be a powerful prognostic factor for overall survival and cancer recurrence (12). CIMAvax-EGF can be administered concomitantly with standard platinum-based cytotoxic treatment for NSCLC. It is advised to administer the vaccine during or prior to platinum-based treatment in order to achieve the best possible response and efficacy (13).
The safety profile of CIMAvax-EGF was evaluated in the aforementioned clinical trials. The most frequent reactions associated with the use of CIMAvax-EGF were local administration site reactions including pain and redness, as well as systemic reactions such as fever, headache, chills, and shortness of breath. It is clear that the benefits of this vaccine outweigh the risks related to the administration of CIMAvax-EGF.
Due to the extensive therapeutic potential of CIMAvax-EGF, a Phase IV clinical trial was launched that enrolled more than 1000 patients with NSCLC (14). It was shown that the use of this vaccine is safe and beneficial to patients with NSCLC. Preliminary evidence suggested that besides the increase in overall survival, CIMAvax-EGF improved the quality of life of enrolled patients by increasing the emotional well-being and reducing symptoms and signs of fatigue.
This revolutionary medicinal product prompted new research focused on other types of cancers including prostate cancer and gave hope both to the scientific community and patients that the cure for NSCLC is on the horizon.
- Cancer statistics, 2018. Siegel RL, Miller KD, Jemal A. s.l. : CA Cancer J Clin, 2018, Vol. 68(1). 7.
- Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Sugimura H, Nichols FC, Yang P, Allen MS, Cassivi SD, Deschamps C, Williams BA, Pairolero PC.s.l. : Ann Thorac Surg, 2007, Vol. 83(2). 409.
- Profit vs health? Comparing the business models of Cuban and US pharma. Baden, Denise, Davies, Courtney and Wilkinson.s.l. : Monograph (Working Paper), Southampton, GB University of Southampton 12pp, 2015.
- A randomized, multicenter, placebo-controlled clinical trial of racotumomab-alum vaccine as switch maintenance therapy in advanced non-small cell lung cancer patients. Alfonso, S et al.s.l. : Clin Cancer Res, 2014, Vol. 20(14). 3660-71.
- Active immunotherapy in patients with progressive disease (PD) after first-line therapy. Gomez, R.E., Alfonso, S et al. s.l. : 49th Annu Meet Am Soc Clin Onco (ASCO), 2013. Abst 3086.
- Trial proactive: A prospective, randomized, multicenter, open label phase III study of active specific immunotherapy with racotumomab plus best support treatment versus best support treatment in patients with advanced non-small cell lung cancer. Roberto E Gomez, Amparo Macias, Tania Crombet, Ana Maria Vazquez et al. s.l. : Journal of Clinical Oncology.
- An anti-idiotype vaccine elicits a specific response to N-glycolyl sialic acid residues of glycoconjugates in melanoma patients. Alfonso, M et al. s.l. : J Immunol, 2002, Vol. 165(5). 2523-9.
- Molecular epidemiology of lung cancer and geographic variations with special reference to EGFR mutations. Mitsudomi, T. s.l. : Transl Lung Cancer Res, 2014, Vol. 3(4). 205-11.
- Clinical development and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer therapy. Rodríguez PC, Rodríguez G, González G, Lage A. s.l. : MEDICC Rev, 2010, Vol. 12(1). 17-23.
- Phase II randomized controlled trial of an epidermal growth factor vaccine in advanced non-small-cell lung cancer. Neninger Vinageras E, de la Torre A, Osorio Rodríguez M, Catalá Ferrer M, Bravo I, Mendoza del Pino M, Abreu Abreu D, Acosta Brooks S, Rives R, del Castillo Carrillo C, González Dueñas M, Viada C, García Verdecia B, Crombet Ramos T, González Marinello G. s.l. : J Clin Oncol, 2008, Vol. 26(9). 1452-8.
- A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients. Rodriguez, PC et al. s.l. : Clin Cancer Res, 2016, Vol. 22(15). 3782-90.
- Biomarkers related to immunosenescence: relationships with therapy and survival in lung cancer patients. Saavedra D, García B, Lorenzo-Luaces P, González A, Popa X, Fuentes KP, Mazorra Z, Crombet T, Neninger E, Lage A. s.l. : Cancer Immunol Immunother, 2016, Vol. 65(1). 37-45.
- Combining an EGF-based cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer. Neninger E, Verdecia BG, Crombet T, Viada C, Pereda S, Leonard I, Mazorra Z, Fleites G, González M, Wilkinson B, González G, Lage A. s.l. : J Immunother, 2009, Vol. 32(1). 92-9.
- CIMAvax EGF (EGF-P64K) vaccine for the treatment of non-small-cell lung cancer. Crombet Ramos T, Rodríguez PC, Neninger Vinageras E, Garcia Verdecia B, Lage Davila A. s.l. : Expert Rev Vaccines, 2015, Vol. 14(10). 1303-11.