Cisplatin (CIS) Administered As Dry Powder for Inhalation (DPI) in Patients with Stage IV Non-Small Cell Lung Cancer

The combination of chemotherapy and immunotherapy shows promising results in terms of overall survival (OS) and progression-free survival (PFS) for the treatment of first-line stage IV non-small cell lung cancer (NSCLC) patients, leading to such combinations becoming a real backbone of the Standard of Care (SoC) for NSCLC patients. However, conventional chemotherapy's severe systemic toxicities represent a limiting factor in terms of administered dose and frequency. Administration of cisplatin by inhalation (pulmonary route) is a promising additional approach that may overcome the limitations of conventional chemotherapy. Use of a dry powder inhaler enables a high therapeutic response by delivering high local concentrations of a well-established active substance without the usual undesired reactions that limit the use of high doses when administered through the conventional systemic route. This study may provide insights into whether this add-on treatment might be a safe and potentially efficacious option for NSCLC patients.

The survival of patients with metastatic lung cancer has significantly improved with platinum-based treatments and, more recently, with targeted therapies and immunotherapies. However, despite therapeutic advances, lung cancer remains the world's leading cause of cancer-related death (approximately 2 million per year), due to innate or acquired tumour resistance to treatments. The combination of chemotherapy (platinum-doublets) and immunotherapy (immune checkpoint inhibitors) shows promising results in terms of overall survival (OS) and progression-free survival (PFS) for the treatment of first-line stage IV non-small cell lung cancer (NSCLC) patients, leading to such combinations becoming a real backbone of the Standard of Care (SoC) for NSCLC patients. These results may be attributable to the immunogenic effects of chemotherapy-induced tumour cell death, which, when used with immune checkpoint inhibitors, is an approach that may improve the clinical outcomes of cancer patients. However, conventional chemotherapy's severe systemic toxicities represent a limiting factor in terms of administered dose and frequency, requiring long rest phases (i.e., interruption of treatment) leading to a relatively limited frequency of chemotherapy treatment in current clinical practice (4 to 6 cycles of intravenous (iv) administration, all separated by a 3-week interruption period). This limitation, associated with high mortality, especially in the advanced stages of lung cancer, demonstrates that the treatments/combinations currently used are far from optimal. Administration of cisplatin by inhalation (pulmonary route) is a promising additional approach that may overcome the limitations of conventional chemotherapy and increase the efficacy of the current SoC via sustained local attack on the lung tumours of patients treated using immune checkpoint inhibitors with or without iv chemotherapy. Use of a dry powder inhaler (DPI) enables a high therapeutic response by delivering high local concentrations of a well-established active substance without the usual undesired reactions that limit the use of high doses when administered through the conventional systemic route. Thanks to limited systemic exposure to the cytotoxic active ingredient with the use of a dry powder inhaler, such add-on treatment enables considering 5 times weekly administration of inhaled chemotherapy at the patient's home. Increasing the frequency of local chemotherapy treatment in this way may enhance activation of the systemic anti-tumour immune response via local activation and stimulation of tumour-specific antigen release as a result of a safe, sustained and prolonged local effect, compared to the peak/short effect of iv chemotherapy. This study may provide insights into whether this add-on treatment might be a safe option for NSCLC patients.