Immunotherapy in NSCLC: A Promising and Revolutionary Weapon

  • Christian Rolfo
  • Christian Caglevic
  • Mariacarmela Santarpia
  • Antonio Araujo
  • Elisa Giovannetti
  • Carolina Diaz Gallardo
  • Patrick Pauwels
  • Mauricio Mahave
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 995)


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.


Immunotherapy PDL1 PD1 NSCLC Immune checkpoints 



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


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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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Christian Rolfo
    • 1
    • 2
  • Christian Caglevic
    • 3
    • 4
  • Mariacarmela Santarpia
    • 5
  • Antonio Araujo
    • 6
  • Elisa Giovannetti
    • 7
  • Carolina Diaz Gallardo
    • 8
  • Patrick Pauwels
    • 9
  • Mauricio Mahave
    • 4
  1. 1.Phase I—Early Clinical Trials Unit, Oncology DepartmentUniversity Hospital AntwerpEdegemBelgium
  2. 2.Center or Oncological Research (CORE)Antwerp UniversityAntwerpBelgium
  3. 3.Department of Investigational Cancer Drugs, Medical Oncology DepartmentInstituto Oncológico Fundación Arturo López PérezSantiagoChile
  4. 4.Medical Oncology DepartmentInstituto Oncológico Fundación Arturo López PérezSantiagoChile
  5. 5.Medical Oncology Unit, Department of Human Pathology ‘G. Barresi’University of MessinaMessinaItaly
  6. 6.Medical Oncology DepartmentCentro Hospitalar do PortoPortoPortugal
  7. 7.Department of Medical OncologyVU University Medical CenterAmsterdamThe Netherlands
  8. 8.Immunology Unit, Internal Medicine ServiceClinicas Las CondesSantiagoChile
  9. 9.Molecular Pathology Unit, Pathology DepartmentAntwerp University HospitalEdegemBelgium

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