Immunotherapy in NSCLC: A Promising and Revolutionary Weapon.
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.
Phase I-Early Clinical Trials Unit, Oncology Department, University Hospital Antwerp, Edegem, Belgium. christian.rolfo@uza.be.|Center or Oncological Research (CORE), Antwerp University, Antwerp, Belgium. christian.rolfo@uza.be.
Christian
C
Rolfo
Department of Investigational Cancer Drugs, Medical Oncology Department, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile.|Medical Oncology Department, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile.
Christian
C
Caglevic
Medical Oncology Unit, Department of Human Pathology 'G. Barresi', University of Messina, Messina, Italy.
Mariacarmela
M
Santarpia
Medical Oncology Department, Centro Hospitalar do Porto, Porto, Portugal.
Antonio
A
Araujo
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Elisa
E
Giovannetti
Immunology Unit, Internal Medicine Service, Clinicas Las Condes, Santiago, Chile.
Carolina Diaz
CD
Gallardo
Molecular Pathology Unit, Pathology Department, Antwerp University Hospital, Edegem, Belgium.
Patrick
P
Pauwels
Medical Oncology Department, Instituto Oncológico Fundación Arturo López Pérez, Santiago, Chile.
Mauricio
M
Mahave
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
Immune checkpoints; Immunotherapy; NSCLC; PD1; PDL1