Actionable Molecular Alterations Are Revealed in Majority of Advanced Non-Small Cell Lung Cancer Patients by Genomic Tumor Profiling at Progression after First Line Treatment

SIMPLE SUMMARY: In precision medicine, cancer patients are treated with drugs that target specific molecular alterations found in their cancer cells. As new drugs for specific targets emerge, possibilities expand. Our prospective clinical study explored the possibilities of receiving targeted treatments after standard first line treatment by performing genomic profiling of a biopsy taken at diagnosis, as well as at time of progression, in patients with advanced non-small cell lung cancer. In the majority of patients (85%), there was a potential of receiving targeted treatment, based on the re-biopsy results. In approximately one third of patients, we found new molecular alterations not present at the diagnostic biopsy, strengthening the relevance of performing a re-biopsy at progression to increase targeted treatment options, and hopefully bettering the prognosis. ABSTRACT: 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.