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Immunotherapy in NSCLC: A Promising and Revolutionary Weapon

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Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 995))

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Abstract

Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status.

Immunotherapy recently has become the most revolutionary treatment in solid tumors patients. First results in unresectable and metastatic melanoma patients treated with an anti CTLA-4 monoclonal antibody showed an unexpected 3-year overall survival of at least 25%.

Lung cancer cells have multiple immunosuppressive mechanisms that allow to escape of the immune system and survive, however blocking CTLA-4 pathway with antibodies as monotherapy treatment have not achieved same results than in melanoma patients. PD-1 expression has been demonstrated in different tumor types, suggesting than PD-1 / PD-L1 pathway is a common mechanism used by tumors to avoid immune surveillance and favoring tumor growth. Anti PD-1 and anti PD-L1 antibodies have showed activity in non-small cell lung cancer patients with significant benefit in overall survival, long lasting responses and good safety profile, including naïve and pretreated patients regardless of the histological subtype. Even more, PD-1 negative expression patients achieve similar results in overall survival when compared with patients treated with chemotherapy. In the other side high PD-1 expression patients that undergo immunotherapy treatment achieve better results in terms of survival with lesser toxicity. Combining different immunotherapy treatments, combination of immunotherapy with chemotherapy or with targeted treatment are under research with some promising PRELIMINARY results in non-small cell lung cancer patients.

This chapter attempts to summarize the development of immunotherapy treatment in non-small cell lung cancer patients and explain the results that have leaded immunotherapy as a new standard of treatment in selected NSCLC patients.

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Acknowledgments

Thanks to Dr. Rodolfo Mauceri for his contribution for the images for this chapter.

Disclosures

Authors declare not commercial funding, not honoraria for this manuscript and not participation direct or indirectly by pharmaceutical industry.

Authors declare personal disclosures that could be considered of interest regarding the content of the chapter.

Christian Rolfo: Novartis speaker bureau, Mylan scientific advisor, Sanfo research grant, Precision Medicine: Steering committee.

Christian Caglevic: Principal investigator for clinical trials in NSCLC with immunotherapy drugs (MSD, AZ) and subinvestigator (BMS). Speaker (BMS and MSD), Advisory board (MSD–AZ), Consultant (BMS–MSD), Courses and transportation financial (BMS)

María Carmela Santarpia: not disclosures.

Antonio Araujo: not disclosures.

Elisa Giovannetti: not disclosures.

Carolina Díaz Gallardo: not disclosures.

Patrick Pauwels: not disclosures.

Mauricio Mahave: not disclosures.

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    Authors and Affiliations

    1. Phase I—Early Clinical Trials Unit, Oncology Department, University Hospital Antwerp, Edegem, Belgium

      Christian Rolfo M.D., Ph.D., M.B.Ah

    2. Center or Oncological Research (CORE), Antwerp University, Antwerp, Belgium

      Christian Rolfo M.D., Ph.D., M.B.Ah

    3. Department of Investigational Cancer Drugs, Medical Oncology Department, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile

      Christian Caglevic M.D.

    4. Medical Oncology Department, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile

      Christian Caglevic M.D. & Mauricio Mahave M.D.

    5. Medical Oncology Unit, Department of Human Pathology ‘G. Barresi’, University of Messina, Messina, Italy

      Mariacarmela Santarpia M.D.

    6. Medical Oncology Department, Centro Hospitalar do Porto, Porto, Portugal

      Antonio Araujo M.D., Ph.D.

    7. Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands

      Elisa Giovannetti M.D., Ph.D.

    8. Immunology Unit, Internal Medicine Service, Clinicas Las Condes, Santiago, Chile

      Carolina Diaz Gallardo M.D.

    9. Molecular Pathology Unit, Pathology Department, Antwerp University Hospital, Edegem, Belgium

      Patrick Pauwels M.D., Ph.D.

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    Correspondence to Christian Rolfo M.D., Ph.D., M.B.Ah .

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    Editors and Affiliations

    1. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

      Aung Naing

    2. Baylor College of Medicine-Texas Children’s Hospital, Houston, Texas, USA

      Joud Hajjar

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    Rolfo, C. et al. (2017). Immunotherapy in NSCLC: A Promising and Revolutionary Weapon. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 995. Springer, Cham. https://doi.org/10.1007/978-3-319-53156-4_5

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