ESMO E-Learning: First-Line Treatment of Non-Oncogene Addicted Advanced NSCLC

In this E-Learning module, the author lists the current options for upfront treatment in stage IV non-oncogene addicted non-small cell lung cancer (NSCLC) and illustrates them with findings from the clinical trials. The module reflects the recent change in practice; PD-(L)1 blockade, as mono-immunotherapy or combined with other anticancer agents, is now a routine part of the care of most patients with newly diagnosed metastatic NSCLC.

The author underlines that smoking cessation is highly encouraged.
Systemic therapy is offered to all patients with performance status (PS) 0–2. Treatment decisions in advanced NSCLC are based on histology and molecular pathology, age, PS, comorbidities and patients’ preferences.

Chemotherapy has been the only treatment option for patients with ECOG PS 0–, stage IV NSCLC for many years. The module provides considerations about the number of chemotherapy agents, type of chemotherapy regimen, as well as number of chemotherapy cycles.

In terms of chemotherapy choice, the author highlights the importance of the histologic subtype in NSCLC and elaborates the concept of maintenance therapy, as well as combination of chemotherapy plus anti-angiogenic therapy.

The Module provides a comprehensive overview of the results from clinical studies with chemotherapy and anti-EGFR antibodies, and an excellent overview of clinical studies with immune checkpoint inhibitors as monotherapy in first-line setting, immunotherapy plus chemotherapy in the first-line setting, as well as immunotherapy combinations.

In terms of immune checkpoint inhibitors, the module presents trials with PD(L)1 antibodies nivolumab, pembrolizumab, atezolizumab and durvalumab, as well as with CTLA-4 antibodies ipilimumab and tremelimumab. Furthermore, the author gives a summary of specific situations when to use PD(L)1 blockade or not in the first-line setting in terms of contraindications or special clinical concerns.

The module is supported by recommendations from the ESMO Clinical Practice Guidelines for the management of NSCLC and the statements are challenged with open questions about selecting the best strategy.

The author concludes that it is crucial to refine the predictive value of known biomarkers, as well as explore other biomarkers to better select patients to be treated with each potential strategy.