Immunotherapy: From Advanced NSCLC to Early Stages, an Evolving Concept

Abstract

Immunotherapy in lung cancer treatment is a long history paved with failures and some successes. During the last decade, the discovery of checkpoints inhibitors led to major advances in treating advanced and metastatic non-small cell lung cancer (NSCLC). Impressive data from early phase I-II studies were subsequently confirmed in large prospective randomized trials and meta-analyses (High-level of evidence). Three anti-programmed death-1 (PD1) (pembrolizumab, nivolumab) or antiPD-ligand(L)1 (atezolizumab) antibodies showed clinically significant improved survival compared to second-line docetaxel. Then, first-line pembrolizumab monotherapy demonstrated its superiority over platinum-doublet in high PD-L1 NSCLC. The addition of pembrolizumab or atezolizumab to chemotherapy derived the same results regardless of the PD-L1 status. On the opposite, antiCTLA4 (Cytotoxic T-Lymphocyte Associated 4) results are currently disappointing in unselected patients while recent development suggest that the combination of antiPD1 and antiCTLA4 (nivolumab-ipilimumab) positively impact on overall survival. Some secondary analyses also showed that immunotherapy has a positive impact on quality of life and that the clinical improvement can be done at an acceptable incremental cost per QALY. A lot of questions remain unresolved: which is the best treatment duration and is it the same for all patients, how to choose the patients that will have the highest benefit of immunotherapy, how to identify the patients who will have rapid progression, how to improve the current data (new targets, new combinations)…

Relevance of PD-L1 Non-Coding Polymorphisms on the Prognosis of a Genetically Admixed NSCLC Cohort

“…NSCLC is a grim disease that is aggravated by the fact that patients normally either receive their diagnosis at advanced stages or present with recurrent disease after initial locoregional treatment. 2 Over the last few decades, conventional chemotherapy, mainly platinum-based chemotherapy, used to be the only therapeutic option for those not eligible for radical intent treatment: a treatment with limited efficacy and very few long-term survivors (5-year overall survival less than 15%). Furthermore, these patients often lacked therapeutic options beyond first-line treatment.…”

Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy

“…Despite substantial improvements in survival rates achieved by therapeutic advances in solid tumors since 1975, in the case of lung cancer, platinum-based chemotherapy has been the only therapeutic option with limited benefit on OS and very few long-term survivors [ 59 ]. Thus, the 5-year OS is only ~5% for patients with metastatic NSCLC, and between 20–25% or 2% for SCLC, depending on the extent of the disease.…”

Immunothérapie et tumeurs oligométastatiques

“…Les études de phase III ont confirmé l'activité très significativement meilleure en termes de survie du nivolumab, du pembrolizumab ou de l'atézolizumab en monothérapie comme traitement de rattrapage puis de ces mêmes molécules en première ligne métastatique, seules ou en combinaison (avec la chimiothérapie ou en doublet avec un antiCTLA4), par rapport à la chimiothérapie conventionnelle. Le but de cet article n'étant pas de revoir en détail l'activité de l'immunothérapie dans les CBNPC de stade IV, nous proposons au lecteur de se référer à une revue systématique publiée par l'auteur en 2019 [7].…”

“…Un nouvel intérêt pour l'immuno thérapie est survenu lors de la découverte des inhibiteurs des points de contrôle du système immunitaire « Cytotoxic T-Lymphocyte Associated 4 » (CTLA4) et « Programmed Death-1 (PD1)/ Programmed Death-Ligand 1 (PDL1) » [5,6]. Depuis lors, de multiples études randomisées ont confirmé, dans les CBNPC métastatiques, l'activité majeure d'anticorps monoclonaux dirigés contre ces cibles, essentiellement les antiPD1/ PDL1 seuls ou en association avec la chimiothérapie [7]. Actuellement, nous disposons en clinique de deux anticorps antiPD1, le nivolumab et le pembrolizumab, et de deux anticorps antiPD-L1, l'atézolizumab et le durvalumab, l'indication de ce dernier étant limitée aux cancers locorégionaux en adjuvant après une radio-chimiothérapie concomitante.…”