Background: Genomic profiling in advanced Non-Small Cell Lung cancer (NSCLC) can reveal Actionable Molecular Alterations (AMAs). Our study aims to investigate clinical relevance of re-biopsy after first line treatment, by reporting on acquired and persistent AMAs and potential targeted treatments in a real-time cohort of NSCLC patients. Methods: Patients with advanced NSCLC receiving first-line treatment were prospectively included in an observational study (NCT03512847). Genomic profiling was performed by TruSight Oncology 500 HT gene panel on tumor tissue collected at diagnosis and at time of progression. Results: The 92 patients re-biopsied at progression had received immunotherapy (n = 44), chemotherapy (n = 44), or combination treatment (n = 4). In 87 of these patients (95%), successful genomic profiling was performed at both the diagnostic biopsy and the re-biopsy. In 74 patients (85%), ≥1 AMA were found. The AMAs were acquired in 28%. The most frequent AMAs were observed in TP53 (45%), KRAS (24%), PIK3CA (6%), and FGFR1 (6%). Only five patients (5%) received targeted treatment mainly due to deterioration in performance status. Conclusions: Re-biopsy at progression revealed acquired AMAs in approximately one third of patients, and 85% had at least one AMA with the potential of receiving targeted treatment, thus strengthening the clinical relevance of re-biopsy.
Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6-20.0) and 6% (95% CI 5.1-7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis.
