Abstract:
Lung cancer is the leading cause of tumour-related death, in both sexes. Non-small cell lung cancer (NSCLC) represents the most frequent histological subtype including adenocarcinoma and squamous cell carcinoma. In the past decades, despite the development of new treatment options, five- and ten-years survival rates showed just little improvement and prognosis remained poor. Platinum-based chemotherapy represented the standard I line treatment for advanced disease, when histological testing showed no targetable genomic aberrations such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation or rearrangements and taxane-based chemotherapy was the best treatment options in second line, archiving a median overall survival (OS) of few months. The advent of immunotherapy has eventually changed outcomes of patients affected by NSCLC providing new and promising weapons. In particular, several agents modulating PD-1/PDL-1 pathway, demonstrated significant efficacy in prolonging NSCLC patients’ survival. Nivolumab, a PD-1 inhibitor, demonstrated to reduce by 40% the risk of death in NSCLC patients selected by histology, (Checkmate 017, for squamous carcinoma and Checkmate 057 for non-squamous carcinoma) in second line treatment, independently of PD-L1 expression. Pembrolizumab in monotherapy, another PD-1 inhibitor, reached survival improvement in NSCLC patients with positive PD-L1 expression, independently of histotype, both in first line for strong positive patients (Keynote 024) and in second line (Keynote 010). Recently Keynote-189 study, underlined a reduction of risk of death by 41% in non-squamous NSCLC patients treated with pembrolizumab in combination to platinum-based chemotherapy, independently of PDL1 expression. Two PD-L1 inhibitor have also been recently approved: atezolizumab in second line treatment independently of histotype and PD-L1 expression (OAK trial) and durvalumab for patients with stage III NSCLC whose disease did not progress after concomitant chemo-radiation therapy (PACIFIC trial), reaching a 18-month progression-free survival rate of 44.2% versus 27.0% On one hand, the outbreak of immunotherapy in NSCLC has revolutionized treatment and outcomes of NSCLC patients, encouraging research to proceed. On the other hand this new therapeutic frontier brought along a full baggage of unresolved questions. 17th SEP.2018, Monday - 10:20 Page 19 Oncology and Radiology 2nd International Conference on ICOR 2018 Despite the extraordinary efficacy of immunotherapy, only a fraction of patients actually benefits of such treatments and predictive factors to aid clinicians’ decision-making are still lacking. Identifying the right patient is becoming more and more important as new drugs are approved and combined treatments are under investigation. To achieve a true personalized medicine, focus has been pointed on molecular biomarkers that can predict a response to immune checkpoints. Moreover, immunotherapy functions through the regulation of immune system, causing a new landscape of adverse events. Immune-mediated adverse events include a range of dermatologic, pulmonary, gastrointestinal, endocrine, and hepatic toxicity. Multidisciplinary approach is extremely useful to face this new challenge in order to hasten diagnosis and prevent high-grade toxicity. The efficacy of innovative treatments is noteworthy, but their price is highly expensive. The continuous rise of cancer care costs (with the important contribute of immunotherapy in NSCLC) is becoming a real issue and it is to wonder until when health care systems will be able to afford it.
