[First line treatment of non-oncogene-addicted metastatic non-small cell lung cancer]

Since 2017, anti-PD-(L)1 immunotherapy has been the cornerstone of first-line treatment for stage IV non-oncogene-addicted non-small cell lung cancer. Its phase I development has established that the level of PD-L1 expression by tumor cells is predictive of response rate and progression-free survival. Above 50%, it makes chemotherapy not mandatory, with a median survival for pembrolizumab monotherapy of around 26 months and five-year survival of 32%. Large phase III studies have also validated the combination of anti-PD-(L)1 immunotherapy and platinum-based chemotherapy regardless of PD-L1 level of expression, increasing five-year survival from 10% to 18%. Dual immunotherapy combining anti-CTLA-4 and anti-PD-(L)1 might be interesting, especially in PD-L1 negative tumors, but is not available in France. Treatment personalization, particularly in the case of PD-L 1 expression >50%, should be based on response and non-response factors to immunotherapy, including patient-related factors such as performans status, age, smoking status, as well as tumor-related factors such as disease aggressiveness, tumor volume, mutational profile, along with concomitant medications. The optimal duration of immunotherapy is uncertain and arbitrarily set at two years. Many options are currently being explored to improve first-line treatment outcomes, as the majority of patients experience resistance to immunotherapy.