Safety and efficacy of immune checkpoint blockade in patients with advanced nonsmall cell lung cancer and brain metastasis

Abstract

The presence of brain metastases (BM) is a negative prognostic factor for patients with advanced nonsmall cell lung cancer (NSCLC). Their incidence seems to be higher in patients with oncogene‐driven tumours, especially those with EGFR‐mutated or ALK‐rearranged tumours. Although targeted treatments demonstrate significant efficacy regarding BM, they only apply to a minority of NSCLC patients. On the other hand, systemic therapies for nononcogenic‐driven NSCLC with BM have shown limited clinical benefit. In recent years, immunotherapy alone or combined with chemotherapy has been adopted as a new standard of care in first‐line therapy. This approach seems to be beneficial to patients with BM in terms of efficacy and toxicity. Combined immune checkpoint inhibition as well as the combination of immunotherapy and radiation therapy show promising results with significant, but overall acceptable toxicity. A pragmatic approach of allowing enrolment of patients with untreated or symptomatic BM in randomised trials evaluating immune checkpoint inhibitors strategies, possibly coupled with central nervous system‐related endpoints may be needed to generate data to refine treatment for this patient population.

PD-1 blockade does not improve efficacy of EpCAM-directed CAR T-cells in lung cancer brain metastasis.

“…[29] While immune checkpoint inhibitors show promise in some cases, most patients do not respond to these therapies, emphasizing the need for new treatments. [30] Challenges in cellular-based approaches for solid brain tumors include the consistent identi cation of targets. [31] We used a fully immunocompetent murine model of lung cancer brain metastases and combined a chronic cranial window with repeated in vivo TPLSM to explore real-time dynamics of CAR T-cells at a single-cell level during combined administration of anti-PD1 and CAR T-cells.…”

Overall Survival after Radiotherapy for Brain Metastases According to ECOG Status—A Prospective Study of 294 NSCLC Patients

“…Over time, standard-of-care treatment for NSCLC BMs has changed, with more use of stereotactic radiotherapy (SRT) and new systemic treatments. Targeted therapies have intracerebral response rates of 40-80%, resulting in prolonged survival in patients with driver mutations [8], and there are limited but promising data on the effect of immunotherapy in NSCLC patients with BMs [9]. For patients with symptoms due to high intracerebral pressure or the need for a biopsy, surgery is still the recommended treatment, regardless of systemic therapy options [10].…”